Clinical trial NCT06585488: A First-in-human Study of BGB-53038, a Pan-KRAS Inhibitor, Alone or in Combinations in Participants With Advanced or Metastatic Solid Tumors With KRAS Mutations or Amplification
Official title: A Phase 1a/1b Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-53038, a Pan-KRAS Inhibitor, as Monotherapy or in Combinations in Patients With Advanced or Metastatic Solid Tumors With KRAS Mutations or Amplifications
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Solid Tumors
Advanced Non-squamous Non-small-cell Lung Cancer
Advanced Colorectal Cancer
Advanced Pancreatic Ductal Adenocarcinoma
Advanced Gastric Cancer
Advanced Gastroesophageal Junction Cancer
Advanced Esophageal Adenocarcinoma
Keywords: KRAS wild type amplification
Metastatic Solid Tumors
Advanced Non-squamous Non-small-cell Lung Cancer
Advanced Colorectal Cancer
Advanced Pancreatic Ductal Adenocarcinoma
Advanced Gastric Cancer
Advanced Gastroesophageal Junction Cancer
Advanced Esophageal Adenocarcinoma
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-09-05
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human (FIH), open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-53038 as monotherapy in participants with advanced or metastatic solid tumors harboring KRAS mutations or amplification, as well as when used in combination with tislelizumab (also known as BGB-A317) in participants with nonsquamous non-small cell lung cancer (NSCLC) and used in combination with cetuximab in participants with colorectal cancer (CRC). The study consists of 2 phases: Phase 1a Dose Escalation and Safety Expansion and Phase 1b Dose Expansion.


Eligibility criteria: Inclusion Criteria:

1. Must sign a written ICF; and understand and agree to comply with the requirements of the study and the schedule of activities.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
3. Participants must have evidence of a KRAS mutation or wild-type amplification (copy number ≥ 8) based on testing of either tumor tissue or liquid biopsy (blood or plasma) as determined by local laboratory
4. Able to provide an archived tumor tissue sample or fresh biopsy sample.
5. ≥ 1 measurable lesion per RECIST v1.1.
6. Adequate organ function.
7. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, for \> 7 days after the last dose of BGB-53038, \> 120 days after the last dose of tislelizumab, or \> 2 months after the last dose of cetuximab, whichever is later
8. Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study treatment period and for ≥ 4 months after the last dose of study drug(s).

Exclusion Criteria:

1. Participants with tumors harboring KRAS G12R mutation.
2. Participants who have prior therapy with other anti-RAS treatment, including, but not limited to, therapy targeting specific KRAS allele mutation inhibitors, pan-KRAS inhibitors, and other pan-RAS inhibitors
3. Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis. Participants with a history of treated and, at the time of screening, stable CNS metastases are eligible, provided they meet select criteria.
4. Any malignancy ≤ 2 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
5. Participants with untreated chronic hepatitis B or chronic HBV carriers with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening. Participants with active hepatitis C.
6. Participants with clinically significant infections (including tuberculosis infection) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study treatment.

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

Primary outcomes:
measure: Phase 1a: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to approximately 2 years
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-53038
timeFrame: Up to approximately 2 years
measure: Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-53038
timeFrame: Up to approximately 2 years
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-53038
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Phase 1a: Single-dose and steady-state area under the concentration-time curve (AUC) of BGB-53038
timeFrame: Up to approximately 2 years
measure: Phase 1a: Single-dose and steady-state Half-life (t1/2) of BGB-53038
timeFrame: Up to approximately 2 years
measure: Phase 1a: Single-dose and steady-state maximum observed plasma concentration (Cmax) of BGB-53038
timeFrame: Up to approximately 2 years
measure: Phase 1a: Single-dose and steady-state trough concentration (Ctrough) of BGB-53038
timeFrame: Up to approximately 2 years
measure: Phase 1b: ORR
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Time to Response (TRR)
timeFrame: Up to approximately 2 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to approximately 2 years
measure: Plasma concentrations of BGB-53038
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center (Nccc)
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer At Johns Hopkins
state: Maryland
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: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
state: Shanxi
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
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: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Madrid
country: Spain
facility: Start Madrid Fundacion Jimenez Diaz
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia Incliva
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: