(Concerto) Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations

Phase I/II Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations

This is a Phase 1/2, open-label first-in-human study of the safety, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of BLU-451 monotherapy and BLU-451 in combination with platinum-based chemotherapy (carboplatin and pemetrexed). All participants will receive BLU-451 on a 21-day treatment cycle.

The study is a Phase 1/2 Study of BLU-451 in Advanced Cancers with Epidermal growth factor receptor (EGFR) Exon 20 Insertion Mutations (Ex20ins). The study has two phases:

An initial Phase 1 portion will enroll participants with metastatic cancer with EGFR Ex20ins or other selected EGFR mutations that have progressed after prior systemic therapies and will determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-451.

Part 1B dose-escalation will enroll participants with metastatic Non-small Cell Lung Cancer (NSCLC) in the USA only to determine the MTD and/or RP2D of BLU-451 in combination with carboplatin and pemetrexed.

A Phase 2 portion will further evaluate the efficacy and safety of BLU-451 as monotherapy at RP2D in participants with NSCLC.

INCLUSION CRITERIA:

All participants:

• Documented EGFR mutation, based on Next-generation sequencing (NGS) testing of tumor or liquid biopsy analyzed in a local Clinical Laboratory Improvement Amendments (CLIA) (or International Organization for Standardization (ISO) 15189)-certified or equivalent laboratory are required. Redacted copies of laboratory results must be available for Sponsor review.
• Able to provide a new or archived pretreatment formalin-fixed, paraffin-embedded (FFPE) tumor sample. For participants who received EGFR-targeted therapy subsequent to the most recent archived biopsy, all efforts should be made to obtain a new biopsy unless it is not safe or feasible to obtain one.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Participants must be without seizures for at least 14 days prior to enrollment, and patients who receive treatment with anti-epileptic drugs must be on stable doses for at least 14 days prior to enrollment.
• Adequate hematological, renal, and hepatic function:

Participants in Phase 1

• Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per American Joint Committee on Cancer (AJCC) 8th edition) or other metastatic cancers except for primary CNS tumors (Part 1A or Part 2 only).
• Must have evaluable or measurable disease per RECIST v1.1.
• Progression on or after or intolerance to most recent systemic therapy.

Participants in Phase 2

• Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per AJCC 8th edition).
• Must have measurable disease by RECIST 1.1.

EXCLUSION CRITERIA:

• Have disease that is suitable for local therapy administered with curative intent.
• Have tumor that harbors known driver alterations (including, but not limited to ROS, BRAF V600E, ALK, RET, HER2, MET, KRAS, NTRK1/2/3, EGFR C797X, or EGFR T790M mutation). These criteria are not applicable to Phase 1 Part 1B.
• Have NSCLC with mixed cell histology or a tumor with known histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).

Other protocol-defined inclusion and exclusion criteria apply