Disitamab Vedotin (RC48): A Comprehensive Analysis of a Novel HER2-Targeted Antibody-Drug Conjugate

Executive Summary

Disitamab vedotin (also known as RC48 and marketed as Aidixi®) is a novel, investigational antibody-drug conjugate (ADC) poised to make a significant impact on the treatment landscape for human epidermal growth factor receptor 2 (HER2)-expressing cancers. Developed by RemeGen and now a key asset in Pfizer's oncology portfolio following its acquisition of Seagen, disitamab vedotin is distinguished by its unique molecular design. It combines a novel anti-HER2 monoclonal antibody, hertuzumab, which binds to a distinct epitope with higher affinity than trastuzumab, with the potent microtubule inhibitor monomethyl auristatin E (MMAE) via a cleavable linker. This construction facilitates a powerful bystander effect, enabling the treatment of tumors with heterogeneous or low levels of HER2 expression.

Extensive clinical trials have demonstrated robust and clinically meaningful efficacy across multiple solid tumors. In urothelial carcinoma, disitamab vedotin has shown a 50.5% objective response rate (ORR) as a monotherapy in heavily pretreated patients and an impressive 73.2% ORR with a median overall survival (OS) of 33.1 months when combined with a PD-1 inhibitor. In gastric cancer, it is the first HER2-targeted therapy to show significant activity in the HER2-low population, a large and underserved segment. In breast cancer, disitamab vedotin has proven effective in both HER2-positive and HER2-low settings and shows promise in preclinical models resistant to the current standard-of-care, trastuzumab deruxtecan (Enhertu).

Critically, disitamab vedotin exhibits a manageable safety profile, with the most common grade ≥3 adverse events being peripheral sensory neuropathy and neutropenia. Its favorable profile concerning interstitial lung disease (ILD) presents a significant potential safety advantage over Enhertu, a key competitor.

The strategic journey of disitamab vedotin, from its development in China by RemeGen to its high-value licensing by Seagen and subsequent acquisition by Pfizer, highlights a new paradigm in global pharmaceutical development. With strong clinical data, a differentiated mechanism, and the backing of a global pharmaceutical leader, disitamab vedotin is strategically positioned to become a new standard of care in urothelial cancer and a vital therapeutic option for gastric and breast cancer, particularly in the HER2-low and treatment-resistant settings.

---

I. Introduction to Disitamab Vedotin: A New Entrant in the HER2-Targeted ADC Arena

The field of oncology has been revolutionized by the advent of precision medicine, which seeks to target the specific molecular drivers of cancer. Among the most successful classes of precision therapies are antibody-drug conjugates (ADCs). ADCs function as "biological missiles," combining the tumor-targeting specificity of a monoclonal antibody with the potent cell-killing power of a cytotoxic payload, connected by a chemical linker.[1] This approach allows for the selective delivery of chemotherapy to cancer cells, maximizing efficacy while minimizing the systemic toxicity associated with traditional chemotherapy.[3] The ADC modality is now a transformative and rapidly expanding therapeutic class in cancer treatment.[6]

Human Epidermal Growth Factor Receptor 2 (HER2) as a Validated Therapeutic Target

One of the most well-validated targets in oncology is the human epidermal growth factor receptor 2 (HER2, also known as ERBB2). HER2 is a receptor tyrosine kinase that, when overexpressed, promotes aggressive cell proliferation, survival, and metastasis.[7] It is a key oncogenic driver in a significant subset of breast, gastric, urothelial, and other solid tumors.[9] The development of HER2-targeted therapies, beginning with the monoclonal antibody trastuzumab, has dramatically improved outcomes for patients with HER2-positive cancers.[7] This success has spurred the development of next-generation therapies, including more advanced ADCs designed to overcome resistance and expand the treatable patient population.[11]

Disitamab Vedotin: Core Identifying Information and Development Genesis

Disitamab vedotin (DrugBank ID: DB17208) is a novel, investigational HER2-targeted ADC at the forefront of this next wave of innovation.[7] Also known by its research code RC48 and its trade name in China, Aidixi®, this biotech therapeutic was originally developed by the Chinese biopharmaceutical company RemeGen.[14] It has demonstrated significant antitumor activity in clinical trials across several solid tumor types, including urothelial carcinoma, gastric cancer, and breast cancer, positioning it as a major new entrant in the HER2-targeted therapy landscape.[17]

Table 1: Disitamab Vedotin - Key Drug Identifiers

Attribute	Value
Name	Disitamab vedotin
Alternative Names	RC48, Aidixi®
DrugBank ID	DB17208
Type	Biotech, Antibody-Drug Conjugate
CAS Number	2136633-23-1
Originator	RemeGen Co., Ltd.
Global Developer	Pfizer Inc. (via Seagen acquisition)

---

II. Molecular Profile and Differentiated Mechanism of Action

Disitamab vedotin is a complex biologic composed of three distinct components: a novel monoclonal antibody, a cytotoxic payload, and a specialized linker. The unique properties of each component contribute to a differentiated mechanism of action that sets it apart from other HER2-targeted ADCs.

The Antibody Component: A Novel Anti-HER2 Monoclonal Antibody (Hertuzumab)

Unlike first- and second-generation HER2 ADCs such as trastuzumab emtansine (T-DM1, Kadcyla) and trastuzumab deruxtecan (T-DXd, Enhertu), which utilize the well-established antibody trastuzumab, disitamab vedotin employs a novel, humanized IgG1 monoclonal antibody known as hertuzumab.[8] While some early reports referred to the antibody as trastuzumab [9], detailed molecular analyses have confirmed its unique identity.

This distinction is critical for two primary reasons:

1. Distinct Binding Epitope: Hertuzumab binds to a different epitope on subdomain IV of the HER2 extracellular domain compared to trastuzumab.[10] This alternate binding site may allow disitamab vedotin to be effective against tumors that have developed resistance to trastuzumab-based therapies through modifications at the trastuzumab binding site.
2. Higher Affinity and Enhanced Internalization: Preclinical models have consistently shown that hertuzumab exhibits a higher binding affinity for the HER2 receptor and a more rapid rate of internalization into the cancer cell compared to trastuzumab.[14] A faster internalization rate is crucial for an ADC, as it can lead to more efficient delivery of the cytotoxic payload to the intracellular machinery, potentially enhancing the drug's overall potency.

The Linker-Payload System: A Cleavable Linker and Monomethyl Auristatin E (MMAE)

The therapeutic effect of disitamab vedotin is delivered by its linker-payload system, which is designed for stability in circulation and potent, targeted cell killing.

• Cytotoxic Payload: The warhead of the ADC is monomethyl auristatin E (MMAE), a highly potent synthetic antineoplastic agent.[7] Once released inside the cancer cell, MMAE functions as a microtubule-disrupting agent. It binds to tubulin and inhibits its polymerization, which is essential for forming the mitotic spindle. This disruption halts the cell cycle in the G2/M phase, ultimately leading to programmed cell death, or apoptosis.[9]
• Protease-Cleavable Linker: The MMAE payload is attached to the hertuzumab antibody via a maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PABC) linker.[10] This linker is specifically designed to be stable in the bloodstream, preventing premature release of the toxic payload and minimizing off-target toxicity. However, upon internalization of the ADC into the cancer cell's lysosomes, the valine-citrulline (vc) component is recognized and cleaved by lysosomal proteases, such as cathepsin B, which are often upregulated in the tumor microenvironment. This precise cleavage mechanism ensures that the MMAE payload is released preferentially inside the target cancer cells.[8]

The Bystander Effect: A Key Differentiator for Treating Heterogeneous Tumors

A critical feature of disitamab vedotin, enabled by its cleavable linker and the membrane-permeable nature of MMAE, is its ability to induce a potent bystander effect.[13] After being released within a targeted HER2-positive cell, the MMAE payload can diffuse through the cell membrane into the surrounding tumor microenvironment. There, it can be taken up by adjacent cancer cells and exert its cytotoxic effect, even if those neighboring cells have low or no HER2 expression.[12]

This bystander killing mechanism is of profound clinical importance. Solid tumors are often heterogeneous, consisting of a mixed population of cells with varying levels of target antigen expression. Therapies that can only kill antigen-positive cells may leave behind a population of antigen-low or -negative cells, leading to tumor relapse and treatment resistance. By eliminating these neighboring cells, the bystander effect of disitamab vedotin can overcome tumor heterogeneity, leading to a more comprehensive and durable antitumor response.[28]

The molecular architecture of disitamab vedotin provides a dual strategy to combat therapeutic resistance. First, the use of a novel antibody targeting a distinct HER2 epitope may circumvent resistance mechanisms related to alterations in the trastuzumab binding site. Second, the potent bystander effect directly addresses the challenge of tumor heterogeneity, a common cause of treatment failure for many targeted therapies. This combination of a unique targeting moiety and a payload capable of broad, localized killing forms the foundation of the drug's therapeutic potential, particularly in later-line settings where resistance to prior treatments is common.

Drug-to-Antibody Ratio (DAR) and Its Impact on Therapeutic Index

The drug-to-antibody ratio (DAR) refers to the average number of payload molecules attached to each antibody. This is a critical quality attribute for any ADC, as it directly influences the balance between efficacy and toxicity. Disitamab vedotin has been engineered with a DAR of approximately 4.[26] This contrasts with a key competitor, Enhertu, which has a higher DAR of approximately 8.[25] While a higher DAR can deliver more cytotoxic payload per antibody and potentially increase potency, it can also negatively affect the ADC's pharmacokinetics, stability, and tolerability.[25] The selection of a DAR of 4 for disitamab vedotin represents a balanced approach, aiming to achieve a robust therapeutic window with significant antitumor activity and a manageable safety profile.

The choice of an MMAE payload, while proven effective, also places disitamab vedotin within a well-characterized class of ADCs. Resistance to MMAE, often through the upregulation of drug efflux pumps like ABCB1 (MDR1), is a known clinical challenge.[33] This is distinct from the resistance mechanisms associated with topoisomerase I inhibitors, the payload class used in Enhertu.[35] This fundamental difference in payload creates a non-cross-resistant paradigm and suggests that the future of HER2-targeted therapy will likely involve the strategic sequencing of ADCs with different payloads to overcome acquired resistance. A patient who progresses on an MMAE-based ADC may still be sensitive to a topoisomerase-based ADC, and vice versa, creating a clear rationale for their sequential use in the clinic.

---

III. Clinical Development and Efficacy in Urothelial Carcinoma (UC)

The most advanced global development program for disitamab vedotin is in urothelial carcinoma, where it has demonstrated compelling efficacy both as a monotherapy and in combination with immunotherapy, establishing its potential to significantly alter the treatment landscape.

Monotherapy in Previously Treated Patients: Combined Analysis of RC48-C005 & RC48-C009

The foundation of disitamab vedotin's clinical profile in UC was built upon two single-arm, multicenter, Phase II trials conducted in China: RC48-C005 (NCT03507166) and RC48-C009 (NCT03809013).[36] These studies enrolled patients with HER2-positive (defined as IHC 2+ or 3+) locally advanced or metastatic UC who had progressed after at least one line of systemic chemotherapy. The initial positive results from RC48-C005 led to its early termination and the initiation of RC48-C009 as a confirmatory study, with a combined analysis required by Chinese regulatory authorities.[37]

The combined analysis, encompassing 107 patients, yielded robust efficacy data that led to regulatory approvals in China and a Breakthrough Therapy Designation from the U.S. FDA.[39] With a median follow-up of 19.1 months, the key results were [36]:

• Objective Response Rate (ORR): The confirmed ORR, assessed by a blinded independent review committee (BIRC), was 50.5% (95% CI: 40.6%, 60.3%).
• Progression-Free Survival (PFS): The median PFS was 5.9 months (95% CI: 4.2, 7.2).
• Overall Survival (OS): The median OS was 14.2 months (95% CI: 9.7, 18.8).

These outcomes are particularly noteworthy given the heavily pretreated patient population, with 64.5% having received two or more prior lines of systemic chemotherapy.[36] Efficacy was consistent across key subgroups, including patients with visceral metastases and those with the most difficult-to-treat liver metastases, who achieved a cORR of 52.1%.[36] Importantly, the treatment was also effective in patients who had previously received PD-1/L1 inhibitors, with a cORR of 55.6% in this subgroup, indicating its activity in an immunotherapy-refractory setting.[36]

Table 3: Summary of Efficacy Results from Key Clinical Trials in Urothelial Carcinoma

Trial ID	Treatment Regimen	Patient Population (Line of Therapy)	N	Objective Response Rate (ORR)	Median Progression-Free Survival (PFS)	Median Overall Survival (OS)
RC48-C005/C009 (Combined) 36	Disitamab Vedotin (Monotherapy)	Previously Treated (≥1 line)	107	50.5%	5.9 months	14.2 months
RC48-C014 (Phase 1b/2) 42	Disitamab Vedotin + Toripalimab	Previously Treated / Treatment-Naïve	41	73.2%	9.3 months	33.1 months
RC48-C016 (Phase 3 Interim) 43	Disitamab Vedotin + Toripalimab	Treatment-Naïve (First-Line)	N/A	Statistically significant improvement vs. chemotherapy	Statistically significant improvement vs. chemotherapy	Statistically significant improvement vs. chemotherapy

Combination with PD-1 Inhibition: A Paradigm-Shifting Approach

Building on the strong monotherapy data, the combination of disitamab vedotin with PD-1 inhibitors has produced exceptional results, suggesting a synergistic interaction that could redefine the standard of care.

The investigator-initiated Phase Ib/II RC48-C014 trial (NCT04264936) evaluated disitamab vedotin in combination with the PD-1 inhibitor toripalimab in patients with HER2-expressing la/mUC.[42] Long-term follow-up data presented in January 2025 were remarkable, showing an

ORR of 73.2% and a median OS of 33.1 months.[42] This level of efficacy is superior to that reported in other prospective trials of ADC plus PD-1 combinations in this disease setting.[42] The observed benefit was durable, with a 36-month OS rate of 49.2%.[42]

The significant leap in efficacy from monotherapy (50.5% ORR) to combination therapy (73.2% ORR) points toward a synergistic, rather than merely additive, effect. This synergy is likely driven by the biological mechanism of the vedotin payload. MMAE is known to induce immunogenic cell death (ICD), a process where dying cancer cells release tumor antigens and danger signals that activate an immune response.[14] This "inflames" the tumor microenvironment, making it more visible and susceptible to the action of a PD-1 inhibitor, which in turn "releases the brakes" on the T-cells that infiltrate the tumor.

These promising results prompted the initiation of the pivotal, randomized Phase III RC48-C016 trial (NCT05302284), which compares the disitamab vedotin and toripalimab combination against standard platinum-based chemotherapy as a first-line treatment for HER2-expressing la/mUC.[45] In May 2025, RemeGen announced that a prespecified interim analysis of this trial met its dual primary endpoints, with the combination demonstrating statistically significant and clinically meaningful improvements in both PFS and OS compared to chemotherapy.[43]

Efficacy Across the HER2 Spectrum and Patient-Reported Outcomes

A key finding from the combination studies is the broad activity of disitamab vedotin across the full spectrum of HER2 expression. In the RC48-C014 trial, high ORRs were observed in patients with HER2 IHC 3+ (80.0%), IHC 2+ (84.2%), and even IHC 1+ (64.3%) expression.[42] This confirms that the drug's benefit is not limited to patients with high HER2 overexpression and significantly expands its potential patient population.

While detailed patient-reported outcome (PRO) data from instruments like the EORTC QLQ-C30 have not yet been published for the disitamab vedotin trials [49], quality of life is a key secondary endpoint in ongoing global studies like SGNDV-001 (NCT05911295).[52] The demonstrated superiority over chemotherapy, coupled with a manageable safety profile, strongly suggests that the combination regimen will lead to substantial improvements in patient quality of life by providing a more effective and better-tolerated alternative to cytotoxic chemotherapy.[54]

---

IV. Clinical Development and Efficacy in Gastric & Gastroesophageal Junction (GEJ) Cancer

Disitamab vedotin has also established a strong clinical footprint in gastric and gastroesophageal junction (GEJ) cancer, achieving regulatory approval in China and demonstrating groundbreaking efficacy in the HER2-low patient population.

Monotherapy in Heavily Pretreated Patients: The RC48-C008 Trial and NMPA Approval

The initial regulatory success for disitamab vedotin came from the RC48-C008 trial (NCT03556345), a single-arm, Phase II study in patients with HER2-positive advanced gastric or GEJ cancer who had failed at least two prior lines of systemic therapy.[16] In this heavily pretreated population with limited options, disitamab vedotin monotherapy demonstrated clinically meaningful activity.[30]

Based on data from 127 patients, the trial reported [16]:

• An investigator-assessed confirmed ORR of 18.1% (95% CI: 11.8%, 25.9%).
• A median OS of 7.6 months (95% CI: 6.6, 9.2).
• A median PFS of 3.8 months (95% CI: 2.7, 4.0).

These results led to the conditional approval of disitamab vedotin by China's National Medical Products Administration (NMPA) in 2021 for this indication, making it the first domestically developed ADC to win marketing approval in China.[16]

Combination Strategies and Expansion into the HER2-Low Population

Subsequent research has focused on moving disitamab vedotin into earlier lines of therapy and, critically, exploring its activity in patients with lower levels of HER2 expression. A Phase 2/3 platform study (NCT05980481) is evaluating various combinations in the first-line setting.[58]

The most significant findings from this study have come from the cohort of patients with HER2-low expressing tumors (defined as IHC 1+ or IHC 2+/ISH-). This is a large patient population for which no HER2-targeted therapies are currently approved.[61] In this cohort, the triplet combination of disitamab vedotin, toripalimab (PD-1 inhibitor), and CAPOX chemotherapy achieved an impressive

ORR of 72.0%. This was substantially higher than the 47.8% ORR seen in the control arm of toripalimab plus CAPOX.[60] This result represents a potential breakthrough, suggesting that disitamab vedotin could be the first therapy to successfully target the HER2-low gastric cancer population. The efficacy in this setting is likely driven by the high affinity of its novel antibody and the potent bystander effect of the MMAE payload, which allow for effective cell killing even when the density of the HER2 target is low.

In the HER2-overexpressing cohort of the same study, the combination of disitamab vedotin, toripalimab, and trastuzumab achieved a remarkable ORR of 82.4%, numerically superior to the 68.8% ORR in the control arm, suggesting a powerful synergistic effect of dual HER2 blockade (ADC and monoclonal antibody) combined with immunotherapy.[59]

If the promising results in the HER2-low population are confirmed in the ongoing Phase 3 portion of the study, disitamab vedotin could fundamentally redefine the "HER2-targetable" landscape in gastric cancer. It would expand treatment options to a much larger group of patients who currently have no targeted therapies available, potentially doubling or tripling the addressable market for HER2-directed agents in this malignancy.

Table 4: Summary of Efficacy Results from Key Clinical Trials in Gastric/GEJ Cancer

Trial ID	Treatment Regimen	HER2 Status	N	Objective Response Rate (ORR)	Median Progression-Free Survival (PFS)	Median Overall Survival (OS)
RC48-C008 16	Disitamab Vedotin (Monotherapy)	Overexpressing	127	18.1%	3.8 months	7.6 months
NCT05980481 (Phase 2) 60	DV + Toripalimab + Trastuzumab	Overexpressing	51	82.4%	NR	NR
NCT05980481 (Phase 2) 60	DV + Toripalimab + CAPOX	Median/Low	48	72.0%	9.9 months	NR
DV = Disitamab Vedotin; NR = Not Reached

---

V. Clinical Development and Efficacy in Breast Cancer

Disitamab vedotin is being actively developed in breast cancer, demonstrating promising activity in both HER2-positive and the increasingly important HER2-low populations, and showing potential to overcome resistance to existing therapies.

Efficacy in HER2-Positive Advanced Breast Cancer

The pivotal RC48-C006 trial (NCT03500380) was a Phase III study that evaluated disitamab vedotin versus the standard-of-care combination of lapatinib (a TKI) and capecitabine (a chemotherapy agent) in patients with HER2-positive advanced breast cancer with liver metastasis who had been previously treated with trastuzumab and taxanes.[20] The study met its primary endpoint, demonstrating a significant improvement in progression-free survival. Key results included [62]:

• Median PFS: 9.9 months for the disitamab vedotin arm versus 4.9 months for the lapatinib plus capecitabine arm (HR=0.561, P=0.0143).
• Overall Survival: While the OS data were immature at the time of analysis, they showed a favorable trend for the disitamab vedotin arm (median OS not reached vs. 25.9 months; HR=0.56).

Based on these robust results, disitamab vedotin was approved by the NMPA in China in May 2025 for this indication, providing a new, effective treatment option for this patient population.[62]

The Emerging Role in HER2-Low Breast Cancer

One of the most significant areas of development for disitamab vedotin is in HER2-low breast cancer, defined as tumors with an IHC score of 1+ or 2+ without gene amplification by in situ hybridization (ISH).[12] This patient subgroup represents a large unmet need, as they are not eligible for traditional HER2-targeted therapies.

Initial evidence of activity came from a pooled analysis of the Phase I/Ib C001/C003 CANCER studies (NCT02881138, NCT03052634). In a cohort of 66 heavily pretreated patients with HER2-low advanced breast cancer, disitamab vedotin monotherapy at the recommended phase 2 dose (2.0 mg/kg) achieved [12]:

• A confirmed ORR of 33.3% (95% CI: 22.2%–46.0%).
• A median PFS of 5.1 months (95% CI: 4.1–6.6).

A separate single-arm Phase II study reported similar findings in a HER2-low cohort (n=38), with an ORR of 29.0% and a median PFS of 3.6 months.[24] While cross-trial comparisons should be made with caution, these response rates are notable in a patient population typically treated with standard chemotherapy. An exploratory study in the neoadjuvant setting suggested potentially greater activity in patients with IHC 2+/ISH- tumors (42.9% pCR) compared to IHC 1+ tumors (11.1% pCR), indicating a possible relationship between the level of HER2 expression and response, even within the "low" category.[68]

To definitively establish its role in this setting, the Rosy Trial (NCT05904964), a randomized, Phase III study, is currently underway to evaluate disitamab vedotin in patients with hormone receptor-positive, HER2-low metastatic breast cancer who have experienced endocrine resistance.[69]

Table 5: Summary of Efficacy Results from Key Clinical Trials in Breast Cancer

Trial ID	Treatment Regimen	HER2 Status	N	Objective Response Rate (ORR)	Median Progression-Free Survival (PFS)
RC48-C006 63	Disitamab Vedotin	HER2-Positive (with Liver Mets)	N/A	-	9.9 months
C001/C003 (Pooled) 65	Disitamab Vedotin (Monotherapy)	HER2-Low	66	33.3%	5.1 months
Phase 2 (Qu et al.) 24	Disitamab Vedotin (Mono/Combo)	HER2-Low	38	29.0%	3.6 months
Phase 2 (Wu et al.) 70	Disitamab Vedotin (Monotherapy)	HER2-Low (with PAM pathway abnormality)	36	34.3%	3.4 months

A critical question for any new HER2-targeted agent is its activity in patients who have progressed on existing therapies, particularly the current standard of care, T-DXd (Enhertu). Preclinical data has provided a strong rationale for sequencing disitamab vedotin after T-DXd. A study using breast and gastric cancer xenograft models demonstrated that disitamab vedotin was effective at inhibiting tumor growth in models that had developed resistance to and progressed on T-DXd.[18] This finding is mechanistically sound, as the two ADCs have distinct molecular designs: disitamab vedotin utilizes a novel antibody (hertuzumab) and an MMAE payload, whereas T-DXd uses trastuzumab and a topoisomerase I inhibitor payload. This lack of cross-resistance suggests that resistance to one agent may not confer resistance to the other. Clinical case reports have provided anecdotal support for this, showing responses to a disitamab vedotin regimen after failure of other ADCs, and vice versa.[71] This evidence strongly positions disitamab vedotin as a rational therapeutic option for patients with HER2-positive or HER2-low breast cancer following progression on T-DXd, addressing a significant and growing unmet clinical need.

---

VI. Comprehensive Safety and Tolerability Profile

The overall safety and tolerability of a therapeutic agent are as crucial as its efficacy in determining its clinical utility and market acceptance. Across its extensive clinical development program, disitamab vedotin has demonstrated a consistent and manageable safety profile.

Analysis of Common and Grade ≥3 Treatment-Related Adverse Events (TRAEs)

A synthesis of safety data from multiple clinical trials in urothelial, gastric, and breast cancer reveals a predictable pattern of treatment-related adverse events (TRAEs). The most frequently reported TRAEs of any grade are [24]:

• Peripheral Sensory Neuropathy: Often reported as hypoaesthesia or neurotoxicity.
• Hematologic Toxicities: Including leukopenia (decreased white blood cells) and neutropenia (decreased neutrophils).
• Hepatotoxicity: Manifesting as increased liver enzymes (aspartate aminotransferase and alanine aminotransferase).
• Constitutional Symptoms: Such as fatigue (asthenia) and decreased appetite.
• Dermatologic Effects: Primarily alopecia (hair loss).

When focusing on more severe toxicities, the most common Grade ≥3 TRAEs are consistently peripheral sensory neuropathy (reported in up to 18.7% of patients in some studies) and neutropenia (up to 12.1%).[36] These adverse events are known class effects associated with the MMAE payload and are generally manageable with supportive care, dose interruptions, or dose reductions as per study protocols.[41]

Table 6: Summary of Common (≥15%) and Grade ≥3 Treatment-Related Adverse Events (TRAEs) from Combined UC Trials (RC48-C005/C009)

Adverse Event	Any Grade (%)	Grade ≥3 (%)
Peripheral Sensory Neuropathy	68.2%	18.7%
Leukopenia	50.5%	N/A
Aspartate Aminotransferase (AST) Increased	42.1%	N/A
Neutropenia	42.1%	12.1%
Alopecia	40.2%	N/A
Asthenia (Fatigue)	39.3%	N/A
Alanine Aminotransferase (ALT) Increased	35.5%	N/A
Decreased Appetite	31.8%	N/A
Data sourced from combined analysis of 107 patients 36

Comparative Risk Assessment: The Low Incidence of Interstitial Lung Disease (ILD)

One of the most significant aspects of disitamab vedotin's safety profile is its apparent low risk of inducing interstitial lung disease (ILD) or pneumonitis. This stands in stark contrast to its primary competitor, trastuzumab deruxtecan (Enhertu), for which ILD is a major toxicity of concern, carrying a black box warning from the FDA. Clinical studies with Enhertu have reported ILD/pneumonitis rates in the range of 10-14%, with some cases being fatal.[74]

Conversely, the data for disitamab vedotin are highly encouraging in this regard. One Phase 2 study in breast cancer explicitly noted that no drug-related pulmonary toxicity was observed.[22] Another study combining disitamab vedotin with pembrolizumab in urothelial cancer reported that

no patients experienced pneumonitis or ILD.[78] While cross-trial comparisons must be interpreted with caution, this consistent signal of a lower ILD risk is a critical point of differentiation.

This difference in pulmonary toxicity is likely attributable to the distinct cytotoxic payloads. The topoisomerase I inhibitor payload in Enhertu (deruxtecan) is mechanistically implicated in its association with ILD. The MMAE payload in disitamab vedotin has a different toxicity profile, with neuropathy and myelosuppression being more prominent. For clinicians weighing treatment options for patients, particularly those with pre-existing pulmonary conditions or other risk factors for ILD, a significantly better safety profile on such a serious adverse event could be a decisive factor. Should this favorable ILD profile be maintained throughout the ongoing global Phase III trials, it will undoubtedly become a cornerstone of disitamab vedotin's clinical and commercial positioning, presenting it as a potentially safer, yet highly effective, alternative in the HER2-targeted ADC space.

---

VII. Strategic and Commercial Landscape

The journey of disitamab vedotin from a promising asset in China to a global priority for one of the world's largest pharmaceutical companies is a case study in modern biopharmaceutical strategy. The series of high-value transactions involving RemeGen, Seagen, and Pfizer underscores the drug's perceived value and strategic importance.

The RemeGen-Seagen Licensing Agreement: A Landmark Cross-Border Partnership

In a pivotal move in August 2021, Seagen, a recognized global leader in ADC technology, entered into an exclusive worldwide licensing agreement with RemeGen to develop and commercialize disitamab vedotin.[15] The agreement granted Seagen rights to the drug in all territories outside of Asia (excluding Japan and Singapore), where RemeGen retained rights.[14]

The financial terms of the deal were substantial and highlighted the high value placed on the asset. Seagen made an upfront payment of $200 million and agreed to potential future development, regulatory, and commercialization milestone payments of up to $2.4 billion, in addition to tiered royalties on net sales.[15] This agreement was not merely a financial transaction; it was a strategic validation of RemeGen's research and development capabilities by a Western leader in the ADC field. Seagen's CEO, Clay Siegall, noted that the collaboration would leverage Seagen's expertise to "maximize the potential of disitamab vedotin".[15]

The Pfizer Acquisition of Seagen: Strategic Rationale and Implications

The story of disitamab vedotin took another significant turn with Pfizer's acquisition of Seagen. Announced in March 2023 and completed in December 2023, the deal was valued at a total enterprise value of approximately $43 billion.[4] This was one of the largest biopharma acquisitions in recent years and was driven primarily by Pfizer's strategic imperative to bolster its oncology pipeline.[4]

Seagen's world-leading ADC technology and its portfolio of approved and pipeline assets were the central prize of the acquisition. Pfizer explicitly identified Seagen's portfolio, including disitamab vedotin, as a key growth driver, projecting that it could contribute more than $10 billion in risk-adjusted revenues by 2030.[4] Following the acquisition, Pfizer restructured its organization to create a dedicated Pfizer Oncology Division, signaling its commitment to integrating and accelerating the development of its newly acquired assets with its own global scale and resources.[5]

This sequence of events—from RemeGen's innovative in-house development to Seagen's strategic in-licensing and Pfizer's blockbuster acquisition—illustrates a powerful new trend in global drug development. It showcases a shift from a model where Western pharmaceutical companies primarily outsourced manufacturing or early discovery to China, to one where they actively seek out and acquire late-stage, de-risked, and highly innovative assets from Chinese biotechs. This demonstrates the maturation of China's biopharmaceutical ecosystem and its capacity to produce globally competitive therapies that can become strategic pillars for Big Pharma.

Regulatory Trajectory: NMPA Approvals and FDA Designations

Disitamab vedotin's clinical success has been matched by a series of significant regulatory milestones:

• China (NMPA): It has received conditional approvals for three separate indications:
• Locally advanced or metastatic gastric cancer in patients who have received at least two prior systemic therapies.[16]
• Locally advanced or metastatic urothelial carcinoma in patients with HER2 overexpression who have failed platinum-based chemotherapy.[39]
• HER2-positive advanced breast cancer with liver metastasis in patients previously treated with trastuzumab and taxanes.[62]
• United States (FDA): It has received Breakthrough Therapy Designation for the second-line treatment of patients with HER2-expressing, locally advanced or metastatic urothelial cancer who have previously received platinum-containing chemotherapy.[8] This designation is intended to expedite the development and review of drugs for serious conditions where preliminary clinical evidence indicates substantial improvement over available therapy.

---

VIII. Competitive Positioning and Future Outlook

Disitamab vedotin is entering a dynamic and competitive therapeutic landscape, particularly in the HER2-targeted space. Its clinical profile and molecular characteristics position it uniquely against the current standard of care and other emerging therapies.

Comparative Analysis: Disitamab Vedotin vs. Trastuzumab Deruxtecan (Enhertu)

The most critical competitor for disitamab vedotin is trastuzumab deruxtecan (T-DXd, Enhertu), which has established itself as a highly effective ADC in breast, gastric, and other HER2-expressing cancers. The differentiation between these two agents is crucial for understanding their potential roles in clinical practice.

Table 2: Comparison of Key Molecular and Clinical Attributes: Disitamab Vedotin vs. Trastuzumab Deruxtecan (Enhertu)

Attribute	Disitamab Vedotin	Trastuzumab Deruxtecan (Enhertu)
Antibody Target	Novel anti-HER2 mAb (Hertuzumab)	Trastuzumab
Binding Epitope	Distinct epitope on Subdomain IV	Standard trastuzumab epitope on Subdomain IV
Cytotoxic Payload	Monomethyl Auristatin E (MMAE) (Microtubule Inhibitor)	Deruxtecan (DXd) (Topoisomerase I Inhibitor)
Linker Type	Protease-cleavable (vc-linker)	Protease-cleavable (peptide-based)
Drug-to-Antibody Ratio (DAR)	~4	~8
Key Safety Concern	Peripheral Neuropathy, Myelosuppression	Interstitial Lung Disease (ILD)/Pneumonitis
Sources: 8

The key differentiators are the novel antibody, the distinct payload class, the lower DAR, and the divergent safety profiles. The different payloads are particularly important, as they provide a strong mechanistic rationale for a lack of complete cross-resistance between the two drugs.

Therapeutic Sequencing and Overcoming Resistance

The future of HER2-targeted therapy will increasingly rely on the strategic sequencing of agents to manage acquired resistance. Disitamab vedotin is exceptionally well-positioned for this role. Preclinical studies have shown that it retains activity in cancer models that have become resistant to T-DXd.[18] This is a direct result of its different antibody and payload. A tumor that develops resistance to a topoisomerase I inhibitor like deruxtecan may remain sensitive to a microtubule inhibitor like MMAE, and vice versa.

Therefore, a likely clinical paradigm will involve using one agent until progression, followed by the other. Disitamab vedotin could become the standard of care after failure of T-DXd, or in certain patient populations, it could be used first, particularly if its favorable ILD safety profile is a primary consideration for the clinician.

The Landscape of Emerging HER2-Targeted ADCs

The field of HER2-targeted ADCs is not static. Several other agents are in late-stage development and could emerge as future competitors. These include:

• ARX788: A next-generation ADC that has shown a significant PFS benefit in HER2-positive metastatic breast cancer and has also demonstrated activity in HER2-low disease. It carries a risk of ILD, similar to Enhertu.[87]
• SHR-A1811: A third-generation HER2-directed ADC that has shown high rates of pathological complete response as a neoadjuvant monotherapy in early-stage HER2-positive breast cancer.[88]
• TQB2102: A novel bispecific ADC that has produced responses in pretreated, recurrent, or metastatic HER2-positive breast cancer.[87]

The continued emergence of these and other ADCs underscores the rapid innovation in the field and the need for therapies like disitamab vedotin to clearly define their value proposition based on efficacy, safety, and ability to treat resistant or niche patient populations.[2]

---

IX. Conclusion and Strategic Recommendations

Disitamab vedotin has firmly established itself as a highly promising and differentiated HER2-targeted antibody-drug conjugate. Its unique molecular design, featuring a novel high-affinity antibody and a potent MMAE payload with a strong bystander effect, provides a clear mechanistic rationale for its impressive clinical activity. The drug has demonstrated robust and clinically meaningful efficacy in three major tumor types—urothelial carcinoma, gastric cancer, and breast cancer—and has shown unprecedented potential to expand treatment to the large, underserved HER2-low patient population.

The combination of disitamab vedotin with PD-1 inhibitors, particularly in urothelial and gastric cancers, appears to be synergistic and has the potential to displace chemotherapy as a first-line standard of care. Furthermore, its efficacy in preclinical models resistant to trastuzumab deruxtecan (Enhertu) and its favorable safety profile, especially the low incidence of interstitial lung disease, represent major competitive advantages that could drive physician adoption and define its role in therapeutic sequencing.

The strategic acquisition by Pfizer provides the global resources and commercial expertise necessary to maximize the potential of this asset. Based on the comprehensive analysis of its molecular, clinical, and commercial profile, the following strategic directions are recommended:

• Prioritize Global Development in Urothelial Carcinoma: Expedite the completion of ongoing Phase III trials in first-line urothelial carcinoma to establish the disitamab vedotin-immunotherapy combination as the global standard of care.
• Accelerate Development in HER2-Low Cancers: Aggressively pursue the HER2-low indications in both gastric and breast cancer. Success in these large, untapped markets represents the greatest opportunity for market expansion and would solidify disitamab vedotin as a paradigm-shifting therapy.
• Emphasize Differentiated Safety Profile: Prominently feature the low risk of ILD in all clinical communications and marketing efforts. This key safety advantage is a powerful differentiator from Enhertu and can be a primary driver of physician choice, especially for patients with pulmonary comorbidities.
• Investigate Biomarkers for Sequencing: Initiate translational research to identify biomarkers that could predict response or resistance to MMAE-based versus topoisomerase-based ADCs. Such data would provide clinicians with an evidence-based rationale for optimal therapeutic sequencing, further cementing the drug's place in the treatment algorithm.

In conclusion, disitamab vedotin is not merely another HER2-targeted ADC; it is a strategically designed therapeutic with the potential to overcome key mechanisms of resistance, expand treatment to new patient populations, and offer a safer alternative to a major competitor. With focused execution of its late-stage clinical and regulatory strategy, disitamab vedotin is poised to become a cornerstone of HER2-targeted cancer therapy worldwide.

Works cited

1. A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy - PubMed Central, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10544916/
2. Recent ADC Approvals and Their Impact on the Breast Cancer Space, accessed July 3, 2025, https://www.cancernetwork.com/view/recent-adc-approvals-and-their-impact-on-the-breast-cancer-space
3. Mechanisms of Resistance to Antibody–Drug Conjugates - PMC, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9954407/
4. Pfizer Invests $43 Billion to Battle Cancer, accessed July 3, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer-invests-43-billion-battle-cancer
5. Pfizer Completes Acquisition of Seagen, accessed July 3, 2025, https://www.pfizer.com/news/press-release/press-release-detail/pfizer-completes-acquisition-seagen
6. Novel development strategies and challenges for anti-Her2 antibody-drug conjugates - Oxford Academic, accessed July 3, 2025, https://academic.oup.com/abt/article/5/1/18/6515797
7. Disitamab vedotin: a novel antibody-drug conjugates for cancer therapy - PubMed, accessed July 3, 2025, https://pubmed.ncbi.nlm.nih.gov/35506447/
8. Disitamab vedotin: a novel antibody-drug conjugates for cancer therapy - PMC, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9090390/
9. Definition of disitamab vedotin - NCI Drug Dictionary, accessed July 3, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/disitamab-vedotin
10. Disitamab vedotin (PF-08046051) | Pfizer Oncology Development Website, accessed July 3, 2025, https://www.pfizeroncologydevelopment.com/molecule/disitamab-vedotin-
11. Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9636477/
12. Disitamab vedotin, a HER2‐directed antibody‐drug conjugate, in patients with HER2‐overexpression and HER2‐low advanced breast cancer: a phase I/Ib study - PubMed Central, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11260767/
13. What is Disitamab Vedotin used for? - Patsnap Synapse, accessed July 3, 2025, https://synapse.patsnap.com/article/what-is-disitamab-vedotin-used-for
14. Seagen Strikes $2.6 Billion ADC Deal with China's RemeGen - BioSpace, accessed July 3, 2025, https://www.biospace.com/seagen-strikes-2-6-billion-adc-deal-with-china-s-remegen
15. Seagen and RemeGen Announce Exclusive Worldwide License and Co-Development Agreement for Disitamab Vedotin | Nasdaq, accessed July 3, 2025, https://www.nasdaq.com/press-release/seagen-and-remegen-announce-exclusive-worldwide-license-and-co-development-agreement
16. Chinese Regulator Conditionally Approves Disitamab Vedotin in ..., accessed July 3, 2025, https://www.adcreview.com/clinical-trials-update/chinese-regulator-conditionally-approves-disitamab-vedotin-in-advanced-or-metastatic-gastric-cancer/
17. Seagen and RemeGen Announce Exclusive Worldwide License and Co-Development Agreement for Disitamab Vedotin - Business Wire, accessed July 3, 2025, https://www.businesswire.com/news/home/20210809005208/en/Seagen-and-RemeGen-Announce-Exclusive-Worldwide-License-and-Co-Development-Agreement-for-Disitamab-Vedotin
18. Disitamab vedotin in preclinical models of HER2-positive breast and gastric cancers resistant to trastuzumab emtansine and trastuzumab deruxtecan - PubMed, accessed July 3, 2025, https://pubmed.ncbi.nlm.nih.gov/39837059/
19. Enhertu beats Kadcyla in head-to-head breast cancer trial - PPF Group, accessed July 3, 2025, https://www.ppf.eu/en/insights/biotech-market/august-2021-review-of-news-from-the-most-innovative-therapeutic-areas-and-the-bus/enhertu-beats-kadcyla-in-head-to-head-breast-cancer-trial
20. SABCS 2024: Disitamab Vedotin Demonstrates Clinically Meaningful Results in the Treatment of HER2-Positive Advanced Breast Cancer with Liver Metastasis - ADC Review, accessed July 3, 2025, https://www.adcreview.com/clinical-trials-update/phase-3/sabcs-2024-disitamab-vedotin-demonstrates-clinically-meaningful-results-in-the-treatment-of-her2-positive-advanced-breast-cancer-with-liver-metastasis/
21. Abstract 560: Disitamab vedotin, an investigational HER2-directed, accessed July 3, 2025, https://aacrjournals.org/cancerres/article/83/7_Supplement/560/721493/Abstract-560-Disitamab-vedotin-an-investigational
22. Next-Generation HER2-Targeted Antibody–Drug Conjugates in Breast Cancer - MDPI, accessed July 3, 2025, https://www.mdpi.com/2072-6694/16/4/800
23. Summary of Approved HER2 ADCs on The Market & in Clinical Trials | Biopharma PEG, accessed July 3, 2025, https://www.biochempeg.com/article/348.html
24. Disitamab Vedotin Combos Show Efficacy in HER2+ and HER2-Low Breast Cancers, accessed July 3, 2025, https://www.onclive.com/view/disitamab-vedotin-combos-show-efficacy-in-her2-and-her2-low-breast-cancers
25. Next-Generation Anti–HER2-Antibody Drug Conjugates: Extending the Actionability to “HER2-Low” Breast Cancer - ASCO Daily News, accessed July 3, 2025, https://dailynews.ascopubs.org/do/next-generation-anti-her2-antibody-drug-conjugates-extending-actionability-her2-low
26. Use of Antibody–Drug Conjugates in the Early Setting of Breast Cancer - PMC, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11185006/
27. The Bystander Effect of ADCs | Biopharma PEG, accessed July 3, 2025, https://www.biochempeg.com/article/269.html
28. Rational Identification of Novel Antibody‐Drug Conjugate with High Bystander Killing Effect against Heterogeneous Tumors - PMC, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10987111/
29. (PDF) Bystander effect of antibody–drug conjugates: fact or fiction? - ResearchGate, accessed July 3, 2025, https://www.researchgate.net/publication/359343083_Bystander_effect_of_antibody-drug_conjugates_fact_or_fiction
30. A retrospective multicenter study on the efficacy and safety of disitamab vedotin monotherapy versus combination with anti-PD-1 immunotherapy in advanced gastric cancer - ResearchGate, accessed July 3, 2025, https://www.researchgate.net/publication/388111500_A_retrospective_multicenter_study_on_the_efficacy_and_safety_of_disitamab_vedotin_monotherapy_versus_combination_with_anti-PD-1_immunotherapy_in_advanced_gastric_cancer
31. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study - ASCO Publications, accessed July 3, 2025, https://ascopubs.org/doi/10.1200/JCO.19.02318
32. Resistance to Antibody-Drug Conjugates Targeting HER2 in Breast Cancer: Molecular Landscape and Future Challenges - MDPI, accessed July 3, 2025, https://www.mdpi.com/2072-6694/15/4/1130
33. Mechanisms of Resistance to Antibody–Drug Conjugates - ResearchGate, accessed July 3, 2025, https://www.researchgate.net/publication/368590810_Mechanisms_of_Resistance_to_Antibody-Drug_Conjugates
34. Mechanisms of Resistance to Antibody–Drug Conjugates - AACR Journals, accessed July 3, 2025, https://aacrjournals.org/mct/article/15/12/2825/147824/Mechanisms-of-Resistance-to-Antibody-Drug
35. FDA approval makes Enhertu an option for multiple tumour indications - Clinical Trials Arena, accessed July 3, 2025, https://www.clinicaltrialsarena.com/analyst-comment/fda-approval-enhertu-multiple-tumour-indications/
36. ASCO 2022: RC48-ADC For Metastatic Urothelial Carcinoma With HER2-Positive: Combined Analysis of RC48-C005 and RC48-C009 Trials - UroToday, accessed July 3, 2025, https://www.urotoday.com/conference-highlights/asco-2022/asco-2022-bladder-cancer/137628-asco-2022-abstract-4520-rc48-adc-for-metastatic-urothelial-carcinoma-with-her2-positive-combined-analysis-of-rc48-c005-and-rc48-c009-trials.html
37. Disitamab vedotin shows promise in HER2+ metastatic urothelial carcinoma - Urology Times, accessed July 3, 2025, https://www.urologytimes.com/view/disitamab-vedotin-shows-promise-in-her2-metastatic-urothelial-carcinoma
38. Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials - PubMed, accessed July 3, 2025, https://pubmed.ncbi.nlm.nih.gov/37988648/
39. RemeGen Announces Publication of Results from Two Phase II Studies for Disitamab Vedotin in Latest Issue of Journal of Clinical Oncology (JCO) - PR Newswire, accessed July 3, 2025, https://www.prnewswire.com/news-releases/remegen-announces-publication-of-results-from-two-phase-ii-studies-for-disitamab-vedotin-in-latest-issue-of-journal-of-clinical-oncology-jco-301998515.html
40. Disitamab Vedotin in Previously Treated Patients With Advanced HER2-Positive Urothelial Carcinoma - The ASCO Post, accessed July 3, 2025, https://ascopost.com/news/december-2023/disitamab-vedotin-in-previously-treated-patients-with-advanced-her2-positive-urothelial-carcinoma/
41. Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2–Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials - ASCO Publications, accessed July 3, 2025, https://ascopubs.org/doi/10.1200/JCO.22.02912
42. Published in Annals of Oncology: Disitamab Vedotin Combined with PD-1 Inhibitor is a Promising Treatment for Locally Advanced or Metastatic Urothelial Carcinoma - PR Newswire, accessed July 3, 2025, https://www.prnewswire.com/apac/news-releases/published-in-annals-of-oncology-disitamab-vedotin-combined-with-pd-1-inhibitor-is-a-promising-treatment-for-locally-advanced-or-metastatic-urothelial-carcinoma-302345690.html
43. Frontline Disitamab Vedotin Plus Toripalimab Improves PFS and OS in HER2+ Metastatic Urothelial Carcinoma - OncLive, accessed July 3, 2025, https://www.onclive.com/view/frontline-disitamab-vedotin-plus-toripalimab-improves-pfs-and-os-in-her2-metastatic-urothelial-carcinoma
44. Disitamab Vedotin Plus Toripalimab Elicits Responses, Safety in Metastatic Urothelial Carcinoma - OncLive, accessed July 3, 2025, https://www.onclive.com/view/disitamab-vedotin-plus-toripalimab-elicits-responses-safety-in-metastatic-urothelial-carcinoma
45. First-Line Disitamab Vedotin/Toripalimab Shows Benefit in HER2+ la/mUC, accessed July 3, 2025, https://www.targetedonc.com/view/first-line-disitamab-vedotin-toripalimab-shows-benefit-in-her2-la-muc
46. Published in Annals of Oncology: Disitamab Vedotin Combined with PD-1 Inhibitor is a Promising Treatment for Locally Advanced or Metastatic Urothelial Carcinoma - PR Newswire, accessed July 3, 2025, https://www.prnewswire.com/news-releases/published-in-annals-of-oncology-disitamab-vedotin-combined-with-pd-1-inhibitor-is-a-promising-treatment-for-locally-advanced-or-metastatic-urothelial-carcinoma-302345663.html
47. First-Line Disitamab Vedotin Combo Ups Survival in Urothelial Cancer - Oncology Nursing News, accessed July 3, 2025, https://www.oncnursingnews.com/view/first-line-disitamab-vedotin-combo-ups-survival-in-urothelial-cancer
48. Disitamab Vedotin Combo Extends PFS/OS in HER2+ Urothelial Carcinoma, accessed July 3, 2025, https://www.cancernetwork.com/view/disitamab-vedotin-combo-extends-pfs-os-in-her2-urothelial-carcinoma
49. Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab - ASCO Publications, accessed July 3, 2025, https://ascopubs.org/doi/10.1200/JCO.23.01547
50. Balancing effectiveness, toxicity, and individualization: enfortumab vedotin in advanced urothelial cancer - PMC, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11986542/
51. Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab | Journal of Clinical Oncology - ASCO Publications, accessed July 3, 2025, https://ascopubs.org/doi/abs/10.1200/JCO.23.01547?mi=468qtj&af=R&field1=AllField&field2=AllField&sortBy=Ppub&target=default&text1=%22symptom+management%22+OR+%22symptom+Monitoring%22OR+symptom&text2=App+OR+eHealth+OR+digital+OR+Application+OR+Mobile
52. ISRCTN11908197: Disitamab vedotin with pembrolizumab vs chemotherapy in previously untreated urothelial cancer expressing HER2 - ISRCTN Registry, accessed July 3, 2025, https://www.isrctn.com/ISRCTN11908197
53. Phase 3 open-label, randomized, controlled study of disitamab vedotin with pembrolizumab versus chemotherapy in patients with pr - Pfizer Medical Information, accessed July 3, 2025, https://pfizermedical.pfizerpro.com/api/vc/en/medical/assets/512b39a8-c63a-4175-8a12-f8219badc15b/Galsky_P_ASCOGU2024.pdf
54. Evaluating the efficacy and safety of bladder-sparing regimen with Disitamab Vedotin combined with Toripalimab and pelvic lymph node dissection in muscle-invasive bladder cancer patients, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12076858/
55. Antibody-drug Conjugates for HER2-Positive Gastric Cancer | Biopharma PEG, accessed July 3, 2025, https://www.biochempeg.com/article/337.html
56. Disitamab Vedotin (RC48) combined with bevacizumab for treatment of HR-negative/HER2-positive metastatic breast cancer with liver and brain involvement: A case report - PubMed Central, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10498115/
57. Phase II clinical study evaluating the efficacy and safety of disitamab vedotin combined with sintilimab and S-1 in the conversion treatment of HER2-overexpression unresectable gastric cancer. - ASCO Publications, accessed July 3, 2025, https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.TPS428
58. Novel ADC Checkpoint Inhibitor Combo Shows Promise in HER2+ GI Cancers, accessed July 3, 2025, https://www.targetedonc.com/view/novel-adc-checkpoint-inhibitor-combo-shows-promise-in-her2-gi-cancers
59. Frontline Disitamab Vedotin Yields Responses in Gastric/GEJ Cancer With Various HER2 Expression Levels - OncLive, accessed July 3, 2025, https://www.onclive.com/view/frontline-disitamab-vedotin-yields-responses-in-gastric-gej-cancer-with-various-her2-expression-levels
60. Disitamab Vedotin/Toripalimab/Trastuzumab Yield Responses in G/GEJ Cancer, accessed July 3, 2025, https://www.cancernetwork.com/view/disitamab-vedotin-toripalimab-trastuzumab-yield-responses-in-g-gej-cancer
61. 2025 ASCO ｜Oral Presentation: Disitamab Vedotin Achieves Stellar Efficacy as First-Line Therapy for HER2-Expressing Locally Advanced or Metastatic Gastric Cancer - PR Newswire, accessed July 3, 2025, https://www.prnewswire.com/news-releases/2025-asco-oral-presentation-disitamab-vedotin-achieves-stellar-efficacy-as-first-line-therapy-for-her2-expressing-locally-advanced-or-metastatic-gastric-cancer-302470866.html
62. Disitamab Vedotin Gains Approval in China for its Third Indication - ADC Review, accessed July 3, 2025, https://www.adcreview.com/clinical-trials-update/disitamab-vedotin-gains-approval-in-china-for-its-third-indication/
63. RemeGen's Disitamab Vedotin Gains Approval in China for its Third Indication Making it the First ADC Approved for HER2-Positive Advanced Breast Cancer with Liver Metastasis Globally, accessed July 3, 2025, https://www.remegen.com/index.php?v=show&cid=115&id=2584
64. Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes - MDPI, accessed July 3, 2025, https://www.mdpi.com/1422-0067/24/16/12795
65. Disitamab vedotin, a HER2-directed antibody-drug conjugate, in ..., accessed July 3, 2025, https://pubmed.ncbi.nlm.nih.gov/38940019/
66. (PDF) Disitamab Vedotin, a HER2-directed Antibody Drug-Conjugate, in Patients with HER2- positive and HER2-low Advanced Breast Cancer：A Phase 1/1b Study - ResearchGate, accessed July 3, 2025, https://www.researchgate.net/publication/373691479_Disitamab_Vedotin_a_HER2-directed_Antibody_Drug-Conjugate_in_Patients_with_HER2-_positive_and_HER2-low_Advanced_Breast_CancerA_Phase_11b_Study
67. Disitamab Vedotin Combos Are Effective in HER2+, HER2-Low Breast Cancers - Oncology Nursing News, accessed July 3, 2025, https://www.oncnursingnews.com/view/disitamab-vedotin-combos-are-effective-in-her2-her2-low-breast-cancers
68. An exploratory clinical study investigating the neoadjuvant treatment of HER2-low expressing, stage II-III breast cancer with disitamab vedotin combined with penpulimab (RCVDBCIIR005). - ASCO Publications, accessed July 3, 2025, https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e12620
69. Disitamab Vedotin RC48 in Hormone Receptor Positive HER2low Metastatic Breast Cancer the Rosy Trial (NCT05904964) - CareAcross, accessed July 3, 2025, https://www.careacross.com/clinical-trials/trial/NCT05904964
70. Disitamab Vedotin Shows Early Efficacy in HER2-Expressing Breast Cancer With PAM Pathway Abnormalities - OncLive, accessed July 3, 2025, https://www.onclive.com/view/disitamab-vedotin-shows-early-efficacy-in-her2-expressing-breast-cancer-with-pam-pathway-abnormalities
71. Combination therapy with antibody‑drug conjugate RC48 (disitamab vedotin) and zimberelimab (PD‑1 inhibitor) successfully controlled recurrent HER2‑positive breast cancer resistant to trastuzumab emtansine: A case report, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10398622/
72. Partial response to trastuzumab deruxtecan (DS8201) following progression in HER2-amplified breast cancer with pulmonary metastases managed with disitamab vedotin (RC48): a comprehensive case report and literature review, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11215061/
73. Retrospective analysis of the efficacy and safety of disitamab vedotin (RC48) in Chinese patients with HER2-positive or HER2-low metastatic breast cancer. - ASCO, accessed July 3, 2025, https://www.asco.org/abstracts-presentations/ABSTRACT483906
74. ENHERTU® Reduced the Risk of Death by 30% Versus Ramucirumab Plus Paclitaxel as a Second-Line Therapy in Patients with HER2 Positive Unresectable or Metastatic Gastric Cancer in DESTINY-Gastric04 Phase 3 Trial - BioSpace, accessed July 3, 2025, https://www.biospace.com/press-releases/enhertu-reduced-the-risk-of-death-by-30-versus-ramucirumab-plus-paclitaxel-as-a-second-line-therapy-in-patients-with-her2-positive-unresectable-or-metastatic-gastric-cancer-in-destiny-gastric04-phase-3-trial
75. Interstitial Lung Disease/Pneumonitis | ENHERTU® (fam-trastuzumab deruxtecan-nxki), accessed July 3, 2025, https://www.enhertuhcp.com/en/managing-adverse-reactions/interstitial-lung-disease-pneumonitis
76. Incidence and Outcomes of Pneumonitis/Interstitial Lung Disease in Patients Receiving Trastuzumab Deruxtecan - Journal of Hematology Oncology Pharmacy, accessed July 3, 2025, https://jhoponline.com/issue-archive/2024-issues/march-2024-vol-14-special-feature/incidence-and-outcomes-of-pneumonitis-interstitial-lung-disease-in-patients-receiving-trastuzumab-deruxtecan
77. Incidence of interstitial lung disease and cardiotoxicity with trastuzumab deruxtecan in breast cancer patients: a systematic review and single-arm meta-analysis - PubMed Central, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10485391/
78. Disitamab vedotin/pembrolizumab shows promise in HER2-expressing urothelial carcinoma, accessed July 3, 2025, https://www.urologytimes.com/view/disitamab-vedotin-pembrolizumab-shows-promise-in-her2-expressing-urothelial-carcinoma
79. EX-2.1 - SEC.gov, accessed July 3, 2025, https://www.sec.gov/Archives/edgar/data/1060736/000119312521278354/d196037dex21.htm
80. O'Melveny Represents RemeGen in its Exclusive Worldwide License Agreement with Seagen Inc., accessed July 3, 2025, https://www.omm.com/news/press-releases/o-melveny-represents-remegen-in-its-exclusive-worldwide-license-agreement-with-seagen-inc/
81. Seagen Secures $2.6B Deal with RemeGen for Novel HER2-Targeting Cancer Drug, accessed July 3, 2025, https://trial.medpath.com/news/c3f15855b1709130/seagen-secures-2-6b-deal-with-remegen-for-novel-her2-targeting-cancer-drug
82. Biopharma Breakthrough: Examining Pfizer´s Strategic Seagen Acquisition, accessed July 3, 2025, https://www.sgfer.org/wp-content/uploads/2024/01/Pfizer-Seagen.pdf
83. With $43B buyout, Pfizer sees cancer specialist Seagen as a 'goose' laying 'golden eggs' - Fierce Pharma, accessed July 3, 2025, https://www.fiercepharma.com/pharma/43b-buyout-pfizer-sees-seagen-its-golden-goose
84. Pfizer Clears Final Regulatory Hurdles to Acquire Seagen Inc. - Pharmaceutical Executive, accessed July 3, 2025, https://www.pharmexec.com/view/pfizer-clears-final-regulatory-hurdles-to-acquire-seagen-inc
85. Pfizer wins regulatory approval for its $43B acquisition of Seattle-area biotech giant Seagen, accessed July 3, 2025, https://www.geekwire.com/2023/pfizer-wins-regulatory-approval-for-its-43b-acquisition-of-seattle-area-biotech-giant-seagen/
86. Trastuzumab deruxtecan (DS-8201) | HER2 ADC - MedchemExpress.com, accessed July 3, 2025, https://www.medchemexpress.com/trastuzumab-deruxtecan-1.html
87. New ADCs Aim to Strengthen the HER2+ Breast Cancer Paradigm ..., accessed July 3, 2025, https://www.onclive.com/view/new-adcs-aim-to-strengthen-the-her2-breast-cancer-paradigm-and-join-t-dxd-and-t-dm1
88. Third-Generation HER2-Directed ADC in Breast Cancer Posts Positive Data, accessed July 3, 2025, https://www.oncologynewscentral.com/breast-cancer/third-generation-her2-directed-adc-in-breast-cancer-posts-positive-data
89. Next-Generation HER2-Targeted Antibody–Drug Conjugates in Breast Cancer - PMC, accessed July 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10887217/
90. Clinical Developments of Antibody-Drug Conjugates (ADCs) in HR+/HER2– mBC - OncLive, accessed July 3, 2025, https://www.onclive.com/view/clinical-developments-of-antibody-drug-conjugates-adcs-in-hr-her2-mbc