Comprehensive Report on QLS-31905: A Novel CLDN18.2/CD3 Bispecific T-Cell Engager for Advanced Solid Tumors

Executive Summary

QLS-31905 is an investigational bispecific T-cell engager (BiTE) antibody developed by Qilu Pharmaceutical Co., Ltd., engineered to target two distinct proteins: Claudin 18.2 (CLDN18.2), a tumor-associated antigen, and CD3, a component of the T-cell receptor complex.[1] This dual-targeting mechanism is designed to physically link a patient's own cytotoxic T-cells to cancer cells expressing CLDN18.2, thereby inducing potent, targeted tumor cell lysis. The development of QLS-31905 is strategically positioned within a therapeutic landscape recently validated by the regulatory approval of zolbetuximab (Vyloy), the first-in-class monoclonal antibody targeting CLDN18.2.

The clinical development program for QLS-31905 is spearheaded by the Phase 1 monotherapy trial, NCT05278832, which has provided crucial proof-of-concept data in a heavily pre-treated population of patients with advanced solid tumors. Updated results presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated encouraging anti-tumor activity. Among 33 evaluable CLDN18.2-positive patients, the objective response rate (ORR) was 18.2%, and the disease control rate (DCR) was a notable 87.9%. Efficacy was particularly pronounced in patients with pancreatic adenocarcinoma, who achieved an ORR of 25.0%.[3] These results are complemented by a manageable safety profile. A key concern for T-cell engaging therapies, Cytokine Release Syndrome (CRS), occurred in 21.5% of patients, but severe (Grade

≥3) events were infrequent (3.8%), and all cases were reversible. Critically, a maximum tolerated dose (MTD) was not reached, suggesting a favorable therapeutic window.[3]

Building on these findings, Qilu Pharmaceutical has advanced QLS-31905 into a Phase 1b/2 combination therapy trial, NCT06041035. This study is designed to evaluate QLS-31905 alongside standard-of-care chemotherapy regimens as a first-line treatment for CLDN18.2-positive gastric/gastroesophageal junction (G/GEJ) cancer, pancreatic cancer, and other solid tumors.[5] This strategic pivot from the refractory to the front-line setting reflects an aggressive and pragmatic development pathway aimed at integrating QLS-31905 into current clinical practice.

The therapeutic landscape for CLDN18.2-positive cancers is intensely competitive. The approval of zolbetuximab has established a clinical benchmark, while a formidable pipeline of next-generation modalities, particularly antibody-drug conjugates (ADCs) from major pharmaceutical companies, is rapidly advancing. QLS-31905's potential for differentiation lies in its potent T-cell redirecting mechanism, its promising efficacy signal in pancreatic cancer—an area of profound unmet need—and a safety profile that appears manageable. The forthcoming data from the combination therapy studies will be paramount in defining its ultimate role and commercial viability in this dynamic and high-value oncology market.

The Therapeutic Rationale: Targeting Claudin 18.2 in Oncology

Biology and Pathophysiology of CLDN18.2

Claudin 18.2 (CLDN18.2) is a 27-kilodalton quadruple transmembrane protein that serves as a critical structural component of tight junctions in epithelial cells.[2] It is the A2 isoform of the claudin-18 protein, a member of a larger family of proteins responsible for regulating the permeability of the paracellular space, thereby maintaining the barrier function and polarity of epithelial layers.[1]

The therapeutic attractiveness of CLDN18.2 stems from its highly restricted expression profile in healthy tissues. Under normal physiological conditions, CLDN18.2 expression is strictly confined to the short-lived, differentiated epithelial cells of the gastric mucosa.[1] Within these cells, the protein is localized to the apical side and is sequestered within the tight junction complexes between adjacent cells. This anatomical sequestration effectively "buries" the extracellular loops of the protein, rendering them inaccessible to circulating therapeutic antibodies administered intravenously.[6]

The central premise for targeting CLDN18.2 in oncology arises from a fundamental change that occurs during malignant transformation. As gastric cells become cancerous, the highly organized cellular architecture is disrupted, leading to a loss of cell polarity.[6] This disruption causes the tight junctions to break down, resulting in the aberrant exposure of CLDN18.2 epitopes across the entire surface of the tumor cell membrane.[6] This process transforms CLDN18.2 from a hidden structural protein into an exposed, highly specific tumor-associated antigen (TAA) that is readily accessible to therapeutic agents in the bloodstream. This cancer-specific surface presentation, coupled with its near-absence in other healthy tissues, creates an ideal therapeutic window, allowing for targeted destruction of cancer cells while minimizing potential on-target, off-tumor toxicity.[1]

Prevalence and Prognostic Significance

The expression of CLDN18.2 is not limited to gastric cancer. Upon malignant transformation, it is ectopically expressed in a variety of other solid tumors, making it a target of broad interest. Significant expression has been documented in primary and metastatic lesions of gastric and gastroesophageal junction (G/GEJ) adenocarcinoma, pancreatic cancer (PAC), esophageal cancer, biliary tract cancer, non-small-cell lung cancer, and ovarian cancer.[2]

Epidemiological data derived from the large-scale screening programs of the pivotal zolbetuximab clinical trials provide a robust estimate of the addressable patient population. Across both the SPOTLIGHT and GLOW trials, approximately 38% of screened patients with G/GEJ adenocarcinoma were found to have CLDN18.2-positive tumors.[13] For the purposes of these trials, positivity was defined by a stringent cutoff: moderate-to-strong membranous staining in

≥75% of tumor cells as determined by a validated immunohistochemistry (IHC) assay.[10] This specific cutoff is now linked to the approved companion diagnostic for zolbetuximab, the VENTANA CLDN18 (43-14A) RxDx Assay.[16]

The development of other CLDN18.2-targeted agents, however, suggests that this patient population could be expanded. Several clinical trials for investigational therapies, including antibody-drug conjugates (ADCs) and QLS-31905 itself, are utilizing more inclusive expression cutoffs. For instance, the Phase 1 trial of QLS-31905 defined positivity as expression in ≥1% of tumor cells, while trials for ADCs like IBI343 have explored cutoffs such as ≥40% or ≥60%.[3] This exploration of lower expression thresholds could significantly broaden the number of patients eligible for CLDN18.2-targeted therapies in the future. A crucial characteristic of CLDN18.2 as a biomarker is its stability during disease progression; expression is generally maintained between primary tumors and their metastatic sites, allowing for reliable assessment of eligibility from either tissue source.[8]

Validation of CLDN18.2 as a Therapeutic Target: The Zolbetuximab Precedent

The clinical and commercial viability of targeting CLDN18.2 was definitively established with the development and subsequent regulatory approval of zolbetuximab (Vyloy, formerly IMAB362), a first-in-class chimeric IgG1 monoclonal antibody developed by Astellas Pharma.[10] Zolbetuximab functions by binding with high specificity to the exposed extracellular loops of CLDN18.2 on the surface of tumor cells. This binding event initiates two primary immune-mediated cell-killing mechanisms: antibody-dependent cellular cytotoxicity (ADCC), where immune effector cells like natural killer (NK) cells are recruited to lyse the tumor cell, and complement-dependent cytotoxicity (CDC), which involves the activation of the complement cascade to form pores in the tumor cell membrane.[6]

The validation of this approach was achieved in two landmark, global Phase 3 trials: SPOTLIGHT and GLOW. Both studies evaluated zolbetuximab in the first-line setting for patients with locally advanced unresectable or metastatic, HER2-negative, CLDN18.2-positive G/GEJ adenocarcinoma.

• The SPOTLIGHT trial randomized 565 patients to receive either zolbetuximab plus the mFOLFOX6 chemotherapy regimen (oxaliplatin, leucovorin, and fluorouracil) or placebo plus mFOLFOX6. The study met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS), with a median PFS of 10.61 months in the zolbetuximab arm versus 8.67 months in the placebo arm (Hazard Ratio 0.751). It also met the key secondary endpoint of overall survival (OS), with a median OS of 18.23 months versus 15.54 months, respectively (HR 0.750).[13]
• The GLOW trial evaluated zolbetuximab in combination with the CAPOX chemotherapy regimen (capecitabine and oxaliplatin). This study also met its primary endpoint, with a median PFS of 8.21 months for the zolbetuximab combination versus 6.80 months for placebo plus CAPOX (HR 0.687). Median OS was also significantly improved.[17]

Based on these robust results, the U.S. Food and Drug Administration (FDA) approved zolbetuximab on October 18, 2024, for this indication, concurrently approving the companion diagnostic assay.[17] This milestone not only provided a new standard of care but also cemented CLDN18.2 as a clinically validated and actionable biomarker in oncology. The approval of zolbetuximab serves both to de-risk the biological rationale for targeting CLDN18.2 and to establish a formidable clinical and commercial benchmark. This duality creates a complex strategic landscape for emerging agents like QLS-31905. The validation of the target significantly reduces the fundamental biological risk for Qilu Pharmaceutical's development program. However, it also defines the new standard of care for first-line CLDN18.2-positive G/GEJ cancer, against which all subsequent therapies will be measured. Consequently, QLS-31905 cannot succeed merely by demonstrating clinical activity; it must provide a compelling reason for clinicians to choose it over the established zolbetuximab regimen. This could be achieved through superior efficacy (a significantly higher response rate or longer survival), a more favorable safety and tolerability profile (e.g., less nausea and vomiting, which are common with zolbetuximab [27]), enhanced convenience, or potent activity in a distinct patient population where zolbetuximab is not yet approved, such as pancreatic cancer. This competitive context fundamentally reframes the interpretation of QLS-31905's clinical data, which must be viewed not in isolation but in direct comparison to the performance of the market incumbent.

QLS-31905: Molecular Design and Preclinical Profile

Mechanism of Action

QLS-31905 is explicitly defined as a bispecific T-cell engager (BiTE), a sophisticated class of immunotherapy engineered to harness the cytotoxic potential of the patient's own immune system.[1] Unlike conventional monoclonal antibodies that have a single target, QLS-31905 possesses two distinct antigen-binding domains on a single molecular scaffold. One arm of the antibody is designed to bind with high specificity to the CLDN18.2 tumor-associated antigen on the surface of cancer cells. The other arm is engineered to bind to the CD3 epsilon (

CD3ϵ) subunit, a key component of the T-cell receptor (TCR) complex present on the surface of all T-cells.[1]

This dual-binding capability allows QLS-31905 to function as a molecular bridge, physically crosslinking a cytotoxic T-lymphocyte (CTL) with a CLDN18.2-expressing tumor cell. This forced proximity creates an artificial immunological synapse that potently activates the T-cell. A critical feature of this mechanism is that T-cell activation occurs independently of the traditional signaling pathway, which requires T-cell receptor recognition of a specific peptide antigen presented by major histocompatibility complex (MHC) molecules on the cancer cell. By directly engaging the CD3 complex, QLS-31905 bypasses this requirement, enabling polyclonal T-cell activation and redirecting any nearby T-cell to kill the targeted tumor cell. This leads to a cascade of downstream events, including T-cell proliferation, cytokine secretion, and the delivery of cytotoxic granules (perforin and granzymes) into the tumor cell, ultimately inducing apoptosis and cell lysis.[1]

Preclinical Efficacy

The anti-tumor activity of QLS-31905 was rigorously evaluated in a series of preclinical studies, as reported at the American Association for Cancer Research (AACR) Annual Meeting in 2022.[2]

In vitro experiments demonstrated that QLS-31905 exhibited potent cytotoxic activity against multiple CLDN18.2-positive cell lines. This included both engineered cell lines created to express the target (HEK293-hCLDN18.2) and established gastric cancer cell lines that endogenously express the protein (NCI-N87 CLDN18.2). These studies confirmed the molecule's ability to effectively mediate T-cell killing of target cells in a controlled laboratory setting.[2]

The promising in vitro results were subsequently translated into an in vivo setting. In a humanized mouse model bearing NCI-N87 CLDN18.2 tumors—a model in which mice are engrafted with human immune cells to better recapitulate the drug's mechanism of action—QLS-31905 demonstrated superior efficacy in controlling tumor growth. This finding was critical for confirming that the drug could effectively engage T-cells and mediate anti-tumor activity within a complex living biological system, providing a strong rationale for advancing into human clinical trials.[2]

Preclinical Safety and Comparative Analysis

Before human testing, the safety profile of QLS-31905 was assessed in a 4-week repeated-dose toxicology study conducted in cynomolgus monkeys, a standard non-human primate model for antibody therapeutics. The results of this study indicated that QLS-31905 was safe and well-tolerated at doses up to 10 mg/kg, providing an initial safety margin for the design of the first-in-human clinical trial.[2]

A particularly significant finding from the preclinical data package was a direct head-to-head comparison with AMG 910, another anti-CLDN18.2/CD3 bispecific antibody that was in development. While both molecules demonstrated similar efficacy in killing tumor cells, in vitro cytokine release assays revealed a key difference: QLS-31905 induced significantly lower levels of cytokine release compared to AMG 910.[2] This preclinical result suggests a deliberate "bio-better" development strategy by Qilu Pharmaceutical. A fast-follower approach in drug development necessitates a point of superiority over existing or competing molecules. The explicit benchmarking against AMG 910 in the AACR abstract indicates that Qilu's researchers identified excessive cytokine release as a primary clinical liability for this class of drugs. Cytokine release is the direct preclinical correlate of clinical CRS, a potentially severe and dose-limiting toxicity associated with T-cell engaging therapies. By engineering QLS-31905 to have a dampened cytokine induction profile while retaining potent efficacy, Qilu positioned the drug to potentially have a superior safety profile in humans. This foresight likely influenced the design of the Phase 1 trial, including starting dose selection and escalation schemes, with the strategic goal of establishing a wider therapeutic window and a key point of clinical differentiation.

Clinical Evaluation in Monotherapy: The QLS31905-101 (NCT05278832) Study

Study Design and Methodology

The first-in-human evaluation of QLS-31905 was conducted in study QLS31905-101, a multi-center, open-label, Phase 1 clinical trial registered under the identifier NCT05278832.[28] The primary objectives of this study were to assess the safety, tolerability, and pharmacokinetic (PK) profile of QLS-31905 monotherapy and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). A secondary objective was to evaluate preliminary anti-tumor efficacy.[4]

The trial enrolled patients with histologically or cytologically confirmed advanced solid tumors who had experienced disease progression on, were intolerant to, or were otherwise not candidates for available standard therapies.[3] This eligibility criteria defined a heavily pre-treated patient population, which is characteristic of first-in-human oncology trials. Key inclusion criteria included an age of 18 years or older, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function.[28]

The study was structured in two main parts: a dose-escalation phase followed by a dose-expansion phase.[3]

• Dose Escalation: This phase utilized an accelerated titration design for the initial dose levels, followed by a conventional interval 3+3 design. Patients were enrolled into sequential cohorts to receive escalating doses of QLS-31905 administered via intravenous infusion. The dosing schedule explored a wide range, starting at 0.5 µg/kg weekly (QW) and escalating through multiple levels up to 1200 µg/kg bi-weekly (Q2W). A priming dose strategy was introduced at the 350 µg/kg cohort and above to mitigate potential first-dose toxicities.[3] The primary endpoints for this phase were the incidence of dose-limiting toxicities (DLTs) and the determination of the MTD.[4]
• Dose Expansion: Following the identification of safe and biologically active dose levels, the study proceeded to a dose-expansion phase. In this part, cohorts of patients with CLDN18.2-positive tumors (defined as expression in ≥1% of tumor cells by IHC) were enrolled to receive QLS-31905 at selected promising doses. The primary endpoint for the expansion phase was the objective response rate (ORR), with secondary endpoints including disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).[3]

Safety and Tolerability Profile (Integrated Analysis)

The safety and tolerability of QLS-31905 have been reported at two key time points: an initial dataset presented at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress in 2023 (data cutoff July 17, 2023; N=52) and a more mature, larger dataset presented at the ASCO Annual Meeting in 2025 (data cutoff July 26, 2024; N=79).[3]

A critical finding across both analyses was the favorable overall tolerability of the drug. No DLTs were observed during the dose-escalation phase, and consequently, the MTD was not reached, even at the highest dose level of 1200 µg/kg Q2W.[3] This indicates a wide therapeutic window and supports further evaluation of these higher dose levels.

According to the more mature ASCO 2025 data, treatment-related adverse events (TRAEs) of any grade occurred in 100% of the 79 treated patients, which is expected in this patient population. Grade ≥3 TRAEs were reported in 34 patients (43.0%), an increase from the 40.4% rate reported in the smaller ESMO 2023 dataset, likely reflecting a larger patient cohort and longer duration of treatment exposure.[3] The most common Grade

≥3 TRAEs reported in the ASCO 2025 update were hematological in nature, including lymphocyte count decreased (21.5%) and neutrophil count decreased (3.8%), along with γ-glutamyl transferase increased (3.8%), anemia (3.8%), and CRS (3.8%).[3] Treatment was discontinued due to TRAEs in only two patients (2.5%), for abdominal pain and CRS, respectively, and no TRAEs led to death.[3]

Cytokine Release Syndrome (CRS): As a T-cell engaging bispecific antibody, CRS is a key adverse event of special interest. The overall incidence of CRS (any grade) was 21.5% (17 of 79 patients) in the ASCO 2025 dataset.[3] Importantly, the rate of severe CRS was low. The ESMO 2023 report noted two patients with Grade

≥3 CRS, both in the 350 µg/kg QW cohort.[4] The comprehensive ASCO 2025 update confirmed a low incidence of severe events, with two patients experiencing Grade 3 CRS and one patient experiencing Grade 4 CRS, for a total Grade

≥3 rate of 3.8%. All patients who experienced CRS recovered, indicating that the events were manageable with appropriate supportive care.[3] This manageable rate of severe CRS is a clinically meaningful finding that directly corroborates the preclinical hypothesis of a dampened cytokine induction profile. For this class of drugs, CRS management is a significant clinical challenge that can limit dosing, require hospitalization, and restrict use to specialized academic centers. A low rate of severe CRS suggests that QLS-31905 may be safer and easier to administer, potentially allowing for its use in broader clinical settings, thereby establishing a tangible competitive advantage.

Anti-Tumor Activity (Integrated Analysis)

The preliminary efficacy of QLS-31905 monotherapy has shown a maturing and strengthening signal as more patients have been treated and followed for longer durations.

The initial data from ESMO 2023, based on 27 efficacy-evaluable patients, showed an ORR of 11.1% and a DCR of 63.0%. At this early stage, three patients had achieved a partial response (PR), including two with pancreatic cancer and one with gallbladder cancer, all of whom had moderate-to-high CLDN18.2 expression.[4]

The updated analysis from ASCO 2025, focusing on 33 evaluable CLDN18.2-positive patients from the expansion cohorts, demonstrated a more robust efficacy signal in this heavily pre-treated population (61.8% had received ≥2 prior lines of therapy) [3]:

• Overall Efficacy: The confirmed ORR was 18.2% (95% Confidence Interval [CI]: 6.98%, 35.46%), with six patients achieving a PR (three with G/GEJ cancer and three with PAC). The DCR was an impressive 87.9% (95% CI: 71.80%, 96.60%).
• Survival Outcomes: The median PFS for this population was 4.21 months (95% CI: 2.99, 5.55), and the median OS was 9.53 months (95% CI: 7.69, not evaluable).

When analyzed by specific tumor types within the higher-dose cohorts (350–1200 µg/kg Q2W), the data revealed distinct patterns of activity [3]:

• G/GEJ Cancer (N=19): In patients with gastric or gastroesophageal junction cancer, the ORR was 15.8%, with a DCR of 89.5%. The median PFS was 4.40 months, and the median OS was 9.20 months.
• Pancreatic Cancer (PAC) (N=12): In patients with pancreatic adenocarcinoma, QLS-31905 demonstrated even more pronounced activity, with an ORR of 25.0% and a DCR of 91.7%. The median PFS was 3.94 months, and the median OS had not yet been reached at the time of data cutoff.

The efficacy signal in pancreatic cancer is particularly noteworthy and may represent the most promising strategic path forward for QLS-31905. The current standard of care for metastatic pancreatic cancer offers limited efficacy, and it remains an area of profound unmet medical need.[12] Zolbetuximab is still in Phase 2 development for this indication, meaning there is no approved CLDN18.2-targeted therapy.[15] An ORR of 25% in a heavily pre-treated, refractory pancreatic cancer population is a very strong signal of clinical activity. This suggests that QLS-31905 could potentially establish a first-in-class or best-in-class position for CLDN18.2-positive pancreatic cancer, allowing it to build a market foothold in a high-value indication while circumventing a direct initial confrontation with zolbetuximab in the G/GEJ space. The inclusion of a dedicated pancreatic cancer arm in the ongoing combination trial confirms that Qilu is actively pursuing this strategic avenue.[5]

Patient Population	N	ORR (95% CI)	DCR (95% CI)	Median PFS (months, 95% CI)	Median OS (months, 95% CI)	Key Grade ≥3 TRAEs (%)
All CLDN18.2+ Patients	33	18.2% (7.0, 35.5)	87.9% (71.8, 96.6)	4.21 (2.99, 5.55)	9.53 (7.69, NE)	Lymphocyte count dec. (21.5%), CRS (3.8%), Neutrophil count dec. (3.8%)
G/GEJ Cancer Patients	19	15.8%	89.5%	4.40	9.20	Specific rates for subgroup not reported
Pancreatic Cancer Patients	12	25.0%	91.7%	3.94	Not Reached	Specific rates for subgroup not reported
Table 1: Summary of Safety and Efficacy from the Phase 1 Monotherapy Trial (NCT05278832) - ASCO 2025 Data.3 CI = Confidence Interval; NE = Not Evaluable.

Pharmacokinetic (PK) Analysis

Pharmacokinetics, the study of how a drug is absorbed, distributed, metabolized, and excreted (ADME), is a key component of early-phase clinical trials.[31] The protocols for the QLS-31905 trials included the collection of serial serum samples to characterize its PK profile, measuring parameters such as maximum concentration (

Cmax​), time to maximum concentration (Tmax​), and terminal elimination half-life (T1/2​).[5]

The PK analysis from the updated Phase 1 data presented at ASCO 2025 yielded two important findings.[3] First, the exposure to QLS-31905, as measured by serum concentrations, was generally linear with the administered dosage. This means that as the dose was increased, the resulting drug levels in the body increased proportionally, indicating predictable and well-behaved pharmacokinetics. Second, there was no observed tendency for drug accumulation after multiple administrations on either the weekly or bi-weekly schedules. This finding is crucial for safety, as it suggests that the drug is cleared from the body effectively between doses, reducing the risk of toxicity from drug buildup over time and supporting the viability of the tested dosing regimens.[3]

Clinical Strategy in Combination Regimens: The QLS31905-201 (NCT06041035) Study and Beyond

Rationale for Combination Therapy

Following the establishment of monotherapy proof-of-concept, the logical next step in the development of a novel oncology agent is to evaluate its potential in combination with existing standards of care. The scientific rationale for combining a T-cell engager like QLS-31905 with cytotoxic chemotherapy is multifaceted and aims for synergistic anti-tumor effects. Chemotherapy can provide a rapid debulking of the tumor, reducing the overall cancer burden that the immune system must address. Furthermore, chemotherapy-induced cell death can lead to the release of tumor antigens and damage-associated molecular patterns (DAMPs), which can enhance immune recognition. Some chemotherapeutic agents may also favorably modulate the tumor microenvironment by depleting immunosuppressive cells (e.g., regulatory T-cells or myeloid-derived suppressor cells), making it more permissive to the infiltration and function of the T-cells activated by QLS-31905.

Design of the Phase 1b/2 Combination Study (NCT06041035)

Reflecting this strategy, Qilu Pharmaceutical initiated study QLS31905-201 (NCT06041035), a Phase 1b/2 clinical trial designed to assess the efficacy and safety of QLS-31905 administered concurrently with standard-of-care chemotherapy.[5] This study represents a critical strategic advancement, moving QLS-31905 from the heavily pre-treated, refractory setting of the monotherapy trial into the

first-line treatment setting for patients with CLDN18.2-positive advanced solid tumors.[5]

The trial employs an open-label, non-randomized, parallel assignment design to evaluate QLS-31905 with different chemotherapy backbones tailored to specific, high-priority cancer types. The study is divided into two parts: Part A is a dose-finding phase to establish the MTD and RP2D of QLS-31905 when given in combination with chemotherapy, and Part B is an expansion phase to evaluate the efficacy of the combination at the determined RP2D.[5] The study includes three primary experimental arms:

• Arm 1 (Pancreatic Cancer): QLS-31905 is combined with the standard regimen of nab-paclitaxel (125 mg/m² on days 1, 8, and 15) and gemcitabine (1000 mg/m² on days 1, 8, and 15) of each cycle.[5]
• Arm 2 (G/GEJ Cancer): QLS-31905 is combined with the XELOX (or CAPOX) regimen, consisting of oxaliplatin (85 mg/m² on days 1 and 15) and capecitabine (1000 mg/m² orally twice daily on days 1-7 and 15-21) for up to six cycles.[5]
• Arm 3 (Other Solid Tumors): This arm is designed to explore activity in other CLDN18.2-expressing tumors, with a specific focus on biliary tract cancer. Patients in this arm receive QLS-31905 combined with gemcitabine (1000 mg/m² on days 1 and 8) and cisplatin (25 mg/m² on days 1 and 8).[5]

The primary endpoints for the study are MTD and RP2D for Part A, with efficacy measures such as ORR becoming primary in Part B. Key secondary endpoints include DCR, PFS, OS, and a detailed characterization of the pharmacokinetic profile of QLS-31905 in the combination setting.[5] This trial's design reveals a commercially astute and aggressive clinical development plan. By leapfrogging directly to the first-line setting and partnering with globally recognized standard-of-care chemotherapy backbones, Qilu is pursuing a pragmatic and capital-efficient path to market. This strategy aims to integrate QLS-31905 into existing clinical workflows, which, if successful, would facilitate faster physician adoption by adding the drug to familiar regimens. This approach mirrors the successful development strategy employed for zolbetuximab.[25]

Study Arm	Target Indication	Phase Part	QLS-31905 Dosing	Chemotherapy Regimen (Drug, Dose, Schedule)
Arm 1	Pancreatic Cancer	Part A/B	Dose escalation (Part A), RP2D (Part B)	Nab-paclitaxel: 125 mg/m² IV (D1, D8, D15) Gemcitabine: 1000 mg/m² IV (D1, D8, D15)
Arm 2	G/GEJ Cancer	Part B	RP2D from Part A	Oxaliplatin: 85 mg/m² IV (D1, D15) Capecitabine: 1000 mg/m² PO BID (D1-7, D15-21)
Arm 3	Biliary Tract / Other	Part B	RP2D from Part A	Gemcitabine: 1000 mg/m² IV (D1, D8) Cisplatin: 25 mg/m² IV (D1, D8)
Table 2: Design of the Phase 1b/2 Combination Therapy Trial (NCT06041035).5 IV = Intravenous; PO = Oral; BID = Twice Daily; D = Day; RP2D = Recommended Phase 2 Dose.

Future Directions: The NCT06942767 Study

The forward-looking clinical strategy for QLS-31905 is further illuminated by the registration of a future trial, NCT06942767.[33] This planned Phase 2 study will investigate a triplet combination for the first-line treatment of CLDN18.2-positive G/GEJ adenocarcinoma. The regimen will consist of QLS-31905, the XELOX chemotherapy backbone, and QL2107, another investigational agent from Qilu Pharmaceutical's pipeline. This indicates an intent to explore proprietary combinations, potentially creating more durable intellectual property and capturing greater value if the triplet regimen proves superior to the doublet.

Competitive Landscape and Strategic Positioning

The Established Benchmark: Zolbetuximab (Vyloy)

The competitive environment for CLDN18.2-targeted therapies is defined by the presence of a first-to-market, approved agent: zolbetuximab (Vyloy).[27] Developed by Astellas Pharma following its $1.4 billion acquisition of Ganymed Pharmaceuticals, zolbetuximab is a monoclonal antibody that mediates tumor cell death through ADCC and CDC.[7] Its approval was based on the positive outcomes of the Phase 3 SPOTLIGHT and GLOW trials, which established a clear efficacy benchmark in first-line G/GEJ cancer, demonstrating median PFS improvements of approximately 2-3 months and median OS improvements of approximately 3 months when added to standard chemotherapy.[13]

Zolbetuximab has secured regulatory approvals in major global markets, including Japan, the United Kingdom, the European Union, South Korea, and the United States.[27] Its journey to market, however, was not without challenges. The FDA initially issued a Complete Response Letter (CRL) in January 2024, not due to concerns with the clinical data, but because of unresolved deficiencies at a third-party manufacturing facility.[24] The issues were subsequently addressed, leading to approval in October 2024, but this event underscores the critical importance of robust Chemistry, Manufacturing, and Controls (CMC) in the successful development and launch of a biologic drug.[17]

The Broader CLDN18.2 Pipeline: A Crowded Field

The clinical validation of CLDN18.2 has catalyzed intense research and development activity, resulting in a crowded and highly competitive pipeline populated by multiple therapeutic modalities and major pharmaceutical players.[35] The landscape is rapidly evolving from the "first generation" of simple monoclonal antibodies to more potent "second-generation" approaches.

Antibody-Drug Conjugates (ADCs): This class represents the most significant competitive threat to QLS-31905. ADCs are designed to act as "biological missiles," using a monoclonal antibody to selectively deliver a potent cytotoxic payload directly to tumor cells. Several high-profile ADC programs are advancing rapidly:

• CMG-901 (AZD0901): This ADC, which uses a monomethyl auristatin E (MMAE) payload, was developed by KYM Biosciences (a joint venture of Keymed and Lepu Biopharma) and was subsequently licensed by AstraZeneca in a deal valued at over $1.1 billion.[35] It has received FDA Fast Track Designation and is currently in a Phase 3 trial.[39]
• SYSA1801 (EO-3021): Developed by CSPC Megalith Biopharmaceutical, this MMAE-based ADC was licensed to Elevation Oncology for global rights outside of Greater China in a deal worth up to $1.2 billion.[35] It has also been granted FDA Fast Track Designation.[47]
• RC118 (Ciletatug vedotin): Developed by RemeGen, RC118 has received FDA Orphan Drug Designations for both gastric and pancreatic cancer, signaling a strategic focus on these key indications.[35]
• LM-302 (TPX-4589): Originating from LaNova Medicines and licensed by Turning Point Therapeutics, this ADC has advanced into a pivotal Phase 3 trial in China.[35]
• Novel Payload ADCs: Other companies are exploring ADCs with different cytotoxic payloads, such as topoisomerase I inhibitors (e.g., SHR-A1904 and XNW27011), to potentially overcome resistance to microtubule inhibitors like MMAE.[36]

Other Bispecific Antibodies: QLS-31905 is not the only bispecific antibody in development. Other programs are exploring different co-targets to engage the immune system in alternative ways. These include Givastomig (TJ-CD4B/ABL111), which targets CLDN18.2 and the co-stimulatory molecule 4-1BB, and Q-1802, which targets CLDN18.2 and the immune checkpoint PD-L1.[37]

Chimeric Antigen Receptor T-Cell (CAR-T) Therapies: Representing a highly potent but complex therapeutic modality, several CAR-T cell therapies targeting CLDN18.2 are in early clinical development. Assets such as CT041 and LB1908 have demonstrated very high objective response rates in early-phase trials for gastric cancer.[11] However, CAR-T therapies face significant logistical challenges related to manufacturing (autologous cell collection, engineering, and re-infusion), cost, and the management of severe toxicities like CRS and neurotoxicity, which may limit their application to later lines of therapy in specialized centers.

Drug Name (Developer)	Modality	Mechanism of Action	Key Indication	Highest Development Phase	Key Reported Data
Zolbetuximab (Astellas)	Monoclonal Ab	ADCC / CDC	G/GEJ Cancer	Marketed	mPFS 10.6 mo (SPOTLIGHT) 13
QLS-31905 (Qilu)	Bispecific Ab	CD3 T-Cell Engager	Solid Tumors	Phase 1/2	ORR 25% (PAC), 15.8% (G/GEJ) 3
CMG-901 (AstraZeneca)	ADC	MMAE Payload	Solid Tumors	Phase 3	Encouraging early anti-tumor activity 40
SYSA1801 (Elevation)	ADC	MMAE Payload	Solid Tumors	Phase 1	ORR 42.8% in enriched G/GEJ subset 47
RC118 (RemeGen)	ADC	Microtubule Inhibitor	Solid Tumors	Phase 1/2	Favorable safety and tolerability 48
LM-302 (LaNova)	ADC	MMAE Payload	G/GEJ Cancer	Phase 3	ORR 30.6% in refractory G/GEJ 51
Givastomig (I-Mab)	Bispecific Ab	4-1BB Agonist	Solid Tumors	Phase 1	PRs in 16.6% of patients 37
CT041 (CARsgen)	CAR-T	T-Cell Therapy	G/GEJ Cancer	Phase 2	ORR 57.1% in gastric cancer 37
Table 3: Comparative Analysis of Key CLDN18.2-Targeted Therapies.3 Ab = Antibody; ADC = Antibody-Drug Conjugate; CAR-T = Chimeric Antigen Receptor T-Cell.

Differentiating QLS-31905

In this crowded and rapidly advancing field, QLS-31905 must establish a clear and compelling clinical differentiation. Its potential advantages are rooted in its mechanism, safety profile, and strategic indication selection. The T-cell engaging mechanism offers a mode of action distinct from both zolbetuximab's ADCC/CDC and the targeted chemotherapy delivery of ADCs. This could translate to deeper and more durable responses if T-cell memory is effectively established. The manageable CRS profile observed to date is a significant potential advantage over other T-cell engagers and could compare favorably to the systemic toxicities associated with ADC payloads (e.g., myelosuppression, neuropathy). Finally, the strong early efficacy signal in pancreatic cancer provides a clear strategic opportunity to pursue a first-in-class or best-in-class position in an indication with high unmet medical need, potentially securing a market niche before confronting competitors head-on in G/GEJ cancer.

However, the challenges are substantial. QLS-31905 faces direct competition from a wave of well-funded ADC programs backed by major pharmaceutical companies like AstraZeneca. The need to carefully manage CRS and other immune-related toxicities will remain a key focus in larger trials. Ultimately, the clinical data will determine its place. The central question is whether the direct T-cell engagement of a BiTE can outperform the cytotoxic payload delivery of an ADC in terms of the net clinical benefit, weighing both efficacy and long-term safety. The clinical outcomes for QLS-31905 will be a critical data point in determining the winning second-generation strategy for targeting CLDN18.2.

Synthesis, Unanswered Questions, and Future Outlook

Integrated Analysis of Strengths and Weaknesses

QLS-31905 emerges as a clinically promising, second-generation therapeutic agent targeting the validated antigen CLDN18.2. Its development program is underpinned by a series of strategic strengths but also faces considerable challenges and risks.

Strengths:

• Validated Target: The program targets CLDN18.2, a biomarker whose clinical relevance and druggability have been de-risked by the approval of zolbetuximab.[17]
• Potent Mechanism of Action: As a T-cell engager, QLS-31905 leverages a highly potent mechanism of action that directly harnesses the cytotoxic power of T-cells, which may lead to deep and durable responses.[1]
• Encouraging Monotherapy Efficacy: The Phase 1 trial demonstrated meaningful anti-tumor activity in a heavily pre-treated patient population, establishing clinical proof-of-concept.[3]
• Strong Signal in Pancreatic Cancer: The 25% ORR in refractory pancreatic cancer is a standout result and represents a significant opportunity in an area of high unmet medical need.[3]
• Manageable Safety Profile: The low rate of severe CRS (3.8%) and the fact that the MTD was not reached suggest a favorable therapeutic window and a potential safety advantage over other T-cell redirecting therapies.[3]
• Rapid and Pragmatic Clinical Strategy: The program has moved swiftly from monotherapy in the refractory setting to combination therapy in the first-line setting, partnering with established standards of care to accelerate development and facilitate market adoption.[5]

Weaknesses:

• Intense Competition: The CLDN18.2 space is exceptionally crowded, with an approved market leader (zolbetuximab) and a deep pipeline of well-funded competitors, particularly ADCs.[36]
• Inherent Class-Related Toxicity: While manageable to date, CRS and other immune-related adverse events remain an inherent risk of the T-cell engager class that will require careful management in larger, more diverse patient populations.
• High Efficacy Bar: In G/GEJ cancer, QLS-31905 will need to demonstrate efficacy that is at least competitive with, if not superior to, the benchmark set by zolbetuximab plus chemotherapy.[13]
• Independent Development: To date, QLS-31905 is being developed solely by Qilu Pharmaceutical without a major Western pharmaceutical partner, which could impact the scale and speed of global pivotal trials and commercialization efforts.

Key Risks and Mitigation Strategies

The future development of QLS-31905 is subject to several key risks that will require proactive management.

• Clinical Risk: The primary clinical risk is the management of immune-related toxicities, particularly CRS, in larger and more complex clinical settings. As the drug moves into Phase 2/3 trials and is combined with chemotherapy, the incidence and severity of adverse events may change. This risk is mitigated through careful trial design, including step-up dosing protocols, mandatory premedication (e.g., with corticosteroids and antihistamines), and robust patient monitoring and toxicity management guidelines.
• Competitive Risk: There is a significant risk that QLS-31905 will be outpaced or outperformed by the numerous ADC programs in development. These agents may demonstrate superior efficacy or a safety profile that is perceived as more manageable by community oncologists (e.g., predictable myelosuppression vs. unpredictable CRS). The primary mitigation strategy is the rapid and efficient execution of clinical trials to generate definitive data, coupled with a strategic focus on areas of potential differentiation, most notably pancreatic cancer.
• Regulatory and Commercial Risk: A subtle but important risk lies in the evolving biomarker landscape. The companion diagnostic for zolbetuximab uses a stringent cutoff of ≥75% of tumor cells with moderate-to-strong staining.[10] In contrast, the QLS-31905 expansion cohorts enrolled patients with a much lower cutoff of ≥1% expression.[3] This discrepancy could create challenges with regulators, who may require justification for the chosen patient population, and with clinicians, who may face confusion over different testing and scoring requirements for different drugs targeting the same biomarker. Mitigation will require early and clear communication with regulatory agencies and a well-defined biomarker strategy for pivotal trials.

Projected Developmental Pathway

Based on the current clinical strategy, the most direct path to registration for QLS-31905 is through the ongoing first-line combination studies. A successful data readout from one of the arms in the NCT06041035 trial, demonstrating a significant improvement in a key endpoint like PFS or ORR over historical controls, would provide the necessary foundation to design and launch a pivotal Phase 3 randomized controlled trial.

Given the particularly strong efficacy signal and the less competitive landscape in pancreatic cancer, a dedicated pivotal trial in this indication appears to be the most strategically sound next step. A Phase 3 study randomizing first-line, CLDN18.2-positive metastatic pancreatic cancer patients to receive either QLS-31905 plus gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone would directly address a major unmet need and could provide the fastest path to a first approval. For G/GEJ cancer, a pivotal trial would likely need to be designed as a head-to-head comparison against the zolbetuximab-plus-chemotherapy standard of care or demonstrate overwhelming efficacy in a subpopulation.

Corporate and Intellectual Property Overview

Developer Profile: Qilu Pharmaceutical Co., Ltd.

QLS-31905 is being developed by Qilu Pharmaceutical Co., Ltd., a leading, fully integrated biopharmaceutical company based in China.[32] Qilu is not a small biotech but a large, established enterprise with comprehensive capabilities spanning research, development, manufacturing, and commercialization.[32] A critical asset for its global ambitions is its manufacturing infrastructure. The company operates facilities that have received certifications from major international regulatory bodies, including the U.S. FDA, the European Medicines Agency (EMA), the PMDA of Japan, the MHRA of the UK, and the Therapeutic Goods Administration (TGA) of Australia.[57] This demonstrated compliance with global Good Manufacturing Practice (GMP) standards is a crucial capability that de-risks the CMC aspect of development and will be vital for supplying global clinical trials and, eventually, commercial markets.

Patent Portfolio

Qilu Pharmaceutical has been actively securing intellectual property rights for its CLDN18.2-targeted bispecific antibody platform. Patent application WO2023222135A1, for example, describes a method of treating solid tumors using a bispecific antibody comprising an anti-CLDN18.2 unit and a second antibody unit.[58] The claims in this application are notably broad, covering not only CD3 as the second target but also other immunomodulatory targets such as 4-1BB, PD-1, and PD-L1. This suggests that Qilu may be developing a broader platform of CLDN18.2-based multi-specific antibodies, of which QLS-31905 is the first to enter the clinic.

These patent applications have been filed in key global jurisdictions, including the United States, Europe, Japan, China, and Australia, with their legal status currently listed as pending.[58] This indicates a concerted effort to establish a robust and global patent estate to protect its innovation and support future commercialization.

Conclusion

QLS-31905 is a well-designed, second-generation bispecific T-cell engager that has demonstrated compelling proof-of-concept in early clinical trials. It targets the validated antigen CLDN18.2 with a potent mechanism of action, and its development is proceeding rapidly under a pragmatic clinical strategy. The monotherapy data are encouraging, highlighted by a manageable safety profile with a low incidence of severe Cytokine Release Syndrome and a particularly strong efficacy signal in heavily pre-treated pancreatic cancer—a key potential differentiator.

The ultimate success of QLS-31905, however, will be determined by its performance in the crucible of late-stage clinical trials and a fiercely competitive market. It must navigate a landscape defined by the approved standard of care, zolbetuximab, and a formidable pipeline of next-generation antibody-drug conjugates that are attracting massive investment. The forthcoming results from the first-line combination therapy trial (NCT06041035) will be a critical inflection point, providing the first glimpse of its efficacy and safety when integrated with standard chemotherapy. QLS-31905's ability to maintain its favorable safety profile while delivering superior or differentiated efficacy, especially in pancreatic cancer, will be the ultimate arbiter of its place in the future of CLDN18.2-targeted cancer therapy.

Works cited

1. Definition of anti-Claudin18.2/anti-CD3 bispecific antibody QLS31905 - NCI Drug Dictionary - NCI, accessed September 28, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/anti-claudin182-anti-cd3-bispecific-antibody-qls31905
2. Abstract 5551: QLS31905, an anti-claudin 18.2/CD3 bispecific antibody for claudin 18.2-positive gastric cancer | Cancer Research | American Association for Cancer Research - AACR Journals, accessed September 28, 2025, https://aacrjournals.org/cancerres/article/82/12_Supplement/5551/701368/Abstract-5551-QLS31905-an-anti-claudin-18-2-CD3
3. Safety and efficacy of QLS31905 in patients with advanced solid ..., accessed September 28, 2025, https://ascopubs.org/doi/pdf/10.1200/JCO.2025.43.16_suppl.2527
4. Qilu Pharmaceutical Announces Results from Phase I Clinical Study ..., accessed September 28, 2025, https://www.prnewswire.com/news-releases/qilu-pharmaceutical-announces-results-from-phase-i-clinical-study-for-its-novel-bispecific-antibody-qls31905-at-esmo-immuno-oncology-congress-302011984.html
5. NCT06041035 | A Study of QLS31905 Combination Chemotherapy as First-Line Treatment in Patients With Advanced Solid Tumors | ClinicalTrials.gov, accessed September 28, 2025, https://clinicaltrials.gov/study/NCT06041035
6. Zolbetuximab for Claudin18.2-positive gastric or gastroesophageal junction cancer - PMC, accessed September 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10768589/
7. VYLOY® (zolbetuximab-clzb) Mechanism of Action, accessed September 28, 2025, https://www.vyloyhcp.com/mechanism-of-action
8. Dark horse target Claudin18.2 opens new battlefield for pancreatic cancer - PMC, accessed September 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10951399/
9. Zolbetuximab: Uses in Cancer, Side Effects, Dosages, Expectations, and More - Oncodaily, accessed September 28, 2025, https://oncodaily.com/drugs/zolbetuximab-vyloy-overview
10. What Community Oncologists Should Know About Claudin 18.2 and Its Role in Gastric Cancer, accessed September 28, 2025, https://www.oncologynewscentral.com/gastric-cancer/what-community-oncologists-should-know-about-claudin-18-2-and-its-role-in-gastric-cancer
11. Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy - PubMed, accessed September 28, 2025, https://pubmed.ncbi.nlm.nih.gov/35642043/
12. Claudin 18.2: An attractive marker in pancreatic ductal adenocarcinoma, accessed September 28, 2025, https://www.spandidos-publications.com/10.3892/ol.2025.14886
13. Astellas to Present Positive Findings from Phase 3 SPOTLIGHT Trial of Zolbetuximab during 2023 ASCO GI Cancers Symposium, accessed September 28, 2025, https://newsroom.astellas.us/2023-01-19-Astellas-to-Present-Positive-Findings-from-Phase-3-SPOTLIGHT-Trial-of-Zolbetuximab-during-2023-ASCO-GI-Cancers-Symposium
14. Astellas Receives Approval from the European Commission for VYLOY™ (zolbetuximab) in Combination with Chemotherapy for Advanced Gastric and Gastroesophageal Junction Cancer - PR Newswire, accessed September 28, 2025, https://www.prnewswire.com/news-releases/astellas-receives-approval-from-the-european-commission-for-vyloy-zolbetuximab-in-combination-with-chemotherapy-for-advanced-gastric-and-gastroesophageal-junction-cancer-302254213.html
15. Zolbetuximab plus gemcitabine and nab-paclitaxel (GN) in first-line treatment of claudin 18.2-positive metastatic pancreatic cancer (mPC): Phase 2, open-label, randomized study. - ASCO, accessed September 28, 2025, https://www.asco.org/abstracts-presentations/ABSTRACT370612
16. Claudin 18.2 & Testing Resources | VYLOY® (zolbetuximab-clzb), accessed September 28, 2025, https://www.vyloyhcp.com/cldn182-and-testing
17. FDA approves zolbetuximab-clzb with chemotherapy for gastric or gastroesophageal junction adenocarcinoma, accessed September 28, 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zolbetuximab-clzb-chemotherapy-gastric-or-gastroesophageal-junction-adenocarcinoma
18. Claudin18.2 (CLDN18.2) expression and efficacy in pancreatic ductal adenocarcinoma (PDAC): Results from a phase I dose expansion cohort evaluating IBI343. - ASCO Publications, accessed September 28, 2025, https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4017
19. A First-in-class Targeted Therapy for Some Gastrointestinal Cancers, accessed September 28, 2025, https://www.aacr.org/patients-caregivers/progress-against-cancer/a-first-in-class-targeted-therapy-for-some-gastrointestinal-cancers/
20. www.cancernetwork.com, accessed September 28, 2025, https://www.cancernetwork.com/view/efficacy-and-safety-of-zolbetuximab-in-gastric-cancer#:~:text=Zolbetuximab%2C%20an%20anti%2DCLDN18.,%2Ddependent%20cytotoxicity%20(CDC).
21. Efficacy and Safety of Zolbetuximab in Gastric Cancer - CancerNetwork, accessed September 28, 2025, https://www.cancernetwork.com/view/efficacy-and-safety-of-zolbetuximab-in-gastric-cancer
22. What is the mechanism of Zolbetuximab? - Patsnap Synapse, accessed September 28, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-zolbetuximab
23. Characterization of zolbetuximab in pancreatic cancer models - Taylor & Francis Online, accessed September 28, 2025, https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1523096
24. FDA Acknowledges BLA of Zolbetuximab in HER2–, CLDN18.2+ Gastric/GEJ Cancer, accessed September 28, 2025, https://www.targetedonc.com/view/fda-acknowledges-bla-of-zolbetuximab-in-her2--cldn18-2-gastric-gej-cancer
25. A New Targeted Treatment Shows Promise for Select Patients with Stomach Cancer, accessed September 28, 2025, https://meyercancer.weill.cornell.edu/news/2023-08-23/new-targeted-treatment-shows-promise-select-patients-stomach-cancer
26. FDA Approves Zolbetuximab Plus Chemo for CLDN18.2+ Gastric or GEJ Adenocarcinoma, accessed September 28, 2025, https://www.onclive.com/view/fda-approves-zolbetuximab-plus-chemo-for-cldn18-2-gastric-or-gej-adenocarcinoma
27. Astellas' VYLOY™ (zolbetuximab-clzb) Approved by U.S. FDA for Treatment of Advanced Gastric and GEJ Cancer - PR Newswire, accessed September 28, 2025, https://www.prnewswire.com/news-releases/astellas-vyloy-zolbetuximab-clzb-approved-by-us-fda-for-treatment-of-advanced-gastric-and-gej-cancer-302280716.html
28. NCT05278832 | A Study of QLS31905 in Patients With Advanced Solid Tumors | ClinicalTrials.gov, accessed September 28, 2025, https://clinicaltrials.gov/study/NCT05278832
29. Qilu Pharmaceutical Announces Results from Phase I Clinical Study for Its Novel Bispecific Antibody QLS31905 at ESMO Immuno-Oncology Congress - BioSpace, accessed September 28, 2025, https://www.biospace.com/qilu-pharmaceutical-announces-results-from-phase-i-clinical-study-for-its-novel-bispecific-antibody-qls31905-at-esmo-immuno-oncology-congress
30. Study Details | NCT07066995 | Mesothelin and Claudin 18.2 Dual-Target CAR-T Therapy in Advanced Pancreatic Cancer | ClinicalTrials.gov, accessed September 28, 2025, https://clinicaltrials.gov/study/NCT07066995
31. Pharmacokinetics: Definition & Use in Drug Development - Allucent, accessed September 28, 2025, https://www.allucent.com/resources/blog/what-pharmacokinetics-and-adme
32. A Study of QLS31905 Combination Chemotherapy as - ClinConnect, accessed September 28, 2025, https://clinconnect.io/trials/NCT06041035
33. CLDN18.2 x CD3 - Drugs, Indications, Patents - Patsnap Synapse, accessed September 28, 2025, https://synapse.patsnap.com/target/3c8cf2172ccd3841ab68420037e570e0
34. FDA rejects Astellas' zolbetuximab for manufacturing issues - Fierce Pharma, accessed September 28, 2025, https://www.fiercepharma.com/pharma/astellas-gastric-cancer-candidate-rejected-fda-because-manufacturing-issues
35. ADC Drugs Targeting Claudin18.2 - Biopharma PEG, accessed September 28, 2025, https://www.biochempeg.com/article/345.html
36. Claudin 18.2-Directed Oncology Therapeutics--A Fast-Growing Market with Blockbuster Potential | DelveInsight, accessed September 28, 2025, https://www.prnewswire.com/news-releases/claudin-18-2-directed-oncology-therapeuticsa-fast-growing-market-with-blockbuster-potential--delveinsight-302511738.html
37. Claudin 18.2: A Promising New Target for Breakthrough Cancer Treatments, accessed September 28, 2025, https://www.biochempeg.com/article/414.html
38. Claudin18.2-targeted cancer theranostics - PMC, accessed September 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10193197/
39. CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors, accessed September 28, 2025, https://pubmed.ncbi.nlm.nih.gov/39232496/
40. License agreement with KYM Biosciences for CMG901, a Claudin-18.2 antibody drug conjugate, completed - AstraZeneca, accessed September 28, 2025, https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-completes-agreement-with-kym-for-cmg901.html
41. AstraZeneca enters license agreement with KYM Biosciences for CMG901, a Claudin-18.2 antibody drug conjugate, accessed September 28, 2025, https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-enters-license-agreement-with-kym-biosciences-for-cmg901-a-claudin-182-antibody-drug-conjugate.html
42. Antibody conjugate CMG901 receives fast track designation by FDA for patients with gastric cancers - BJMO, accessed September 28, 2025, https://www.bjmo.be/antibody-conjugate-cmg901-receives-fast-track-designation-by-fda-for-patients-with-gastric-cancers/
43. SYSA-1801 - Drug Targets, Indications, Patents - Patsnap Synapse, accessed September 28, 2025, https://synapse.patsnap.com/drug/62d8b1e0a5124aef97d8d69d1a860b53
44. CSPC grants Elevation Oncology global rights to ADC drug in $1.2B deal | BioWorld, accessed September 28, 2025, https://www.bioworld.com/articles/521123-cspc-grants-elevation-oncology-global-rights-to-adc-drug-in-12b-deal
45. VOLUNTARY ANNOUNCEMENT EXCLUSIVE LICENSE AGREEMENT FOR SYSA1801 WITH ELEVATION ONCOLOGY, INC. - Irasia, accessed September 28, 2025, https://doc.irasia.com/listco/hk/cspc/announcement/a220728.pdf
46. Elevation Oncology Expands Pipeline through Exclusive Licensing of EO-3021 (SYSA1801), a Clinical Stage Anti-Claudin18.2 Antibody Drug Conjugate, From CSPC Pharmaceutical Group - PR Newswire, accessed September 28, 2025, https://www.prnewswire.com/news-releases/elevation-oncology-expands-pipeline-through-exclusive-licensing-of-eo-3021-sysa1801-a-clinical-stage-anti-claudin18-2-antibody-drug-conjugate-from-cspc-pharmaceutical-group-301595313.html
47. FDA Grants Fast Track Status to EO-3021 for CLDN18.2-Expressing Gastric or GEJ Cancer, accessed September 28, 2025, https://www.onclive.com/view/fda-grants-fast-track-status-to-eo-3021-for-cldn18-2-expressing-gastric-or-gej-cancer
48. RemeGen RC118 phase I clinical study shows favorable safety and tolerability, accessed September 28, 2025, https://remegen.com/index.php?v=show&cid=115&id=976
49. RC 118 - AdisInsight - Springer, accessed September 28, 2025, https://adisinsight.springer.com/drugs/800057322
50. RemeGen's RC118 granted two orphan drug designations by FDA - Pharmafile, accessed September 28, 2025, https://pharmafile.com/news/remegen-s-rc118-granted-two-orphan-drug-designations-fda/
51. Novel Claudin18.2-Targeted Therapies in Gastrointestinal Tumors | ACS Omega, accessed September 28, 2025, https://pubs.acs.org/doi/10.1021/acsomega.5c06506
52. Publications-LaNova Medicines, accessed September 28, 2025, https://www.lanovamedicines.com/en/our-science/publications-presentations/lm-302
53. Turning Point Therapeutics Announces Pipeline Expansion, Licensing of TPX-4589 (LM-302), A Clinical Stage Anti-Claudin18.2 Antibody Drug Conjugate for Gastrointestinal Cancers, From Lanova Medicines - BioSpace, accessed September 28, 2025, https://www.biospace.com/turning-point-therapeutics-announces-pipeline-expansion-licensing-of-tpx-4589-lm-302-a-clinical-stage-anti-claudin18-2-antibody-drug-conjugate-for-gastrointestinal-cancers-from-lanova-medicines
54. LaNova Medicines Initiates First Phase III Clinical Trial for LM-302 in China, accessed September 28, 2025, https://www.lanovamedicines.com/en/news-center/press-release/68.html
55. LaNova Medicines and Turning Point Therapeutics Enter Into a Licensing Agreement for LM-302, accessed September 28, 2025, http://www.lanovamedicines.com/en/news-center/press-release/55.html
56. QLS31905 / Qilu Pharma - LARVOL DELTA, accessed September 28, 2025, https://delta.larvol.com/Products/?ProductId=cea337c3-df01-42b5-9798-d8b5ebc84c22
57. QLS-31905 by Qilu Pharmaceutical for Pancreatic Cancer: Likelihood of Approval, accessed September 28, 2025, https://www.pharmaceutical-technology.com/data-insights/qls-31905-qilu-pharmaceutical-pancreatic-cancer-likelihood-of-approval/
58. WO2023222135A1 - A method of treating solid tumor - Google Patents, accessed September 28, 2025, https://patents.google.com/patent/WO2023222135A1/en
59. AU2023291843A1 - Anti-cldn18.2 antibody, and pharmaceutical composition and use thereof - Google Patents, accessed September 28, 2025, https://patents.google.com/patent/AU2023291843A1/en