BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04649385
• Other study ID #: BGB-A317-15025-101
• Secondary ID: CTR20212721
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2021
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: +1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 330
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• BGB-15025
Administered orally once or twice daily (QD or BID)
• Tislelizumab
Administered 200 mg intravenous (IV) infusion

Locations

Country	Name	City	State
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	One Clinical Research	Nedlands	Western Australia
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Ashford Cancer Centre Research Northeast	Windsor Gardens	South Australia
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnamsi	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul	Seoul Teugbyeolsi
Korea, Republic of	The Catholic University of Korea, Seoul St Marys Hospital	Seoul	Seoul Teugbyeolsi
New Zealand	Auckland City Hospital	Auckland
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	The University of Texas Md Anderson Cancer Center	Houston	Texas
United States	Ut Health San Antonio Mays Cancer Center	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  China,  Korea, Republic of,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: Number of participants with dose limiting toxicities (DLTs)	Participants will be considered evaluable for DLTs if they 1) received = 80% of each scheduled study treatment administration during the DLT assessment window and/or 2) experienced a DLT.	Up to 3 Years
Primary	Phase 1a: Number of Participants Experiencing Adverse Events (AEs)		Up to 4 Years
Primary	Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 4 years
Primary	The maximum tolerated dose (MTD) of BGB-15025	The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%	Up to 3 Years
Primary	Recommended Doses for Expansion (RDFE) of BGB-15025 monotherapy	The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%	Up to 3 years
Primary	RDFE of BGB-15025 in combination with tislelizumab	The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%	Up to 3 years
Primary	Phase 1b: Overall Response Rate (ORR) as assessed by the investigator		Up to 2 years
Secondary	Phase 1a: Overall Response Rate (ORR) as assessed by the investigator		Up to 3 years
Secondary	Duration Of Response (DOR) as assessed by the investigator		Up to 3 years
Secondary	Disease Control Rate (DCR) as assessed by the investigator		Up to 3 years
Secondary	Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Minimum observed plasma concentration (Cmin) of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Time to maximum plasma concentration (Tmax) of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Half-life of (t1/2) of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Area under the concentration-time curve (AUC) of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Apparent clearance (CL/F) of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Apparent volume of distribution (Vz/F) of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Accumulation Ratio for Cmax of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Accumulation Ratio for AUC of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1a: Metabolite to parent ratio for BGB-15025 and its metabolite		Predose up to 8 hours postdose
Secondary	Phase 1b: Number of Participants Experiencing Adverse Events (AEs)		Up to 3 years
Secondary	Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)		Up to 3 years
Secondary	Phase 1b: Plasma Concentrations of BGB-15025		Predose up to 8 hours postdose
Secondary	Phase 1b: Plasma Concentrations of the metabolite		Predose up to 8 hours postdose
Secondary	Phase 1b: Number of participants with dose limiting toxicities (DLTs)	Participants will be considered evaluable for DLTs if they 1) received = 80% of each scheduled study treatment administration during the DLT assessment window and/or 2) experienced a DLT.	Up to 1 year