(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC
- Trial number:
- NCT04862780
- Trial phase:
- 1, 2
- Study type:
- Targeted therapy
- Overall status:
- Recruiting
Study start date
Scientific title
Summary
≥18 years of age at the time of signing the informed consent.Pathologically confirmed, definitively diagnosed, metastatic NSCLC harboring an activating EGFR mutation.
Previously received at least 1 prior EGFR-targeted TKI with activity against the T790M mutation, such as osimertinib.
a. Phase 1 Part 1B and Phase 2 Group 4: Patients must have experienced progressive disease while on osimertinib, and were able to tolerate prior osimertinib 80 mg QD dose.
Tumor mutation profile determined locally via a Sponsor-approved testing methodology, using tumor tissue (ideally from a progressing lesion) and/or ctDNA in plasma. For Phase 1, it is preferable that samples used for analysis be obtained during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pre-treatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI received.
Dose Escalation (Phase 1 Part 1A and Part 1B): At each dose level, slots may be reserved for patients with the mutations of interest.BLU-945 Monotherapy Expansion Groups (Phase 2 Group 1, Group 2, and Group 3): Patients must have NSCLC harboring EGFR T790M and C797S mutation (Group 1); EGFR T790M but not C797S (Group 2); or EGFR C797S but not T790M (Group 3). BLU-945 with Osimertinib Expansion (Phase 2 Group 4): Slots may be reserved for patients with mutations of interest, but at least 12 slots will be allocated to patients with NSCLC harboring EGFR T790M and C797S mutation.
Pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy) submitted for central analysis. For Phase 1, it is preferable that pretreatment tumor samples be obtained from a progression lesion, during or after disease progression on the last EGFR-targeted TKI received. For Phase 2, pre-treatment tumor sample must be obtained during or after disease progression on the last EGFR-targeted TKI received.
Patients without appropriate archival tissue available, where biopsy is not considered safe and/or medically feasible, may be discussed with the study medical monitor and may be approved for enrollment on a case-by-case basis.
Phase 2 Expansion Groups: Patient has at least 1 measurable target lesion evaluable by RECIST 1.1 as assessed by the investigator.Eastern Cooperative Oncology Group (ECOG) performance status is 0-1. Agrees to use contraception consistent with the protocol and local regulations