longkanker lung cancer non-small cell lung cancer (NSCLC)
Conditions
Interventions
BAY 2927088 will be administered in 21-day cycles with continual daily oral
administration and no treatment pause between cycles. Alternative dosing
schedules may be explored.
Sponsors
Bayer
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Key General Inclusion Criteria 2. Documented histologically or cytologically confirmed locally advanced NSCLC, not suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small cell or mixed histologies are excluded). 3. Documented disease progression after treatment with at least one prior systemic therapy for advanced disease. Participants who do not have standard of care access due to any reason, are intolerant to, or are not eligible for standard treatments, may also be eligible. Participants previously treated with systemic therapy who are known to have acquired an actionable resistance alteration in a gene other than EGFR/HER2 should first be treated with available approved therapy that targets the identified gene alteration prior to enrolling to this study 4. Adequate archival tumor tissue (ideally taken after last targeted treatment and not older than 6 months) has to be available, either from primary or metastatic sites. If archival material is not available, a fresh tumor biopsy should be performed if feasible and if the procedure poses no significant risk for the participant. 5. Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsyduring the screening period (if a biopsy is taken during screening) that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied lesion should not be used as a target lesion for RECIST 1.1 tumor assessments. Previously irradiated lesions must have shown progression to be considered measurable. 6. Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (United States [US] sites) or an equally accredited (outside of the US) local laboratory. However, participantsmay be included after discussion with the Sponsor if the laboratory performing the assay is not CLIA or similar certified. 8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Key Inclusion Criteria specific to Dose Expansion 301. Expansion Group A: NSCLC participants with EGFR ex20ins mutation and naïve to EGFR ex20ins-targeted therapy (e.g., mobocertinib, CLN-081, amivantamab, poziotinib). Participants who had prior treatment with EGFR ex20ins-targeted therapy for <= 2 months and stopped treatment due to reasons other than progressive disease are also eligible. 401. Expansion Group B1: NSCLC participants with EGFR ex20ins mutation previously treated with EGFR ex20ins-targeted bispecific antibodies (e.g. amivantamab). Prior treatment with EGFR ex20ins-TKIs is exclusionary unless treatment lasted for <= 2 months and was stopped due to reasons other than progressive disease. 402. Expansion Group B2: NSCLC participants with EGFR ex20ins mutation treated with no more than one prior EGFR ex20ins-TKI (e.g mobocertinib, CLN-081, poziotinib). 501. Expansion Group C: NSCLC participants with a secondary EGFR resistance mutation C797X and naïve to EGFR C797X-targeted TKI therapy. Participants who had prior treatment with EGFR C797X -targeted TKIs for <= 2 months and stopped treatment due to reasons other than progressive disease are also eligible. 601. Expansion Group D: NSCLC participants with HER2 activating mutations (in
Exclusion criteria
Exclusion criteria: Key General Exclusion Criteria: 6. Have any unresolved toxicity of Grade >= 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor. 7. Any history of primary brain or leptomeningeal disease (symptomatic or asymptomatic), presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local treatment (such as radiotherapy or surgery). 8. History of spinal cord compression or brain metastases with the following exceptions: a. Participants with treated brain metastases that are asymptomatic at screening and who are off or receiving low-dose of corticosteroids (3 months from definitive therapy and stable by imaging (MRI or CT) during the screening period and clinically asymptomatic Key Exclusion Criteria specific to Backfill and Expansion cohorts: 101. History or presence of the EGFR T790M mutation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity. Number of participants who discontinue study treatment due to an AE - MTD or MAD of BAY 2927088 within the DLT observation period in Dose Escalation (including participants from Backfill) - Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY 2927088 in the DLT observation period in Dose Escalation (including participants from Backfill) - PK parameters: Cmax and area under the curve (AUC) of the respective dosing interval of BAY 2927088 after single dose and multiple dose administrations | — |
Secondary
| Measure | Time frame |
|---|---|
| - Overall response rate (ORR) as per RECIST v1.1 by Investigator assessment - Safety/tolerability endpoints as described under Primary endpoints, PK as described under Primary endpoints, and ORR per RECIST as assessed by INV from BAY 2927088 dose(s) evaluated in Dose Escalation, Backfill and Dose Expansion parts | — |
Countries
Netherlands
Outcome results
None listed