BLU-451 for Lung Cancer

Recruiting in Palo Alto (17 mi)

+25 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Blueprint Medicines Corporation

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BLU-451, alone and with chemotherapy, in patients with advanced cancers that have specific EGFR mutations. The drug works by blocking signals that make cancer cells grow.

Research Team

Eligibility Criteria

Adults (18+) with advanced cancers that have a specific mutation called EGFR Exon 20 insertion, based on testing. They should not have seizures and must be generally healthy with good organ function. The trial is open to those who've progressed after systemic therapy or can't tolerate it, except for primary brain tumors.

Inclusion Criteria

I am fully active or can carry out light work.

I can provide a tumor sample from before my treatment.

I may have been treated with specific lung cancer drugs but it's not mandatory.

See 15 more

Exclusion Criteria

My tumor has a specific genetic change known to drive cancer growth.

My lung cancer has changed its cell type.

My condition can be treated with the goal of curing it.

Treatment Details

Interventions

BLU-451 (Small Molecule Inhibitor)
Carboplatin (Chemotherapy)
Pemetrexed (Chemotherapy)

Trial OverviewThe study tests BLU-451 alone and combined with chemotherapy drugs carboplatin and pemetrexed in patients with certain mutations in their cancer cells. Participants will receive treatment every 21 days to evaluate safety, how the body processes the drug, its effects on tumors, and overall anti-cancer activity.

Participant Groups

10Treatment groups

Experimental Treatment

Group I: Phase II - Cohort 2GExperimental Treatment1 Intervention

Participants with EGFR atypical mutations (e.g., G719X, L861Q) who have not received prior systemic therapy in metastatic setting will receive BLU-451. Participants with with other atypical EGFR mutations, such as S768I, may be enrolled if approved by Sponsor Medical Monitor.

Group II: Phase II - Cohort 2FExperimental Treatment1 Intervention

Participants with EGFR atypical mutations (e.g., G719X, L861Q) who have previously received at least one EGFR tyrosine kinase inhibitor (TKI) will receive BLU-451. Participants with with other atypical EGFR mutations, such as S768I, may be enrolled if approved by Sponsor Medical Monitor.

Group III: Phase II - Cohort 2EExperimental Treatment1 Intervention

Participants with EGFR Ex20ins who have not received prior systemic therapy in metastatic setting will receive BLU-451.

Group IV: Phase II - Cohort 2DExperimental Treatment1 Intervention

Participants with EGFR Ex20ins who have previously received platinum-based chemotherapy and both amivantamab AND mobocertinib, OR received any investigational Ex20Ins targeted agent(s) will receive BLU-451. Participants with Ex20ins or atypical mutations enrolled in other cohorts and who have other oncogenic drivers by central testing at baseline will be moved to this arm.

Group V: Phase II - Cohort 2CExperimental Treatment1 Intervention

EGFR Ex20ins participants with at least one measurable lesion in brain per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 who have previously received platinum-based chemotherapy will receive BLU-451. Previous treatment with EGFR Ex20Ins-targeted therapies is allowed but not required.

Group VI: Phase II - Cohort 2BExperimental Treatment1 Intervention

EGFR Ex20ins participants who have previously received platinum-based chemotherapy but have not received a prior EGFR Ex20ins-targeted agent will receive BLU-451.

Group VII: Phase II - Cohort 2AExperimental Treatment1 Intervention

EGFR Ex20ins participants who have previously received platinum-based chemotherapy and either amivantamab or mobocertinib will receive BLU-451.

Group VIII: Phase I - Part 2 BLU-451 Monotherapy EnrichmentExperimental Treatment1 Intervention

BLU-451 enrichment at select doses.

Group IX: Phase I - Part 1B Dose Escalation (US only)Experimental Treatment3 Interventions

BLU-451 with dose escalation in combination with carboplatin and pemetrexed in participants with metastatic NSCLC with common EGFR mutations. This arm will enroll participants only in the United States.

Group X: Phase I - Part 1A Dose EscalationExperimental Treatment1 Intervention

BLU-451 monotherapy with dose escalation in participants with metastatic cancer with EGFR Ex20ins or other selected EGFR mutations that have progressed after prior systemic therapies.