A Study Investigating BG-60366 in Adults With Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer

BeiGene

Status and phase: Enrolling; Phase 1

Conditions: EGFR Activating Mutation; Lung Cancer; EGFR Mutation-Related Tumors; NSCLC (Non-small Cell Lung Carcinoma); NSCLC; Non-Small Cell Lung Cancer

Treatments: Drug: BG-60366

Study type: Interventional

Funder types: Industry

Identifiers

NCT06685718

2024-517322-26-00 (EU Trial (CTIS) Number)

BG-60366-101

Details and patient eligibility

About

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.

Enrollment: 93 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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93 participants in 2 patient groups

Phase 1a: Dose Escalation and Safety Expansion

Experimental group

Description:

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

Treatment:

Drug: BG-60366

Phase 1b: Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: BG-60366