BG-60366 for Non-Small Cell Lung Cancer

Recruiting at 39 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: BeiGene

Must not be taking: Fourth-gen EGFR-TKI, PROTACs

Disqualifiers: Small cell disease, Brain metastases, ILD, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is an open-label, multicenter, Phase 1a/1b clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BG-60366, a highly potent, selective EGFR-mutation targeted Chimeric Degradation Activation Compound (CDAC). BG-60366 is designed to degrade mutant EGFR, which is a common cause for Non-Small Cell Lung Cancer (NSCLC). This study will evaluate how well BG-60366 works in participants with advanced or metastatic EGFR-mutant NSCLC. The study will be conducted in 2 parts: 1) Phase 1a Dose Escalation and Safety Expansion, and 2) Phase 1b Dose Expansion.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does exclude those who have been treated with certain EGFR-targeting drugs, so you may need to discuss your current medications with the trial team.

What data supports the effectiveness of the drug BG-60366 for non-small cell lung cancer?

Research shows that adding bevacizumab, a drug similar to BG-60366, to chemotherapy improved survival in non-small cell lung cancer patients, extending their lives beyond one year. This suggests that BG-60366, if similar in action, might also be effective in treating this type of cancer. ^{1 2 3 4 5}

What safety data exists for BG-60366 in humans?

In a Phase II trial, MGBG (another name for BG-60366) was given to patients with non-small cell lung cancer and was found to be reasonably well-tolerated, meaning it did not cause severe side effects at the tested dose. ^{1 5 6 7 8}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific mutation in the EGFR gene. Participants must have progressed after treatment with an EGFR-tyrosine kinase inhibitor and be ineligible for or have progressed on standard treatments like platinum-based chemotherapy. They should have at least one measurable tumor lesion and a stable physical status.

Inclusion Criteria

I have at least one tumor that can be measured or evaluated.

My EGFR mutation was found in a recent test after my last cancer treatment.

My organs are working well.

Exclusion Criteria

I haven't taken specific advanced drugs for EGFR mutation in my cancer.

I have brain metastases needing urgent treatment.

I frequently need drainage for fluid build-up in my chest or abdomen.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a: Dose Escalation and Safety Expansion

Sequential cohorts of increasing dose levels of BG-60366 will be evaluated as monotherapy

Approximately 18 months

Phase 1b: Dose Expansion

Recommended Dose(s) for Expansion (RDFE[s]) of BG-60366 as monotherapy determined from Phase 1a will be evaluated

Approximately 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BG-60366 (Chimeric Degradation Activation Compound)

Trial Overview The study tests BG-60366, a new drug targeting mutant EGFR to treat NSCLC. It's an open-label trial with two parts: Phase 1a explores safe dosage levels and expands safety data, while Phase 1b focuses on confirming the dose's effectiveness against tumors.

Participant Groups

Group I: Phase 1b: Dose Expansion Experimental Treatment 1 Intervention

Recommended Dose(s) for Expansion (RDFE\[s\]) of BG-60366 as monotherapy determined from Phase 1a will be evaluated.

Group II: Phase 1a: Dose Escalation and Safety Expansion Experimental Treatment 1 Intervention

Sequential cohorts of increasing dose levels of BG-60366 will be evaluated as monotherapy.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

The addition of bevacizumab, a monoclonal antibody targeting VEGF, to standard chemotherapy (paclitaxel and carboplatin) has been shown to provide a survival advantage for patients with advanced non-squamous non-small-cell lung cancer, extending survival beyond 1 year for the first time.

This study, ECOG-E4599, highlights the potential of combining biological agents with traditional chemotherapy to enhance treatment efficacy, marking a significant advancement in lung cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and non-small-cell lung cancer: starving the enemy to survive. Grossi, F., Aita, M.[2019]

Three molecularly targeted agents have been identified to improve overall survival in advanced non-small cell lung cancer (NSCLC), including erlotinib, bevacizumab, and cetuximab, highlighting a shift from traditional chemotherapy to targeted therapies.

Erlotinib and bevacizumab have received FDA approval, with bevacizumab showing a median survival benefit of 1 year when combined with first-line chemotherapy, indicating a significant advancement in treatment options for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of patients with advanced non-small cell lung cancer: current and emerging options. Triano, LR., Deshpande, H., Gettinger, SN.[2022]

In a study of 840 patients with completely resected non-small-cell lung cancer (NSCLC), adjuvant chemotherapy with vinorelbine plus cisplatin significantly improved overall survival compared to observation, with a median survival of 65.7 months versus 43.7 months.

The chemotherapy group showed an 8.6% improvement in 5-year survival rates, indicating that adjuvant chemotherapy can be an effective treatment option for enhancing survival in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Douillard, JY., Rosell, R., De Lena, M., et al.[2022]

Erlotinib, an EGFR tyrosine kinase inhibitor, showed a modest 2-month improvement in overall survival for previously treated non-small-cell lung cancer (NSCLC) patients compared to placebo, highlighting its efficacy in advanced disease.

The combination of chemotherapy with bevacizumab demonstrated superior overall survival or progression-free survival in advanced non-squamous NSCLC, indicating that targeted therapies can enhance treatment outcomes, but further innovative strategies are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging drugs for non-small-cell lung cancer. Felip, E., Santarpia, M., Rosell, R.[2019]

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]

In a Phase II trial involving 108 patients with non-small cell lung cancer, MGBG was administered at a dose of 600 mg/m2 weekly, showing partial responses in only 4 out of 83 patients with adenocarcinoma and squamous cell carcinoma.

Overall, MGBG was reasonably well-tolerated, but the study concluded that it has no substantial antitumor activity for patients with non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II evaluation of MGBG in non-small cell carcinoma of the lung. A Southwest Oncology Group study. Vance, RB., Knight, WA., Chen, TT., et al.[2019]

In a phase II trial involving 51 patients with non-small cell lung cancer (NSCLC), VP16-213 showed minimal activity, with only 4% of patients achieving partial responses lasting 5 to 6 months.

The main side effects of VP16-213 included myelosuppression, which was the dose-limiting toxicity, along with other adverse effects like nausea, vomiting, and chills during infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of VP16-213 in non-small cell lung cancer (NSCLC). Chapman, R., Itri, L., Gralla, R., et al.[2019]

The addition of the MMP inhibitor BMS-275291 to chemotherapy with paclitaxel and carboplatin in 75 patients with advanced non-small cell lung cancer (NSCLC) did not adversely affect tumor response, with an objective response rate of 21.9% compared to 36.4% in the placebo group.

BMS-275291 was well tolerated, showing similar levels of arthrotoxicity (31.6% in the BMS-275291 group vs. 29.7% in the placebo group) and a higher incidence of rash, indicating that it does not significantly increase toxicity compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer. Douillard, JY., Peschel, C., Shepherd, F., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Bevacizumab and non-small-cell lung cancer: starving the enemy to survive. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Management of patients with advanced non-small cell lung cancer: current and emerging options. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Emerging drugs for non-small-cell lung cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. [2005]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II evaluation of MGBG in non-small cell carcinoma of the lung. A Southwest Oncology Group study. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase II trial of VP16-213 in non-small cell lung cancer (NSCLC). [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer. [2015]