What side effects are associated with this type of intervention?

Common treatments for Neurofibromatosis, particularly those involving EGFR inhibitors like erlotinib, gefitinib, and lapatinib, often result in cutaneous adverse events. The most frequently reported side effects include xerosis (dry skin), papulo-pustular eruptions, and erythematous maculopapular rashes. These skin toxicities are significant but manageable with appropriate preventive and therapeutic strategies.

What prior FDA approvals exist?

Currently, there are no FDA-approved treatments specifically targeting EGFR for Neurofibromatosis. However, lapatinib, an EGFR and HER2 inhibitor, has shown potential growth-inhibitory effects on meningiomas in Neurofibromatosis type 2 (NF2) patients. This suggests that targeted therapies, like BLU-945, which is a selective EGFR inhibitor, may hold promise for future treatment options in Neurofibromatosis.

What other types of research exist?

Promising alternatives to BLU-945 for Neurofibromatosis patients include: 1) Dabrafenib plus Trametinib, which targets BRAF V600E mutations and has shown efficacy in various tumor types, including gliomas. 2) Selumetinib, a MEK inhibitor, which is being evaluated in ongoing trials for low-grade gliomas in patients with and without NF1. 3) Bevacizumab, an angiogenesis inhibitor, which has shown qualitative improvement in vision for patients with optic pathway gliomas. These treatments target relevant pathways and have shown potential in clinical studies.

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EGFR Inhibitor

Osimertinib + BLU-945 for Non-Small Cell 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

≥18 years of age at the time of signing the informed consent.

Previously received at least 1 prior EGFR-targeted TKI with activity against the T790M mutation, such as osimertinib

Must not have

Major surgical procedure within 14 days of the first dose of study drug

Clinically significant, uncontrolled, cardiovascular disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 42 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing BLU-945, a new drug that targets cancer proteins, alone or with osimertinib. It focuses on patients with specific EGFR gene mutations. The drug aims to block a protein that helps cancer cells grow.

Who is the study for?

Adults with metastatic non-small cell lung cancer (NSCLC) that has specific mutations in the EGFR gene. They must have previously been treated with an EGFR-targeted therapy like osimertinib and shown disease progression on it. Participants need to be generally healthy, with a good performance status, and able to use contraception.

What is being tested?

The trial is testing BLU-945 alone or combined with osimertinib for safety, tolerability, how the body processes it, its effects on the body, and its ability to fight cancer in patients whose NSCLC has certain EGFR mutations resistant to previous treatments.

What are the potential side effects?

Potential side effects include typical reactions related to targeted cancer therapies such as skin rash, diarrhea, dry skin, nail changes; however detailed side effect profiles will be determined during this early phase of testing.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I have been treated with a drug targeting EGFR mutation before.

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My lung cancer is advanced and has a specific EGFR gene change.

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I am fully active or can carry out light work.

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My cancer's genetic changes were tested with approved methods.

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My NSCLC has specific EGFR mutations.

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I am 18 years old or older.

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I have been treated with a specific lung cancer medication before.

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My cancer progressed on osimertinib, but I tolerated the 80 mg daily dose well.

Exclusion Criteria

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

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I have not had major surgery within the last 2 weeks.

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I have a serious heart condition that is not under control.

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I don't have lasting side effects from previous treatments above mild level.

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I have a heart condition that affects my heart's electrical activity.

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I do not have any active, uncontrolled infections or known COVID-19.

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I have a known bleeding disorder or brain bleed.

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My cancer has spread to my brain or spine, causing worsening symptoms or needing more steroids.

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My lung cancer is of mixed type or has changed its cell type.

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My tumor has other known genetic changes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 42 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 42 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 42 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 1] Determine recommended Phase 2 dose (RP2D) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib

[Phase 1] Determine the maximum tolerated dose (MTD) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib

[Phase 2] Overall response rate (ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib

Secondary study objectives

[Phase 1 and Phase 2] Assess treatment-induced modulation of EGFR pathway biomarkers.

[Phase 1 and Phase 2] Duration of response (DOR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib

[Phase 1] Overall response rate (ORR) of BLU-945 as monotherapy and BLU-945 in combination with osimertinib

+8 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

6Treatment groups

Experimental Treatment

Group I: Phase 2, Group 4: BLU-945 with osimertinibExperimental Treatment2 Interventions

Phase 2 expansion group for BLU-945 with osimertinib at a dose determined during Part 1B in patients

Group II: Phase 2, Group 3: BLU-945 as monotherapyExperimental Treatment1 Intervention

Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR C797S mutations

Group III: Phase 2, Group 2: BLU-945 as monotherapyExperimental Treatment1 Intervention

Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M mutations

Group IV: Phase 2, Group 1: BLU-945 as monotherapyExperimental Treatment1 Intervention

Phase 2 expansion group for BLU-945 as monotherapy at a dose determined during Part 1A in patients with EGFR T790M and C797S mutations

Group V: Part 1B: BLU-945 with osimertinibExperimental Treatment2 Interventions

Phase 1 dose escalation of BLU-945 in combination with osimertinib 80 mg tablets for oral administration

Group VI: Part 1A: BLU-945 as monotherapyExperimental Treatment1 Intervention

Phase 1 dose escalation of BLU-945 as monotherapy at various dose levels

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

osimertinib

2023

Completed Phase 2

~160

0 / 18Eligibility 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 Neurofibromatosis type 2 (NF2) include targeted therapies such as bevacizumab, which inhibits VEGF to reduce tumor blood supply, and everolimus, which disrupts mTORC1 pathways to inhibit cell growth. Lapatinib, an EGFR/ErbB2 inhibitor, targets the EGFR family to reduce tumor cell survival and proliferation. These treatments are important for NF2 patients as they offer targeted approaches to manage tumor growth and symptoms, potentially improving quality of life and reducing the need for surgery.

Summary statement novel agents in the treatment of lung cancer: Fifth Cambridge Conference assessing opportunities for combination therapy.Targeted molecular therapies against epidermal growth factor receptor: past experiences and challenges.ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma.