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Evaluating BAY 2927088 for Advanced Lung Cancer with HER2 Mutations

A Phase 3 Open-label, Randomized, Active-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Orally Administered BAY 2927088 Compared With Standard of Care as a First-line Therapy in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) With HER2-activating Mutations

Phase 3 Interventional Bayer · NCT06452277

This study is testing a new drug called BAY 2927088 to see if it can help people with advanced lung cancer that has specific HER2 mutations feel better compared to standard treatments.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment444 (estimated)
Ages18 Years and up
SexAll
SponsorBayer Industry-sponsored
Drugs / interventionstrastuzumab, pembrolizumab, poziotinib, chemotherapy, radiation, sevabertinib
Locations283 sites (Newport Beach, California and 282 other locations)
Trial IDNCT06452277 on ClinicalTrials.gov

What this trial studies

This study aims to assess the effectiveness and safety of BAY 2927088 in treating patients with advanced non-small cell lung cancer (NSCLC) that has specific mutations in the HER2 gene. Participants will receive BAY 2927088 and its performance will be compared to standard treatments such as Pembrolizumab, Cisplatin, Carboplatin, and Pemetrexed. The study focuses on patients who have not received prior systemic therapy for their advanced disease. Researchers hope to determine if blocking the mutated HER2 protein can halt the progression of NSCLC.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced non-squamous NSCLC and documented HER2 mutations.

Not a fit: Patients with small cell lung cancer or those who have previously received HER2-targeted therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced NSCLC harboring HER2 mutations.

How similar studies have performed: Other studies targeting HER2 mutations in lung cancer have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Participant must be ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signing the informed consent.
* Documented histologically or cytologically confirmed locally advanced non-squamous NSCLC, not suitable for definitive therapy or metastatic non-squamous NSCLC at screening (small cell or mixed histologies are excluded) (Stage III-IV NSCLC).
* Documented activating HER2 mutation in the tyrosine kinase domain (TKD) assessed by tissue molecular test in a CLIA-certified (US sites) or an equally accredited (outside of the US) local laboratory. However, participants may be included at the discretion of the investigator if the laboratory performing the assay is not CLIA or similar certified but the laboratory is locally accredited.
* No prior systemic therapy for locally advanced or metastatic disease. No prior treatment with a HER2 ex20ins-targeted therapy (e.g. poziotinib, trastuzumab deruxtecan). Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the start of screening.
* Eligible to receive treatment with the selected platinum-based doublet-chemotherapy (i.e. cisplatin/pemetrexed or carboplatin/pemetrexed) and pembrolizumab in accordance with the SmPC/Product Information.

Exclusion Criteria:

* Known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for five years since initiation of that therapy. Exception: the following cancer types are acceptable within five years if curatively treated or under surveillance:

  * a. in situ cancers of cervix, breast, or skin,
  * b. superficial bladder cancer (Ta, Tis and T1),
  * c. limited-stage prostate cancer,
  * d. basal or squamous cancers of the skin.
* Tumors with targetable alterations with approved available therapy, with the exception of HER2 mutation in the TKD.
* Inability to discontinue treatment with chronic systemic corticosteroids. Participants who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Replacement therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable, provided that the dose is stable for \>4 weeks prior to planned start of study intervention.
* Pre-existing peripheral neuropathy that is Grade ≥2 by CTCAE (v5.0).
* History of severe hypersensitivity reaction to treatment with a monoclonal antibody.
* Prior radiotherapy outside of the brain within 21 days before of planned start of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.

Where this trial is running

Newport Beach, California and 282 other locations

+233 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Non-small Cell Lung CancerHER2 MutationNSCLCERBB2 mutationHER2 mutation
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.