Clinical trial NCT06685718: A Study Investigating BG-60366 in Adults With Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Lung Cancer
NSCLC
NSCLC (Non-small Cell Lung Carcinoma)
EGFR Activating Mutation
EGFR Mutation-Related Tumors
Keywords: lung cancer
non-small cell lung cancer
NSCLC
EGFR activating mutation
EGFR resistant mutation
advanced or metastatic non-small cell lung cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-11-12
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


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.

Primary outcomes:
measure: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
timeFrame: Approximately 1 month
measure: Phase 1a: Recommended dose(s) for expansion (RDFE) of BG-60366
timeFrame: Approximately 18 months
measure: Phase 1b: Number of Participants with Adverse Events and Serious Adverse Events
timeFrame: 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)
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Phase 1a: Overall Response Rate (ORR)
timeFrame: Approximately 24 months
measure: Phase 1a and 1b: Duration of Response (DOR)
timeFrame: Approximately 24 months
measure: Phase 1a and 1b: Time to Response (TTR)
timeFrame: Approximately 24 months
measure: Phase 1b: Progression-Free Survival (PFS)
timeFrame: Approximately 24 months
measure: Phase 1b: Disease Control Rate (DCR)
timeFrame: Approximately 24 months
measure: Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BG-60366
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BG-60366
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Apparent terminal elimination half-life (t1/2) of BG-60366
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Area under the concentration-time curve (AUC) for BG-60366
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BG-60366
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Apparent total clearance (CL/F) of BG-60366
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Apparent volume of distribution (Vz/F) of BG-60366
timeFrame: Twice in the first 3 months
measure: Phase 1a and 1b: Accumulation Ratio (AR) of BG-60366
timeFrame: Once in the first three months
measure: Phase 1a and 1b: Plasma concentrations of BG-60366
timeFrame: Approximately up to 6 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research South Australia
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Barretos
country: Brazil
facility: Fundacao Pio Xii Hospital de Amor de Barretos
city: Natal
country: Brazil
facility: Liga Norte Riograndene Contra O Cancer
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas Da Pucrs
city: Salvador
country: Brazil
facility: Hospital Sao Rafael (Rede Dor)
city: Sao Jose Do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
city: Sao Paulo
country: Brazil
facility: Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Vitoria
country: Brazil
facility: Hospital Santa Rita de Cassia Afecc
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital Huifu Branch
state: Guangdong
city: Nanning
country: China
facility: The Tumor Hospital Affiliated to Guangxi Medical Universitywuxiang Branch
state: Guangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicineqiantang Branch
state: Zhejiang
city: Bologna
country: Italy
facility: Irccs Azienda Ospedaliero Universitaria Bologna
city: Monza
country: Italy
facility: Fondazione Irccs San Gerardo Dei Tintori Sc Oncologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: SeowonGu CheongjuSi
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbukdo
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Auckland
country: New Zealand
facility: Harbour Cancer and Wellness
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Madrid
country: Spain
facility: Hospital Universitario de Octubre
city: Majadahonda
country: Spain
facility: H Puerta de Hierro Majadahonda
city: Dusit
country: Thailand
facility: Ramathibodi Hospital Mahidol University
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital (Prince of Songkhla University)
city: Muang
country: Thailand
facility: Srinagarind Hospital (Khon Kaen University)
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: