Clinical trial NCT04649385: BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of HPK1 Inhibitor BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2020-12-02
Enrollment: 157
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: The primary objective of this study is to assess the safety and tolerability of BGB-15025 alone and in combination with tislelizumab; and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended Phase 2 doses (RP2D) of BGB-15025 alone and in combination with tislelizumab in participants with advanced solid tumors.


Eligibility criteria: Key Inclusion Criteria:

1. Phase 1a (dose escalation): Participants with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received standard systemic therapy or for whom treatment is not available, not tolerated or refused, and who have not received prior therapy targeting HPK1
2. Phase 1b (dose expansion): Participant with histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors, including non-small cell lung cancer, esophageal cancer or gastric/Gastroesophageal junction cancer (other solid tumors may be included) who have progressed following systemic anticancer therapies or have no prior systemic treatment for advanced disease
3. At least 1 measurable lesion as defined per RECIST 1.1.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
5. Adequate organ function as indicated by the following laboratory values up to first dose of study treatment: Hemoglobin≥ 90 g/L, Absolute neutrophil count ≥ 1.5 x 109/L , Serum total bilirubin ≤ 1.5 x ULN (\< 3 x ULN for participants with Gilbert syndrome ), AST and ALT≤ 2.5 x ULN

Key Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled and untreated brain metastasis.
2. Active autoimmune diseases or history of autoimmune diseases that may relapse
3. Any active malignancy ≤ 2 years before the first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent
4. 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 treatment
5. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including but not limited to pulmonary fibrosis, acute lung diseases, etc.

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

Primary outcomes:
measure: Phase 1a: Number of participants with dose limiting toxicities (DLTs)
timeFrame: Up to 3 Years
measure: Phase 1a: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 4 Years
measure: Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to 4 years
measure: The maximum tolerated dose (MTD) of BGB-15025
timeFrame: Up to 3 Years
measure: Recommended Doses for Expansion (RDFE) of BGB-15025 monotherapy
timeFrame: Up to 3 years
measure: RDFE of BGB-15025 in combination with tislelizumab
timeFrame: Up to 3 years
measure: Phase 1b: Overall Response Rate (ORR) as assessed by the investigator
timeFrame: Up to 2 years
Secondary outcomes:
measure: Phase 1a: Overall Response Rate (ORR) as assessed by the investigator
timeFrame: Up to 3 years
measure: Duration Of Response (DOR) as assessed by the investigator
timeFrame: Up to 3 years
measure: Disease Control Rate (DCR) as assessed by the investigator
timeFrame: Up to 3 years
measure: Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Minimum observed plasma concentration (Cmin) of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Time to maximum plasma concentration (Tmax) of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Half-life of (t1/2) of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Area under the concentration-time curve (AUC) of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Apparent clearance (CL/F) of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Apparent volume of distribution (Vz/F) of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Accumulation Ratio for Cmax of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Accumulation Ratio for AUC of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1a: Metabolite to parent ratio for BGB-15025 and its metabolite
timeFrame: Predose up to 8 hours postdose
measure: Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 3 years
measure: Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to 3 years
measure: Phase 1b: Plasma Concentrations of BGB-15025
timeFrame: Predose up to 8 hours postdose
measure: Phase 1b: Plasma Concentrations of the metabolite
timeFrame: Predose up to 8 hours postdose
measure: Phase 1b: Number of participants with dose limiting toxicities (DLTs)
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Tennessee Oncology, Pllc Nashville
state: Tennessee
city: San Antonio
country: United States
facility: Ut Health San Antonio Mays Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Windsor Gardens
country: Australia
facility: Ashford Cancer Centre Research Northeast
state: South Australia
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
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 Medicine
state: Zhejiang
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: SeochoGu
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St Marys Hospital
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
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
Study officials:
References: