103 Participants Needed

BLU-451 for Lung Cancer

Recruiting at 25 trial locations
BM
Helena A. Yu, MD - MSK Thoracic Medical ...
Overseen ByHelena Yu, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Blueprint Medicines Corporation
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on anti-epileptic drugs, you must be on a stable dose for at least 14 days before joining the trial.

What data supports the effectiveness of the drug BLU-451 for lung cancer?

Research indicates that platinum-based combination chemotherapy, like those involving Carboplatin, can modestly increase survival time and improve symptoms in patients with non-small cell lung cancer. Additionally, combination chemotherapy is the standard of care for advanced cases, suggesting potential benefits when used with other drugs like BLU-451.12345

What safety data exists for BLU-451 and related treatments for lung cancer?

The safety of targeted therapies for lung cancer, like BLU-451, includes potential side effects such as skin issues, stomach problems, lung issues, and heart problems. It's important to monitor these side effects regularly during treatment.678910

What makes the drug BLU-451 unique for treating lung cancer?

The research provided does not contain specific information about BLU-451, so I cannot determine what makes it unique compared to existing treatments for lung cancer.1112131415

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Initial dose-escalation to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-451, including combination with carboplatin and pemetrexed

12-15 months
21-day treatment cycles

Phase 2 Treatment

Evaluation of efficacy and safety of BLU-451 as monotherapy at RP2D in participants with NSCLC

12-15 months
21-day treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • BLU-451
  • Carboplatin
  • Pemetrexed
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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Blueprint Medicines Corporation

Lead Sponsor

Trials
31
Recruited
6,000+

Findings from Research

Chemotherapy, particularly platinum-based doublets, has been shown to prolong survival and enhance quality of life in patients with advanced non-small-cell lung cancer, especially those with a good performance status.
The introduction of newer agents with different mechanisms of action is paving the way for improved treatment outcomes, indicating a shift in management strategies for this type of lung cancer.
Chemotherapy for advanced non-small-cell lung cancer.Raez, LE., Lilenbaum, R.[2006]
Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.
The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.
Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer.Hines, JB., Bowar, B., Levine, E., et al.[2023]
In a study of 16,527 non-small cell lung cancer patients, the most common adverse events linked to pharmacotherapy were hypocalcemia, elevated creatine phosphokinase, and hypertriglyceridemia, highlighting the need for monitoring these conditions during treatment.
The modified Apriori algorithm proved to be more effective than the conventional method in identifying associations between chemotherapy drugs and adverse events, suggesting it could be a valuable tool for improving patient safety in cancer pharmacotherapy.
Discovering Associations of Adverse Events with Pharmacotherapy in Patients with Non-Small Cell Lung Cancer Using Modified Apriori Algorithm.Chen, W., Yang, J., Wang, HL., et al.[2022]

References

Future directions in the treatment of non-small cell lung cancer. [2005]
Treatment of metastatic non-small cell lung cancer. [2022]
Adjuvant Chemotherapy. [2020]
Advances in cytotoxic chemotherapy for the treatment of metastatic or recurrent non-small cell lung cancer. [2019]
Chemotherapy for advanced non-small-cell lung cancer. [2006]
Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. [2023]
Age-related differences in patient-reported outcomes in patients with advanced lung cancer receiving anti-PD-1/PD-L1 therapy. [2019]
Discovering Associations of Adverse Events with Pharmacotherapy in Patients with Non-Small Cell Lung Cancer Using Modified Apriori Algorithm. [2022]
Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy. [2021]
Phase I/II dose finding study of paclitaxel and carboplatin in advanced non-small cell lung cancer. [2019]
[Chemotherapy for metastatic non-small cell lung cancer]. [2006]
The Position of Inhaled Chemotherapy in the Care of Patients with Lung Tumors: Clinical Feasibility and Indications According to Recent Pharmaceutical Progresses. [2020]
14.United Statespubmed.ncbi.nlm.nih.gov
Triplet combination chemotherapy and targeted therapy regimens. [2005]
15.United Statespubmed.ncbi.nlm.nih.gov
Phase I-II trial of concomitant continuous carboplatin (CBDCA) infusion and radiotherapy in advanced nonsmall cell lung cancer with evaluation for surgery: final report. [2019]