Report on Sevabertinib (BAY-2927088): A Novel Tyrosine Kinase Inhibitor for HER2-Altered Malignancies

I. Executive Summary

Sevabertinib, also known by its development code BAY-2927088, is an investigational, orally administered, small molecule therapy developed by Bayer that represents a significant advancement in the field of precision oncology. Classified as a reversible tyrosine kinase inhibitor (TKI), sevabertinib is engineered to potently and selectively target tumors driven by activating mutations in the Human Epidermal Growth Factor Receptor 2 (HER2) and the Epidermal Growth Factor Receptor (EGFR). The primary focus of its development has been non-small cell lung cancer (NSCLC), a setting where HER2 mutations define a patient subpopulation with a historically poor prognosis and limited targeted treatment options.

Clinical data from the foundational Phase I/II SOHO-01 trial have demonstrated a compelling efficacy profile. In heavily pretreated patients with HER2-mutant NSCLC, sevabertinib has achieved high objective response rates (ORRs) ranging from approximately 60% to over 70%, with durable responses and high rates of disease control. Remarkably, similar efficacy has been observed in the first-line setting, suggesting a potent anti-tumor activity that is consistent across different stages of treatment.

Equally significant is sevabertinib's manageable and differentiated safety profile. While exhibiting class-effect toxicities such as diarrhea and rash, these adverse events are predominantly low-grade and can be managed with supportive care and dose modifications. Critically, clinical studies to date have reported no instances of interstitial lung disease (ILD) or pneumonitis, a serious and potentially fatal toxicity associated with other HER2-directed therapies, including the current standard of care, trastuzumab deruxtecan (T-DXd). This favorable safety profile, combined with the convenience of oral administration, positions sevabertinib as a potentially superior therapeutic option.

Recognizing its potential to address a significant unmet medical need, the U.S. Food and Drug Administration (FDA) has granted sevabertinib both Breakthrough Therapy Designation and Priority Review, expediting its path toward potential approval. With a pivotal Phase III trial underway to establish its role in the first-line setting and a Phase II basket trial exploring its activity across a range of other HER2-mutant solid tumors, sevabertinib is poised to not only challenge the current treatment paradigm in NSCLC but also to potentially emerge as a new standard of care for a genetically defined patient population across multiple cancer types.

II. Introduction to Sevabertinib and the Unmet Need in HER2-Mutant Cancers

Drug Profile and Development

Sevabertinib (BAY-2927088) is an innovative, investigational small molecule being developed by the global pharmaceutical company Bayer.[1] The compound originated from a strategic research collaboration between Bayer, the Broad Institute of MIT and Harvard, and the Dana-Farber Cancer Institute, combining academic discovery with pharmaceutical development expertise.[3] Chemically, it is classified as an oral, reversible tyrosine kinase inhibitor (TKI), a class of drugs designed to block specific enzymes that are critical for cancer cell growth and proliferation.[6] Its formulation as an oral tablet offers a significant quality-of-life advantage over intravenously administered alternatives, allowing for at-home treatment and reducing the burden on both patients and healthcare infrastructure.[2]

The Therapeutic Target: HER2-Activating Mutations

The clinical development of sevabertinib is rooted in the principles of precision medicine, targeting tumors with specific genetic alterations. Its primary targets are activating mutations in the ERBB2 gene, which encodes the Human Epidermal Growth Factor Receptor 2 (HER2) protein.[10] HER2 is a member of the EGFR family of receptor tyrosine kinases, which play a fundamental role in regulating normal cell growth, division, and survival.[12]

In certain cancers, mutations in the ERBB2 gene lead to the production of an abnormal HER2 protein that is constitutively active, meaning it continuously sends growth signals without external stimulation. This aberrant signaling drives uncontrolled cell proliferation and tumor progression, making the HER2 mutation an oncogenic driver.[10] In non-small cell lung cancer, activating HER2 mutations are identified in approximately 2-4% of patients, predominantly in the adenocarcinoma subtype and often in individuals with a limited or non-existent smoking history.[5] The most common of these alterations are in-frame insertions within exon 20 of the gene's tyrosine kinase domain, which are associated with a particularly poor prognosis and historical resistance to earlier-generation TKIs.[13]

The Unmet Medical Need and Current Standard of Care

For decades, patients with HER2-mutant NSCLC faced a significant therapeutic void, as there were no approved targeted therapies for this specific molecular subtype.[18] The standard of care (SoC) for the first-line treatment of advanced disease has been platinum-based chemotherapy, often in combination with an immune checkpoint inhibitor.[13] While this regimen provides some benefit, its efficacy is limited, with studies showing ORRs of approximately 36% and a median progression-free survival (PFS) of only around 5 months.[19]

The treatment landscape for previously treated patients was transformed by the approval of the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd). T-DXd has demonstrated significant efficacy and is now the preferred second-line option.[20] However, its use is associated with a substantial toxicity burden. Most notably, T-DXd carries a black box warning for the risk of severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis, a condition of particular concern in a lung cancer patient population.[17] This creates a pressing unmet medical need for novel therapies that can either improve upon the efficacy of first-line chemotherapy or offer a safer, more tolerable alternative to T-DXd in the second-line setting. It is this well-defined clinical gap that sevabertinib is being developed to address.[6]

III. Molecular Mechanism of Action and Preclinical Evidence

Potent and Selective Dual-Target Inhibition

Sevabertinib is engineered as a highly potent and selective inhibitor of the signaling pathways driven by mutant forms of both HER2 and EGFR.[2] Its mechanism is centered on blocking the adenosine triphosphate (ATP) binding site within the kinase domain of these receptors, thereby preventing the downstream signaling cascades that lead to cancer cell proliferation and survival.[1] The drug's activity is specifically directed against key oncogenic driver mutations, including HER2 exon 20 insertions and various HER2 point mutations, as well as EGFR exon 20 insertions.[6]

A defining characteristic of sevabertinib's molecular profile is its high degree of selectivity for mutant receptors over their wild-type (WT) counterparts.[7] Preclinical data have shown that sevabertinib inhibits EGFR with exon 20 insertions at concentrations 40-fold lower than those required to inhibit WT EGFR.[15] This high selectivity is crucial for establishing a favorable therapeutic window. By preferentially targeting the mutated proteins that drive the cancer while largely sparing the normal proteins present in healthy tissues, the drug can achieve a potent anti-tumor effect at doses that minimize mechanism-based, on-target toxicities, such as the skin rash and diarrhea commonly associated with non-selective EGFR inhibition.

Structural Basis for Improved Therapeutic Window and Overcoming Resistance

Sevabertinib functions as a reversible and non-covalent TKI, a design choice with profound clinical implications.[7] Unlike covalent inhibitors that form a permanent bond with a cysteine residue in the kinase domain, sevabertinib's binding is transient. This non-covalent binding mode is the key to its activity against the EGFR C797S mutation.[7] The C797S mutation, which substitutes the target cysteine residue with a serine, is a well-established mechanism of acquired resistance to third-generation covalent EGFR inhibitors (e.g., osimertinib) because it physically prevents the formation of the covalent bond. By not relying on this specific interaction, sevabertinib retains its potent inhibitory activity in the presence of C797S, offering a potential treatment option for patients who have progressed on other EGFR TKIs due to this specific resistance mechanism.[9] This molecular design reflects a sophisticated approach, learning from the clinical limitations of prior generations of TKIs to address a known pathway of treatment failure proactively.

Preclinical Validation

The therapeutic hypothesis behind sevabertinib was validated in rigorous preclinical studies. In patient-derived xenograft (PDX) models, where human tumor tissue is implanted into immunodeficient mice, sevabertinib demonstrated strong, dose-dependent inhibition of tumor growth.[15] These studies confirmed its potent in vivo activity in models harboring clinically relevant mutations, including NSCLC with EGFR exon 20 insertions and models carrying the EGFR C797S acquired resistance mutation.[15] The robust anti-tumor activity and high selectivity observed in these preclinical experiments provided a strong scientific rationale for advancing sevabertinib into clinical trials in humans.[1]

IV. The Sevabertinib Clinical Development Program: A Multi-Pronged Strategy

The clinical development of sevabertinib has been executed through a comprehensive and strategically aggressive program designed to rapidly establish its efficacy and safety, secure regulatory approval, and explore its full therapeutic potential across multiple indications. This multi-pronged strategy underscores Bayer's confidence in the asset.

Phase I/II: The SOHO-01 Trial (NCT05099172)

The cornerstone of the program is the SOHO-01 study, a first-in-human, open-label, multicenter Phase I/II trial.[6] This foundational study was designed not only to assess the safety, tolerability, and pharmacokinetics (PK) of sevabertinib but also to obtain early signals of its anti-tumor efficacy. The trial features a sophisticated, adaptive design composed of several parts:

• Dose Escalation: This initial phase enrolled patients with advanced NSCLC harboring either EGFR or HER2 mutations to determine the maximum tolerated dose (MTD) and establish the recommended Phase 2 dose (RP2D). This dose was identified as 20 mg administered orally twice daily.[8]
• Backfill Cohorts: As safe and potentially effective dose levels were cleared, additional patients were enrolled in backfill cohorts to gather more robust safety and PK data, allowing for a more confident selection of the optimal dose.[12]
• Expansion and Extension Cohorts: Once the RP2D was established, the trial moved into expansion phases, enrolling patients into well-defined cohorts based on their specific cancer type, genetic mutation, and prior treatment history. These cohorts are designed to rigorously evaluate the drug's efficacy in specific target populations. Notable cohorts include Cohort D, for patients with pre-treated HER2-mutant NSCLC who are naïve to other HER2-targeted therapies, and Cohort F, for treatment-naïve (first-line) patients with HER2-mutant NSCLC.[8]

Phase III: The SOHO-02 Trial (NCT06452277)

Building on the promising results from SOHO-01, Bayer has initiated the SOHO-02 study, a global, pivotal Phase III trial intended to support full regulatory approval in the first-line setting.[10] This open-label, randomized, active-controlled trial is designed to directly compare the efficacy and safety of sevabertinib against the current standard of care for treatment-naïve patients with locally advanced or metastatic non-squamous NSCLC harboring HER2-activating mutations.[10] In the trial, patients are randomized to receive either oral sevabertinib (20 mg twice daily) or the standard regimen of platinum-based doublet chemotherapy (cisplatin or carboplatin plus pemetrexed) combined with the immune checkpoint inhibitor pembrolizumab.[10] The primary endpoint of the study is Progression-Free Survival (PFS) as assessed by a blinded independent central review (BICR), the gold standard for regulatory submissions.[27]

Phase II Basket Trial: The panSOHO Study (NCT06760819)

In a clear demonstration of a broader strategic vision, Bayer is simultaneously investigating sevabertinib's potential beyond NSCLC in the panSOHO study.[11] This Phase II, open-label, single-arm "basket" trial is enrolling patients with a variety of metastatic or unresectable solid tumors that all share a common molecular feature: an activating HER2 mutation.[11] The trial is designed to assess sevabertinib in tumor types such as colorectal, biliary tract, bladder, cervical, and endometrial cancers, among others.[11] The primary endpoint is ORR by BICR, a signal-seeking objective designed to quickly identify tumor types where the drug has meaningful activity.[29] This parallel development approach is highly strategic; it aims to maximize the drug's value by pursuing a potential tumor-agnostic label based on the HER2 biomarker, which could open up multiple accelerated regulatory pathways independent of the outcome in first-line NSCLC.

Phase I Drug-Interaction Study (NCT06329895)

To ensure the safe use of sevabertinib in a real-world setting where patients are often taking multiple medications, a dedicated Phase I drug-drug interaction study is being conducted in healthy volunteers.[32] This study aims to characterize sevabertinib's potential to inhibit key drug transporter proteins, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), by measuring its effect on the pharmacokinetics of known substrate drugs (dabigatran and rosuvastatin). The results are essential for providing guidance on managing potential interactions with commonly co-administered medicines.[32]

V. Clinical Efficacy in HER2-Mutant Non-Small Cell Lung Cancer

The clinical efficacy of sevabertinib in patients with HER2-mutant NSCLC has been evaluated primarily in the expansion cohorts of the Phase I/II SOHO-01 trial, with results demonstrating consistently high levels of anti-tumor activity.

Efficacy in Pretreated Patients (SOHO-01, Cohort D)

Cohort D of the SOHO-01 study enrolled patients with advanced HER2-mutant NSCLC who had experienced disease progression after receiving at least one prior line of systemic therapy but had not been treated with a prior HER2-targeted agent.[8] This population represents a significant unmet need, where subsequent treatment options are limited.

Multiple analyses from this cohort have yielded impressive results. Data presented at the 2024 IASLC World Conference on Lung Cancer, based on an analysis of 44 patients, showed a confirmed Objective Response Rate (ORR) of 72.1% (95% CI, 56.3%-84.7%).[8] This included one patient (2.3%) with a complete response (CR) and 31 patients (69.8%) with a partial response (PR). The Disease Control Rate (DCR), representing the percentage of patients achieving either a response or stable disease, was 83.7%.[8] A later analysis with a data cutoff of October 14, 2024, which included a larger set of 81 patients, reported a consistent investigator-assessed

ORR of 59.3% and a DCR (defined as response or stable disease for ≥12 weeks) of 84.0%.[25]

The responses observed are not only frequent but also durable. The median Duration of Response (DoR) has been reported as 8.7 months, with a median Progression-Free Survival (PFS) of 7.5 months in the earlier analysis.[8] These efficacy metrics are highly encouraging in a pretreated patient population.

Efficacy in the First-Line Setting (SOHO-01, Cohort F)

To evaluate its potential as an initial therapy, Cohort F enrolled treatment-naïve patients with locally advanced or metastatic HER2-mutant NSCLC.[25] The results from this cohort are particularly striking for their similarity to those seen in pretreated patients, suggesting that sevabertinib's potent activity is not diminished in the first-line setting. The analysis with the October 14, 2024, data cutoff, based on 39 patients, showed an investigator-assessed

ORR of 59.0% and a DCR of 84.6%.[25] This high level of activity in treatment-naïve patients provides a strong rationale for the ongoing Phase III SOHO-02 trial, which aims to establish sevabertinib as a new first-line standard of care.

Efficacy in Specific Subgroups

The anti-tumor activity of sevabertinib appears particularly pronounced in patients whose tumors harbor HER2 exon 20 insertions, which represent the most common and historically difficult-to-treat type of HER2 mutation in NSCLC.[8] One report from the SOHO-01 trial highlighted an exceptional

ORR of 90% and a DCR of 97% specifically within this patient subgroup, indicating a profound level of efficacy against this key oncogenic driver.[8]

Efficacy Endpoint	Cohort D (Pretreated, n=81)	Cohort F (First-Line, n=39)
Investigator-Assessed ORR	59.3% (95% CI: 47.8, 70.1)	59.0% (95% CI: 42.1, 74.4)
**Disease Control Rate (DCR)**¹	84.0% (95% CI: 74.1, 91.2)	84.6% (95% CI: 69.5, 94.1)
Complete Response (CR)	1.2% (1 patient)	0%
Partial Response (PR)	58.0%	59.0%
Stable Disease (SD)	27.2%	25.6%
Progressive Disease (PD)	12.3%	12.8%
¹ DCR defined as confirmed response or stable disease for ≥12 weeks.
Table 1: Summary of Efficacy Results from Key SOHO-01 Cohorts (Data Cutoff: Oct 14, 2024) 25

VI. Comprehensive Safety and Tolerability Analysis

A thorough evaluation of a new cancer therapy requires a balanced assessment of both its efficacy and its safety profile. Clinical data from the SOHO-01 trial indicate that sevabertinib possesses a manageable and predictable safety profile, which is a critical attribute for any therapy intended for long-term administration.

Overall Adverse Event Profile

Treatment-related adverse events (TRAEs) are frequently observed with sevabertinib, occurring in over 96% of patients across study cohorts.[8] However, the vast majority of these events are low-grade (Grade 1 or 2) and do not pose a serious risk to patients.[8] More significant, Grade 3 or higher TRAEs, have been reported in 38.3% of patients in the larger pretreated cohort (Cohort D) and in a lower proportion, 20.5%, of patients in the first-line cohort (Cohort F).[25]

Most Common Treatment-Related Adverse Events

The pattern of adverse events is consistent with the known toxicities of the TKI drug class, particularly those that inhibit the EGFR/HER2 pathway.

• Diarrhea: This is the most common TRAE, reported in approximately 82-84% of patients. However, it is predominantly Grade 1-2 in severity. Grade 3 or higher diarrhea is substantially less frequent, occurring in 23.5% of patients in Cohort D and only 2.6% (one patient) in Cohort F.[8]
• Rash: Skin rash is the second most common TRAE, affecting around 49-56% of patients. Importantly, these events have been almost exclusively Grade 1-2, with no Grade ≥3 rash reported in the key cohorts.[25]
• Other Common Events: Other TRAEs occurring in ≥20% of patients include paronychia (inflammation of the skin around the nails) and stomatitis (mouth sores).[25]

Management and Discontinuation Rates

The tolerability of sevabertinib is further supported by the low rates of treatment discontinuation due to adverse events. While dose reductions and interruptions are utilized to manage toxicities—with diarrhea being the most common reason for a dose reduction—these strategies appear effective in allowing patients to remain on therapy.[16] In a key finding, no patients in the reported cohorts had to permanently discontinue sevabertinib due to diarrhea.[16]

The Key Safety Differentiator: Absence of Interstitial Lung Disease

Perhaps the most significant aspect of sevabertinib's safety profile is the complete absence of a specific, highly concerning toxicity. Across all publicly reported data from the SOHO-01 trial, there have been no cases of drug-related interstitial lung disease (ILD) or pneumonitis.[16] This is a profound and critical point of differentiation from other HER2-targeted therapies, particularly the ADC T-DXd, for which ILD is a major dose-limiting toxicity that can be fatal. The lack of this pulmonary toxicity signal with sevabertinib represents a major potential safety advantage, especially for a drug intended to treat lung cancer.

Treatment-Related Adverse Event (TRAE)	Cohort D (Pretreated, n=81)	Cohort F (First-Line, n=39)
	All Grades (%)	Grade ≥3 (%)
Any TRAE	96.3	38.3
Diarrhea	84.0	23.5
Rash	49.4	0
Paronychia	24.7	0
Stomatitis	18.5	1.2
Table 2: Summary of Common Treatment-Related Adverse Events (TRAEs) from SOHO-01 25

VII. Regulatory Trajectory and Market Positioning

Accelerated Development Pathway

The promising clinical profile of sevabertinib has enabled an accelerated development and review timeline, facilitated by key designations from regulatory authorities. On February 26, 2024, Bayer announced that the U.S. FDA had granted Breakthrough Therapy Designation to sevabertinib for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy.[5] This designation is reserved for drugs that have shown preliminary clinical evidence of substantial improvement over available therapies for serious conditions, and it allows for more intensive FDA guidance and a potentially expedited review.[7]

Building on this momentum, on May 28, 2025, Bayer confirmed that the FDA had accepted its New Drug Application (NDA) for sevabertinib in this indication and granted it Priority Review.[3] A Priority Review designation shortens the FDA's review clock from the standard 10 months to 6 months, signaling the agency's belief that the drug, if approved, would offer a significant improvement in the treatment of a serious condition. Sevabertinib has also received Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China, highlighting its global potential.[16] No information regarding a regulatory submission to the European Medicines Agency (EMA) was available in the analyzed materials.[37]

Competitive Landscape Analysis: Sevabertinib vs. Trastuzumab Deruxtecan

In the second-line setting for HER2-mutant NSCLC, the primary competitor and current standard of care is the antibody-drug conjugate trastuzumab deruxtecan (T-DXd, brand name Enhertu). T-DXd gained accelerated approval based on the robust efficacy demonstrated in the DESTINY-Lung series of clinical trials.[17] A direct comparison of the clinical profiles of sevabertinib and T-DXd reveals a compelling competitive dynamic.

• Efficacy Comparison: In the pivotal DESTINY-Lung02 trial, T-DXd demonstrated a confirmed ORR of 49.0% at its approved 5.4 mg/kg dose.[23] The ORRs reported for sevabertinib in the SOHO-01 trial, ranging from 59.3% to 72.1% in a similar pretreated population, appear highly competitive and potentially numerically superior.[8] While cross-trial comparisons must be made with caution, the data suggest that sevabertinib's efficacy is, at a minimum, on par with the current standard.
• Safety Comparison: This is the most critical area of differentiation. T-DXd is associated with a significant risk of ILD/pneumonitis, which occurred in 12.9% to 14.9% of patients receiving the 5.4 mg/kg dose in DESTINY-Lung02, including fatal events.[17] In stark contrast, no cases of ILD/pneumonitis have been reported for sevabertinib, representing a profound potential safety advantage.[16]
• Administration and Convenience: Sevabertinib is an oral tablet taken twice daily at home, whereas T-DXd is administered as an intravenous infusion in a clinical setting every three weeks.[10] The convenience of an oral therapy significantly reduces the treatment burden for patients and may be a strong driver of physician and patient preference.

Attribute	Sevabertinib (BAY-2927088)	Trastuzumab Deruxtecan (T-DXd)
Drug Class	Small Molecule Tyrosine Kinase Inhibitor (TKI)	Antibody-Drug Conjugate (ADC)
Mechanism	Reversible inhibitor of mutant HER2/EGFR kinase activity	Anti-HER2 antibody linked to a topoisomerase I inhibitor payload
Administration	Oral tablet, twice daily	Intravenous (IV) infusion, every 3 weeks
Key Trial	SOHO-01 (Phase I/II)	DESTINY-Lung02 (Phase II)
Objective Response Rate (ORR)	~59% - 72%	49.0% (at 5.4 mg/kg dose)
Median Duration of Response (DoR)	8.7 months (preliminary)	16.8 months
Key Safety Concern	Diarrhea, Rash (mostly low-grade)	Interstitial Lung Disease (ILD) / Pneumonitis (~13-15% incidence, potentially fatal)
Table 3: Comparative Profile in Pretreated HER2-Mutant NSCLC 8

VIII. Future Outlook and Expert Synthesis

Anticipated Milestones and Market Impact

The development trajectory for sevabertinib is approaching several critical inflection points. The most immediate and significant milestone is the anticipated regulatory decision from the U.S. FDA, which is expected in the near future given the Priority Review status of the NDA for second-line HER2-mutant NSCLC. An approval in this setting would immediately establish sevabertinib as a major new therapeutic option, directly challenging the current standard of care.

Looking further ahead, the readout from the pivotal Phase III SOHO-02 trial will be transformative. A positive result, demonstrating superiority or non-inferiority with a better safety profile compared to first-line chemo-immunotherapy, would have the potential to displace the current standard and establish sevabertinib as the foundational treatment for all newly diagnosed patients with HER2-mutant NSCLC.

Potential for Broader Application: The Tumor-Agnostic Strategy

The ongoing panSOHO basket trial is a key element of Bayer's long-term strategy for sevabertinib and represents a significant potential value driver. HER2-activating mutations, while rare, occur across a wide spectrum of solid tumors. Positive efficacy signals from one or more cohorts in this trial could pave the way for a tumor-agnostic approval—an indication based on the presence of the HER2 biomarker, regardless of the cancer's tissue of origin. Such an approval would dramatically expand the drug's commercial potential and solidify its role as a key agent in the precision oncology armamentarium.

Concluding Assessment and Synthesis

Sevabertinib (BAY-2927088) has emerged as a highly promising investigational agent with a clinical profile that suggests it could significantly improve outcomes for patients with HER2-mutant malignancies.

Strengths:

• Potent Efficacy: Demonstrates high and durable response rates in both treatment-naïve and pretreated NSCLC patients.
• Differentiated Safety: A manageable toxicity profile highlighted by the conspicuous absence of the ILD/pneumonitis risk that plagues its main competitor.
• Oral Administration: Offers a substantial convenience and quality-of-life advantage over intravenous therapies.
• Intelligent Design: Its non-covalent mechanism provides a built-in strategy to overcome a key pathway of acquired resistance to other TKIs.

Weaknesses and Unknowns:

• Investigational Status: As the drug is not yet approved, its real-world effectiveness and safety remain to be confirmed.
• Immature Survival Data: While response rates are impressive, long-term data on key endpoints like Overall Survival (OS) are still maturing.
• Pivotal Trial Readout: The ultimate confirmation of its role, particularly in the first-line setting, is contingent on the results of the randomized Phase III SOHO-02 trial.

In conclusion, sevabertinib is not merely an incremental advance in cancer therapy. Its unique combination of high efficacy, a superior safety profile concerning pulmonary toxicity, and the convenience of oral administration positions it as a potential paradigm-shifting treatment. Should the data from its ongoing pivotal trials confirm the remarkable promise shown in early-phase studies, sevabertinib is on a clear trajectory to become a new standard of care and a cornerstone therapy for patients with HER2-mutant NSCLC and potentially a range of other solid tumors.

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