A Study to Investigate the Antitumor Activity, Safety, Tolerability, and Pharmacokinetics of BGB-A445 in Combination With Tislelizumab in Participants With Select Advanced Solid Tumors.

Phase 1b/2 Study Investigating the Antitumor Activity, Safety, Tolerability, and Pharmacokinetics of the Anti-OX40 Agonist Monoclonal Antibody BGB-A445 in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced or Metastatic Urothelial Carcinoma, Renal Cell Carcinoma, or Melanoma

The objective of this study is to assess the overall response rate, evaluate the antitumor activity, and characterize the safety and tolerability of BGB-A445 alone or in combination with tislelizumab in participants With Advanced or Metastatic Urothelial Carcinoma (UC), Renal Cell Carcinoma (RCC), or Melanoma

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Renal Cell Carcinoma; Urothelial Carcinoma
• Intervention / Treatment: Drug: Tislelizumab; Drug: BGB-A445

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1.877.828.5568; Email: clinicaltrials@beigene.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Recruiting
      • Fujian Cancer Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Recruiting
      • Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat Sen University Cancer Center
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Recruiting
      • The Tumor Hospital Affiliated to Guangxi Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450099
      • Recruiting
      • The Third Peoples Hospital of Zhengzhou
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Recruiting
      • Liaoning Cancer Hospital and Institute
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
    • Jining, Shandong, China, 272002
      • Recruiting
      • Jining No Peoples Hospital Main Branch
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Recruiting
      • Shanxi Provincial Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin, China, 300000
      • Recruiting
      • The Second Affiliated Hospital of Tianjin Medical University
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants described in the following cohorts, who have received at least 1 but no more than 3 lines of prior systemic therapy for histologically or cytologically confirmed advanced and/or metastatic UC, RCC or melanoma Participants must not have received prior therapy targeting OX40 or any other T-cell agonists
2. Has at least 1 measurable lesion as defined per RECIST v1.1.
3. Participants must be able to provide an archived formalin-fixed paraffin embedded (FFPE) tumor tissue sample
4. ECOG PS ≤ 1 (Participants with UC could have an ECOG PS ≤ 2) and a life expectancy of≥ 3 months
5. Adequate organ function as indicated by the laboratory values up to the first dose of study drug(s)

Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled brain metastasis
2. Active autoimmune diseases or history of autoimmune diseases that may relapse or history of life-threatening toxicity related to prior immune therapy
3. 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

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 drug(s), with the following exceptions:

   1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
   2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
   3. 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)
5. With uncontrolled diabetes, or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or ≥ Grade 3 hypoalbuminemia occurring ≤ 14 days before the first dose of study drug(s)

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Previously Treated UC Cohort A; BGB-A445 Monotherapy	Drug: BGB-A445; administered intravenously
Experimental: Previously Treated UC Cohort B; BGB-A445 and Tislelizumab	Drug: Tislelizumab; administered intravenously; Drug: BGB-A445; administered intravenously
Experimental: Previously Treated RCC Cohort C; BGB-A445 Monotherapy	Drug: BGB-A445; administered intravenously
Experimental: Previously Treated RCC Cohort D; BGB-A445 and Tislelizumab	Drug: Tislelizumab; administered intravenously; Drug: BGB-A445; administered intravenously
Experimental: Previously Treated Melanoma Cohort E; BGB-A445 Monotherapy	Drug: BGB-A445; administered intravenously
Experimental: Previously Treated Melanoma Cohort F; BGB-A445 and Tislelizumab	Drug: Tislelizumab; administered intravenously; Drug: BGB-A445; administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Determined from investigator derived tumor assessments as per RECIST 1.1	Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Duration of Response (DOR)	Determined from investigator derived tumor assessments as per RECIST 1.1	Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Disease-Control Rate (DCR)	Determined from investigator derived tumor assessments as per RECIST 1.1	Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Clinical benefit rate (CBR)	Determined from investigator derived tumor assessments as per RECIST 1.1	Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Number of Participants Experiencing Adverse Events (AEs)	As determined per National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed	Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Number of Participants Experiencing Serious Adverse Events (SAEs)	As determined per National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed	Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Serum Concentration of BGB-A445		60 minutes predose up to 72 hours postdose
Serum Concentration of tislelizumab		60 minutes predose up to 72 hours postdose
Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies		Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Actual): December 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma; Melanoma; advanced solid tumors; Renal Cell Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Melanoma; Carcinoma, Transitional Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: BGB-A317-A445-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No