Clinical trial NCT06487858: A Study of BGB-R046 as Monotherapy and in Combination With Tislelizumab in Solid Tumors
Official title: A Multicenter Open-Label Phase 1a/1b Study to Evaluate the Safety and Preliminary Antitumor Activity of BGB-R046 as Monotherapy and in Combination With Tislelizumab in Participants With Selected Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: BGB-R046
First-in-human
Advanced solid tumor
Anti-Programmed Death-1 (Anti-PD1)
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-07-05
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human (FIH) study that will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-R046 as a single agent and in combination with tislelizumab (BGB-A317) in participants with advanced or metastatic immune-sensitive solid tumors.


Eligibility criteria: Inclusion Criteria:

* Participants able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection
* Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received standard systemic therapy or for whom standard treatment is not available, not tolerated, or determined not appropriate based on the investigator's judgement
* ≥ 1 measurable lesion per RECIST v1.1
* Able to provide an archived tumor tissue sample
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
* Adequate organ function
* Life expectancy \>12 weeks as determined by the investigator

Exclusion Criteria:

* Active leptomeningeal disease or uncontrolled, untreated brain metastasis
* Active autoimmune diseases or history of autoimmune diseases that may relapse
* Any malignancy ≤ 3 years before the first dose of study drug(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)
* Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s)
* History of interstitial lung disease, noninfectious pneumonitis (including immune mediated), or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases.
* Experienced ≥ Grade 3 imAE(s) on prior immuno-oncology agent (anti-PD-1, anti CTLA4, or other experimental drugs)
* Uncontrolled diabetes \> Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first dose of study drug(s).
* Infection (including tuberculosis infection, or other) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study drug(s)
* Immunodeficiency as assessed by the investigator to be not suitable for treatment with immune modulating anticancer agents

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: Up to approximately 2 years
measure: Phase 1a: Maximum Tolerated Dose (MTD) of BGB-R046
timeFrame: Up to approximately 2 years
measure: Phase 1a: Maximum Administered Dose (MAD) of BGB-R046
timeFrame: Up to approximately 2 years
measure: Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-R046
timeFrame: Up to approximately 2 years
measure: Phase 1b: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: Up to approximately 2 years
measure: Phase 1a: Time to Response (TTR)
timeFrame: Up to approximately 2 years
measure: Phase 1a: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 2 years
measure: Phase 1a and Phase 1b: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Phase 1a and Phase 1b: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Progression-free survival (PFS)
timeFrame: Up to approximately 2 years
measure: Phase 1b: Number of Participants with Adverse Events (AEs)
timeFrame: Up to approximately 2 years
measure: Phase 1a: Plasma concentrations of BGB-R046 analytes
timeFrame: Predose and at select time points in Cycles 1, 2 and 5; predose at select Cycles between Cycles 3 and 25 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days [± 7 days] after the last dose of study drug)
measure: Phase 1b: Plasma concentrations of BGB-R046 analytes
timeFrame: Predose and after end of infusion in Cycles 1 and 5; predose at select Cycles between Cycles 1 and 25 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days [± 7 days] after the last dose of study drug)
measure: Phase 1b: Plasma concentrations of tislelizumab
timeFrame: Predose and after end of infusion in Cycles 1 and 5; predose at select Cycles between Cycles 1 and 17 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days [± 7 days] after the last dose of study drug)
measure: Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-R046
timeFrame: Cycle 1 and Cycle 5 (each cycle is 21 days)
measure: Phase 1a and 1b: Minimum Observed Plasma Concentration (Ctrough) Of BGB-R046
timeFrame: Cycle 1 and Cycle 5 (each cycle is 21 days)
measure: Phase 1a and 1b: Area Under the Plasma Concentration-time Curve (AUC) of BGB-R046
timeFrame: Cycle 1 and Cycle 5 (each cycle is 21 days)
measure: Phase 1a and 1b: Terminal Half-Life (t1/2) of BGB-R046
timeFrame: Cycle 1 and Cycle 5 (each cycle is 21 days)
measure: Phase 1a and 1b: Incidence of Antidrug Antibodies (ADAs) to BGB-R046 and tislelizumab
timeFrame: Periodic sampling up to Cycle 25 (each cycle is 21 days) and at the first safety follow up visit up to approximately 2 years (conducted 30 days [± 7 days] after the last dose of study drug)
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jining
country: China
facility: Jining No Peoples Hospital West Branch
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: