Safety and Preliminary Effectiveness of BGB-A445 in Combination With Tislelizumab in Participants With Advanced Solid Tumors

NCT04215978 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: BGB-A317-A445-1012022-501177-39-00CTR20220453
• Study Type: interventional
• Target: 204
• Locations: 8 countries
• Sites: 30

Brief Summary

The purpose of this study is to assess the safety and tolerability of BGB-A445 alone and in combination with tislelizumab in participants with advanced solid tumors; and to determine the maximum tolerated dose(s) (MTD) or maximum administered dose(s) (MAD) and recommended Phase 2 doses (RP2D) of BGB-A445 alone and in combination with tislelizumab.

Conditions

Advanced Solid Tumor; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma (HNSCC); Nasopharyngeal Carcinoma (NPC)

Keywords

OX40; PD-1

Outcome Measures

Primary Outcomes (6)

• Phase 1a: Number of Participants Experiencing Adverse Events (AEs)

  Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy

• Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs)

  Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy

• Phase 1a: Number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria

  Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy

• Phase 1a: Maximum Tolerated Dose (MTD) of BGB-A445

  The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%

  Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

• Phase 1b: RP2D of BGB-A445 when Administered Alone

  Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

• Phase 1b: Overall Response Rate (ORR) as Assessed by the Investigator

  ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)

  Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

Secondary Outcomes (25)

• Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator

  Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

• Phase 1a: Duration of Response (DOR) as Assessed by the Investigator

  Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

• Phase 1a: Disease-Control Rate (DCR) as Assessed by the Investigator

  Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

• Phase 1a: Serum Concentration of BGB-A445

  60 minutes predose up to 72 hours postdose

• Phase 1a: Serum Concentration of tislelizumab

  60 minutes predose up to 72 hours postdose

Study Arms (5)

Phase 1a: BGB-A445 Monotherapy

EXPERIMENTAL

Dose Escalation Part A: Participants will receive intravenous (IV) infusion of BGB-A445 in sequential cohorts of approximately 8 increasing dose levels on day 1 of each 21-day cycle

Drug: BGB-A445

Phase 1a: BGB-A445 + Tislelizumab Combination Therapy

EXPERIMENTAL

Dose Escalation Part B: Participants will receive IV infusion of BGB-A445 in sequential cohorts of approximately 6 increasing dose levels plus 200mg tislelizumab on day 1 of each 21-day cycle

Drug: BGB-A445; Drug: tislelizumab

Phase 1b:BGB-A445 Monotherapy

EXPERIMENTAL

Dose Expansion Part A: Participants will receive recommended doses of IV BGB-A445 as determined from Phase 1a Dose Escalation; BGB-A445 will be evaluated in two tumor types

Drug: BGB-A445

Phase 1b: BGB-A445 + Tislelizumab and Chemotherapy Combination Therapy

EXPERIMENTAL

Dose Expansion Part B: Participants will receive recommended dose IV infusion of BGB-A445 plus 200mg tislelizumab and chemotherapy

Drug: BGB-A445; Drug: tislelizumab

Phase 1b: BGB-A445 Monotherapy

EXPERIMENTAL

Dose Expansion Part C: Participants will receive 1 dose level of BGB-A445

Drug: BGB-A445

Interventions

BGB-A445 DRUG

Administered as specified in the treatment arm

Also known as: Gimistotug

Phase 1a: BGB-A445 + Tislelizumab Combination Therapy; Phase 1a: BGB-A445 Monotherapy; Phase 1b: BGB-A445 + Tislelizumab and Chemotherapy Combination Therapy; Phase 1b: BGB-A445 Monotherapy; Phase 1b:BGB-A445 Monotherapy

tislelizumab DRUG

Administered as specified in the treatment arm

Also known as: BGB-A317

Phase 1a: BGB-A445 + Tislelizumab Combination Therapy; Phase 1b: BGB-A445 + Tislelizumab and Chemotherapy Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Phase 1a (dose escalation): Participants with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for whom treatment is not available, not tolerated or refused.
• Enrollment will be limited to participants with advanced solid tumors for which there is clinical evidence of response to T cell based immuno-oncology agents (eg, anti PD 1) or other scientific evidence in support of an immunologically sensitive tumor type.
• Participant has not received prior therapy targeting OX40 or any other T cell agonist therapy (prior checkpoint inhibitor therapy is allowed)
• \. Phase 1b, the dose expansion phase, aims to include participants in specific tumor type cohorts who do not have access to standard systemic treatment, cannot tolerate it, or it is deemed inappropriate by the investigator. Cohort 1 focuses on non-small cell lung cancer (NSCLC) patients with advanced or metastatic disease, while Cohort 2 involves individuals with recurrent or metastatic head and neck squamous cell cancer (HNSCC). Cohort 3 includes participants with nasopharyngeal carcinoma (NPC), and Cohort 4 is for NSCLC patients with PD-L1 expression of at least 50%. Each cohort has specific eligibility criteria related to prior therapies, tumor characteristics, and treatment-free intervals.
• \. Has at least 1 measurable lesion as defined per RECIST 1.1. The target lesion(s) selected have not been previously treated with local therapy OR the target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST 1.1 4. Participants should be able to provide tumor tissue sample 5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 and a life expectancy of ≥ 6 months.
• \. Adequate organ function as indicated by the following laboratory values up to first dose of study drug
• a. Participants must not have required blood transfusion or growth factor support ≤ 14 days before sample collection for the following:
• Absolute neutrophil count ≥ 1.5 x 10\^9/L
• Platelet count ≥ 75 x 10\^9/L
• Hemoglobin ≥ 90 g/L
• b. Estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 determined by the Cockcroft-Gault formula without correction for body surface area (BSA)
• The estimated GFR for participants with renal cell carcinoma must be ≥ 30 mL/min/1.73 m\^2 by the Cockcroft-Gault formula
• c. Serum total bilirubin ≤ 1.5 x ULN (\< 3 x ULN for participants with Gilbert syndrome) d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN;
• ≤ 5 x ULN for participants with hepatocellular carcinoma or liver metastases

You may not qualify if:

• Active leptomeningeal disease or uncontrolled brain metastasis. Participants with equivocal findings or with confirmed brain metastases are eligible for enrollment provided they are asymptomatic and radiologically stable without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s)
• Active autoimmune diseases or history of autoimmune diseases that may relapse or history of life-threatening toxicity related to prior immune therapy, with the following exceptions:
• Controlled type 1 diabetes
• Hypothyroidism (provided it is managed with hormone-replacement therapy only)
• Controlled celiac disease
• Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)
• Any other disease that is not expected to recur in the absence of external triggering factors (requires consultation with the medical monitor prior to enrollment)
• Any active malignancy ≤ 2 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), with the following exceptions:
• Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
• Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
• Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a nonautoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen)
• Any major surgical procedure occurring ≤ 28 days before the first dose of study drug(s). If surgical procedure occurs \> 28 days, they must have recovered adequately from the toxicity

Sponsors & Collaborators

• BeiGene: lead

Study Sites (30)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

California Cancer Associates for Research & Excellence (cCARE)

San Diego, California, 92127, United States

Location

UPMC Hillman Cancer Center (Univ Of Pittsburgh)

Pittsburgh, Pennsylvania, 15232, United States

Location

Blacktown Cancer And Haematology Centre

Blacktown, New South Wales, 2148, Australia

Location

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

Union Hospital Of Tongji Medical College, Huazhong University Of Science And Technology

Wuhan, Hubei, 430022, China

Location

The Second Xiangya Hospital Of Central South University

Changsha, Hunan, 410011, China

Location

Jinan Central Hospital

Jinan, Shandong, 250013, China

Location

Linyi Cancer Hospital

Linyi, Shandong, 276001, China

Location

Affiliated Zhongshan Hospital Of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

University of Malaya Medical Centre

Kuala Lumpur, 50603, Malaysia

Location

Sarawak General Hospital

Kuching, 93586, Malaysia

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

National Cancer Center (NCC)

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Cha Bundang Medical Center, Cha University

Gyeonggido, Gyeonggi-do, 13496, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, 13620, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 03722, South Korea

Location

Changhua Christian Hospital

Changhua, NAP, 500-06, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

King Chulalongkorn Memorial Hospital (Chulalongkorn University)

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital Mahidol University

Bangkok, 10400, Thailand

Location

Srinagarind Hospital (Khon Kaen University)

Muang, 40002, Thailand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Nasopharyngeal Carcinoma

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2019
• First Posted: January 2, 2020
• Study Start: January 30, 2020
• Primary Completion: January 24, 2025
• Study Completion: January 24, 2025
• Last Updated: October 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

TH (3); TW (2); US (3); MY (2); KR (5); AU (7); CN (7); NZ (1)