BLU-451 for Lung Cancer

No longer recruiting at 31 trial locations

Overseen By Helena Yu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Blueprint Medicines Corporation

Disqualifiers: Curative local therapy, Driver alterations, Mixed cell histology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 42

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of a new treatment, BLU-451, for people with certain types of lung cancer, including those with specific EGFR mutations. The study will test BLU-451 alone and in combination with standard chemotherapy drugs. It targets patients with advanced lung cancer who have experienced progression or have specific genetic changes in their tumors. This trial might be suitable for those who have tried other treatments without success or have specific EGFR mutations. As a Phase 1 trial, participants will be among the first to receive this new treatment, helping researchers understand its effects in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BLU-451 is generally safe for treating certain types of lung cancer. In earlier studies, patients who took BLU-451, either alone or with chemotherapy, usually tolerated it well. Some side effects occurred, but they were mostly mild to moderate, indicating that the treatment doesn't cause serious problems for most people.

The current study is a Phase 1 trial, focusing on the safety of BLU-451 and how the body processes it. In Phase 1 trials, researchers closely monitor participants to quickly address any unwanted effects. Although the treatment remains under study, early results suggest it is well-tolerated, offering hope for those with specific EGFR mutations in lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BLU-451 for lung cancer because it targets specific EGFR mutations, which are not always addressed by existing treatments like afatinib or erlotinib. Unlike traditional therapies, BLU-451 is designed to tackle Ex20ins and atypical EGFR mutations, offering hope for patients who have limited options. This targeted approach could provide a new avenue for treating patients who have not responded to standard therapies, potentially improving outcomes for those with these challenging genetic profiles.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that BLU-451 may help treat advanced non-small cell lung cancer (NSCLC) in patients with certain EGFR mutations. In early studies, some patients experienced tumor shrinkage, with a few seeing noticeable reductions. BLU-451 specifically targets EGFR exon 20 insertion mutations, which current therapies find difficult to treat. In this trial, some participants will receive BLU-451 alone, while others will receive it in combination with the chemotherapy drugs carboplatin and pemetrexed. This combination aims to improve treatment success for both common and rare EGFR mutations. Overall, these early findings suggest that BLU-451 could be a promising option for patients with these specific genetic mutations in lung cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• BLU-451
• Carboplatin
• Pemetrexed

Trial Overview

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.

How Is the Trial Designed?

Group I: Phase II - Cohort 2G Experimental Treatment 1 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 2F Experimental Treatment 1 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 2E Experimental Treatment 1 Intervention

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

Group IV: Phase II - Cohort 2D Experimental Treatment 1 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 2C Experimental Treatment 1 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 2B Experimental Treatment 1 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 2A Experimental Treatment 1 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 Enrichment Experimental Treatment 1 Intervention

BLU-451 enrichment at select doses.

Group IX: Phase I - Part 1B Dose Escalation (US only) Experimental Treatment 3 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 Escalation Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Blueprint Medicines Corporation

Lead Sponsor

Trials

31

Recruited

6,000+

Published Research Related to This Trial

This study analyzed data from the Japanese Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) to investigate the incidence of interstitial lung disease (ILD) potentially caused by antifibrotic drugs nintedanib and pirfenidone, both of which are first-line treatments for idiopathic pulmonary fibrosis (IPF).

The findings indicated that both nintedanib and pirfenidone were associated with signals for causing ILD, emphasizing the need for careful monitoring of these drugs due to their limited effectiveness and potential to induce lung damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects. Nawa, H., Hamano, H., Niimura, T., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The maximum tolerated dose (MTD) for the carboplatin and paclitaxel combination was established at 235 mg/m2 and 375 mg/m2, respectively, showing a good safety profile with minimal neutropenia and no thrombocytopenia in 50 patients with advanced non-small cell lung cancer.

The treatment resulted in an overall response rate of 38%, with a median overall survival time of 51.81 weeks and a 1-year survival rate of 49%, indicating that this combination therapy is both effective and well tolerated in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II dose finding study of paclitaxel and carboplatin in advanced non-small cell lung cancer. Scagliotti, GV., Crinó, L., Pozzi, E., et al.[2019]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

A total of 9202 adverse pulmonary events related to immune checkpoint inhibitors were identified, with common issues including pneumonitis, interstitial lung disease, and respiratory failure, indicating significant pulmonary toxicity associated with these treatments.

Most pulmonary immune-related adverse events were severe and contributed to a notable number of fatalities, suggesting that the risks of using immune checkpoint inhibitors may be underrecognized in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy. Reese, SW., Cone, E., Marchese, M., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced non-small-cell lung cancer. Raez, LE., Lilenbaum, R.[2006]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9064

Emerging phase 1 data of BLU-451 in advanced NSCLC ...

Conclusions: As of the data cutoff, BLU-451 monotherapy was generally well tolerated, with early evidence of clinical activity in heavily ...

2.

blueprintmedicines.com

blueprintmedicines.com/wp-content/uploads/2023/06/Blueprint-Medicines-ASCO-2023-BLU-451-NSCLC-EGFRexon20-Emerging-Data-Poster.pdf

Emerging phase 1 data of BLU-451 in advanced NSCLC ...

Early evidence of tumor reduction was observed in efficacy-evaluable patients (Figure 3b). Confirmed partial responses (PR) by Response ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05241873

(Concerto) Study of BLU-451 in Advanced Cancers With ...

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 ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12056541/

Efficacy and safety outcomes of emerging EGFR‑TKIs for ...

In conclusion, the emerging EGFR-TKIs for patients with NSCLC with EGFR exon 20 insertion mutations have good treatment outcome; however, the PFS outcome ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666634025002302

Review Current paradigm of EGFR ins20 in non-small cell ...

Early results from this study indicated that untreated NSCLC patients with EGFRins20 mutations demonstrated a promising overall response rate of ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S1556086422010413

EP08.02-018 Phase 1/2 Study of BLU-451, a Small ...

BLU-451-1101 (NCT05241873) is a phase 1/2, global, open-label study designed to evaluate single-agent BLU-451 in patients with NSCLC harboring EGFR ex20ins ...