What side effects are associated with this type of intervention?

Common treatments for lung cancer, such as chemotherapy and immunotherapy, have a range of side effects. Chemotherapy, including platinum-based agents like carboplatin and pemetrexed, often causes nausea, vomiting, fatigue, hair loss, and increased risk of infections due to lowered blood cell counts. Immunotherapy agents, such as pembrolizumab and atezolizumab, can lead to immune-related side effects like pneumonitis, colitis, hepatitis, and endocrinopathies. Investigational agents like BLU-451, while still under study, may have side effects similar to other targeted therapies, including gastrointestinal disturbances, fatigue, and potential liver enzyme abnormalities. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

Several FDA-approved treatments for lung cancer target specific genetic mutations or pathways. For instance, osimertinib is approved for non-small cell lung cancer (NSCLC) with EGFR mutations, including exon 20 insertions. ALK inhibitors like alectinib and crizotinib are approved for ALK-positive NSCLC. Immunotherapies such as pembrolizumab and atezolizumab, which target PD-1/PD-L1, have shown efficacy in improving overall survival and progression-free survival in various subtypes of NSCLC. These treatments highlight the trend towards personalized medicine in lung cancer, focusing on specific molecular targets similar to the investigational agent BLU-451.

What other types of research exist?

Promising novel alternatives to BLU-451 for lung cancer patients in 2024 include: 1) Immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1/PD-L1 pathways. 2) Tyrosine kinase inhibitors (TKIs) like osimertinib for EGFR mutations. 3) Combination therapies involving platinum-based chemotherapy with agents like carboplatin and pemetrexed. 4) Investigational agents such as regorafenib and cabozantinib, which target multiple kinases. These options have shown efficacy in clinical trials and may provide viable alternatives for lung cancer treatment.

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Small Molecule Inhibitor

BLU-451 for Lung Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Blueprint Medicines Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed metastatic NSCLC stage IVA & IVB per AJCC 8th Edition (Phase 1 and Phase 2) or other metastatic cancers except for primary CNS tumors (Phase 1 only).

Documented EGFR Ex20ins based on NGS testing of tumor or liquid biopsy.

Must not have

Disease that is suitable for local therapy administered with curative intent

NSCLC with mixed cell histology or a tumor with known histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12-15 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

The 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.

What are the potential side effects?

While specific side effects of BLU-451 are not listed here, common ones from similar treatments include nausea, fatigue, blood count changes leading to increased infection risk or bleeding problems; liver or kidney function changes; allergic reactions; and potential nerve damage.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is confirmed to be advanced non-small cell lung cancer or another type of metastatic cancer, excluding brain tumors.

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My cancer has a specific EGFR mutation detected by a special test.

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I am undergoing or need platinum-based chemotherapy, unless it's not suitable for me.

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My cancer has spread, is measurable, and didn't respond to my last treatment.

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My lung cancer is confirmed to be at an advanced stage with measurable signs.

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My cancer has an EGFR mutation confirmed by a certified test.

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I am fully active or can carry out light work.

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I haven't had seizures for at least 14 days and my anti-epileptic drug doses have been stable for the same period.

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My cancer has spread, is measurable, and didn't respond to my last treatment.

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My lung cancer is at an advanced stage and can be measured for changes.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My lung cancer has changed its cell type.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12-15 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12-15 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12-15 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase I - Determine the Recommended Phase 2 Dose (RP2D) of BLU-451

Phase I - Determine the maximum tolerated dose (MTD) of BLU-451

Heart rate

Secondary study objectives

Phase I & II - The Clinical Benefit Rate (CBR) of BLU-451

Phase I & II - The Disease Control Rate (DCR) rate of BLU-451

Phase I & II - The Duration of Response (DOR) rate of BLU-451

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pemetrexed

2014

Completed Phase 3

~5550

Carboplatin

2014

Completed Phase 3

~6120

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for lung cancer include EGFR inhibitors, ALK inhibitors, and immune checkpoint inhibitors. EGFR inhibitors, such as tyrosine kinase inhibitors (TKIs), block the epidermal growth factor receptor, which is often mutated in lung cancer, thereby inhibiting cancer cell growth and survival. ALK inhibitors target the anaplastic lymphoma kinase gene rearrangements, which drive tumor growth in a subset of lung cancer patients. Immune checkpoint inhibitors, like anti-PD-1 and anti-PD-L1 therapies, enhance the immune system's ability to recognize and destroy cancer cells by blocking proteins that suppress immune responses. These mechanisms are crucial for lung cancer patients as they offer targeted and effective treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy. Investigational agents like BLU-451 are being studied to further expand these targeted therapies, offering hope for more personalized and effective treatments.

Efficacy and Safety of EGFR Tyrosine Kinase Inhibitors Combined with Cranial Radiotherapy for Brain Metastases from Non-Small-Cell Lung Cancer: A Protocol for a Systematic Review and Meta-Analysis.Toxicity of radiation and immunotherapy combinations.Effect of ALK-inhibitors in the treatment of non-small cell lung cancer: a systematic review and meta-analysis.