A Phase 3 study of BAY 2927088 compared to standard treatment in advanced non-small cell lung cancer (NSCLC) with HER2 mutations. Study 22615 ("SOHO-02").

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Singapore, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (T�rkiye), Ukraine, United Kingdom, United States (ICTRP)

ICTRP Trial ID
NCT06452277 (ICTRP)

Official title (approved by ethics committee)
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. (BASEC)

Academic title
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 (ICTRP)

Public title
A Study to Learn More About How Well Sevabertinib (BAY 2927088) Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2) (ICTRP)

Disease under investigation
Advanced Non-small Cell Lung CancerHER2 Mutation (ICTRP)

Intervention under investigation
Drug: BAY2927088Drug: PembrolizumabDrug: CisplatinDrug: CarboplatinDrug: Pemetrexed (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

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. (ICTRP)

not available

Primary and secondary end points
Progression free survival (PFS) per RECIST 1.1 as assessed by BICR (ICTRP)

Overall survival (OS);Objective response rate (ORR) per RECIST 1.1 as assessed by BICR;Progression free survival (PFS) per RECIST 1.1 as assessed by the investigator;Objective Response Rate (ORR) per RECIST 1.1 as assessed by the investigator;Disease control rate (DCR) per RECIST 1.1 as assessed by BICR;Disease control rate (DCR) per RECIST 1.1 as assessed by the investigator;Duration of response (DOR) as assessed by BICR;Duration of response (DOR) as assessed by the investigator;Adverse events per CTCAE v 5.0 (eg. TEAEs, TESAEs) categorized by severity;Change from baseline in NSCLC-SAQ total score;Change from baseline in NSCLC-SAQ individual domain scores;Time to deterioration in NSCLC-SAQ total score;Time to deterioration in NSCLC-SAQ individual domain scores;Time to deterioration in EORTC QLQ-C30 physical functioning domain score;Change from baseline in EORTC QLQ-C30 physical functioning domain score;Change from baseline in EORTC QLQ-C30 global health status/QoL (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Bayer Clinical Trials Contact, clinical-trials-contact@bayer.com, (+)1-888-84 22937 (ICTRP)

Secondary trial IDs
2024-511319-91-00, 22615 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/study/NCT06452277 (ICTRP)