Phase 1a/1b, Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of a CDAC Degrading EGFR, BG-60366, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

Plain English Summary

A Study Investigating BG-60366 in Adults With Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer is a Phase 1 clinical trial sponsored by BeOne Medicines studying Non-Small Cell Lung Cancer, Lung Cancer, NSCLC, NSCLC (Non-small Cell Lung Carcinoma), EGFR Activating Mutation, EGFR Mutation-Related Tumors. This trial tests a new drug called BG-60366, designed to target a specific gene (EGFR) that drives certain types of lung cancer. It is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific EGFR gene mutation and has not responded to previous treatments. Participants will take the study drug orally, and their health will be closely monitored. The study has different phases to find the right dose and see how well the drug works. Alternative treatments may include chemotherapy or other targeted therapies, depending on the patient's specific situation and prior treatments. The trial aims to enroll 33 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with non-small cell lung cancer (NSCLC) confirmed to have a specific EGFR gene mutation. Patients whose cancer has progressed after treatment with a third-generation EGFR-targeted drug, and who are not eligible for or have progressed on standard chemotherapy. Patients with documented EGFR resistance mutations (like C797s) are also included. Individuals with stable general health (ECOG status of 0 or 1) and adequate organ function can participate. Those with active brain metastases, certain lung conditions, or who have previously received similar targeted drugs may not be eligible. This trial is studying Non-Small Cell Lung Cancer, Lung Cancer, NSCLC, NSCLC (Non-small Cell Lung Carcinoma), EGFR Activating Mutation, EGFR Mutation-Related Tumors, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will determine how safe the drug is and what dose is best for future studies, and will also assess how well the drug shrinks tumors or controls their growth. The specific primary outcome measures are: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) (From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 18 months)); Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) (Approximately 1 month); Phase 1a: Recommended dose(s) for expansion (RDFE) of BG-60366 (Approximately 18 months); Phase 1b: Number of Participants with Adverse Events and Serious Adverse Events (From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 24 months)); Phase 1b: Overall Response Rate (ORR) (Approximately 24 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a critical need for new treatments for patients with EGFR-mutant non-small cell lung cancer who have developed resistance to existing therapies. This research targets Non-Small Cell Lung Cancer, Lung Cancer, NSCLC, NSCLC (Non-small Cell Lung Carcinoma), EGFR Activating Mutation, EGFR Mutation-Related Tumors, where improved treatment options are needed.

Investor Insight

This early-phase trial of a novel EGFR-targeting drug represents a potential new option in a competitive market for lung cancer treatments, with a focus on overcoming resistance mechanisms. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your lung cancer has an EGFR mutation and if you have developed resistance to prior treatments. Understand that this is an open-label study, meaning both you and the study team will know you are receiving the study drug. Participation involves regular clinic visits for drug administration, blood tests, scans to check your cancer, and monitoring for side effects. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 33 participants

Interventions

• DRUG: BG-60366 — Administered orally

Primary Outcomes

• Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) (From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 18 months))
• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) (Approximately 1 month)
• Phase 1a: Recommended dose(s) for expansion (RDFE) of BG-60366 (Approximately 18 months)
• Phase 1b: Number of Participants with Adverse Events and Serious Adverse Events (From first dose of the study drug to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 24 months))
• Phase 1b: Overall Response Rate (ORR) (Approximately 24 months)

Secondary Outcomes

• Phase 1a: Overall Response Rate (ORR) (Approximately 24 months)
• Phase 1a and 1b: Duration of Response (DOR) (Approximately 24 months)
• Phase 1a and 1b: Time to Response (TTR) (Approximately 24 months)
• Phase 1b: Progression-Free Survival (PFS) (Approximately 24 months)
• Phase 1b: Disease Control Rate (DCR) (Approximately 24 months)

Full Eligibility Criteria

Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of NSCLC, carrying an EGFR activating mutation prior to receiving standard EGFR-tyrosine kinase inhibitor (EGFR-TKI)
* Phase 1a general inclusion criteria:

  * Disease progression on prior third-generation EGFR-TKI for advanced or metastatic disease, and either progressed or ineligible for currently available standard-of-care treatment (eg, platinum-based chemotherapy) after EGFR-TKI treatment
* Phase 1a safety expansion

  * Documentation of EGFR resistance mutations (ie, C797s)
* At least ≥ 1 evaluable lesion (for Phase 1a Dose Escalation) or at least ≥ 1 measurable lesion (for Phase 1a Safety Expansion or Phase 1b Dose Expansion) per RECIST v1.1
* EGFR resistance mutations may be detected locally either from tumor tissue or circulating tumor DNA (ctDNA) in blood, and samples used for detection of resistance mutations must be collected after progression on the most recent systemic antitumor treatment
* Adequate organ function
* Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

Exclusion Criteria:

* Any previous histologic or cytologic evidence of small cell or combined small cell/non-small cell disease in the archival tumor tissue or tumor biopsy before enrollment
* Symptomatic spinal cord compression
* Brain metastases which are symptomatic and/or requiring emergency treatment (eg, starting steroid, or stereotactic radiation/whole-brain radiation within 2 weeks before first dose of study drug)
* Prior treatment with fourth-generation EGFR-TKI, other CDAC/proteolysis-targeting chimeras (PROTAC) compounds targeting EGFR mutations, or other drugs with the mechanism of action specifically targeting EGFR resistance mutations (eg, C797X) (except for the first- to third-generation EGFR-TKIs)
* Any history of interstitial lung disease (ILD) or ≥ Grade 2 noninfectious pneumonitis ≤ 2 years before the first dose of study drug, or has current ILD/noninfectious pneumonitis, or where suspected active ILD/noninfectious pneumonitis cannot be ruled out by imaging during screening
* Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial Locations

• University of Colorado, Denver, Colorado, United States
• Dana Farber Cancer Institute, Boston, Massachusetts, United States
• Washington University School of Medicine Siteman Cancer Center, St Louis, Missouri, United States
• Memorial Sloan Kettering Cancer Center Mskcc, New York, New York, United States
• Ohio State University, Columbus, Ohio, United States
• The University of Texas Md Anderson Cancer Center, Houston, Texas, United States
• Blacktown Cancer and Haematology Centre, Blacktown, New South Wales, Australia
• Liverpool Hospital, Liverpool, New South Wales, Australia
• Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
• Cancer Research South Australia, Adelaide, South Australia, Australia
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• Lung Cancer
• EGFR-mutated cancers
• EGFR-TKI resistance
• Metastatic Lung Cancer
• Oncology
• Targeted Cancer Therapy
• Drug Development
• Clinical Trials
• Cancer Genomics

More Non-Small Cell Lung Cancer Trials

View all Non-Small Cell Lung Cancer clinical trials