Clinical Trials

Phase 2 Eligibility:
Key Inclusion Criteria Required for locally advanced or metastatic NSCLC:
* Measurable disease by RECIST 1.1 criteria.
* Adequate bone marrow or organ function.
* Life expectancy of ≥ 3 months.
* Sufficient performance status.
* Confirmed NSCLC, without small cell lung cancer transformation with or without brain metastases.
* Disease progression following or intolerance of standard of care (excluding patients in the treatment-naïve non-classical driver cohort):

* Cohort 1 (Non-Classical driver cohort): Advanced/metastatic NSCLC with a non-classical driver EGFR mutation (eg, G719X) following up to 2 lines of therapy with only 1 prior EGFR TKI regimen (third-generation preferred; other approved EGFR TKI acceptable).
* Cohort 2 (Acquired resistance C797S cohort): Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only one EGFR TKI, which must be a third generation EGFR TKI (eg, osimertinib).
* Cohort 3 (First-line non-classical driver cohort): Treatment-naïve advanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle of chemotherapy or immune checkpoint inhibitor are permitted).
* Identification of one (or more) of the following EGFR mutations by Next Generation Sequencing (NGS) as determined by a local assay performed in a validated laboratory in the absence of other known resistance mutations (eg, T790M, MET):

* Non-classical driver EGFR mutations (eg, L861R, S768I, G719X).
* EGFR acquired resistance mutation (eg, C797S) to a 3rd generation EGFR TKI.
* NGS test must be obtained after progression on the most recent therapy; at the time of diagnosis for the patients in Cohort 3 only.

Key Exclusion Criteria:
* Known resistant mutations in tumor tissue or by liquid biopsy (eg, T790M, MET).
* Received more than 1 EGFR TKI therapy (ie, erlotinib or gefitinib) for the treatment of metastatic or recurrent EGFR NSCLC.
* Any history of interstitial lung disease related to EGFR TKI use.
* Symptomatic or radiographic leptomeningeal disease.
* Symptomatic brain metastases or spinal cord compression requiring urgent clinical intervention.
* Unresolved toxicity from prior therapy.
* Significant cardiovascular disease.
* Major surgery within 4 weeks of study entry or planned during study.
* Ongoing or recent anticancer therapy or radiation therapy.
* Evidence of malignancy (other than study-specific malignancies) requiring active therapy within the next 2 years.
* Active hepatitis B or C infection and/or known human immunodeficiency virus (HIV) carrier.
* Poorly controlled gastrointestinal disorders.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/01/2024. Questions regarding updates should be directed to the study team contact.