A Study of Gimistotug (BGB-A445) in Combination With Other Investigational Agents in Participants With Non-Small Cell Lung Cancer

A Phase 2, Open-label, Randomized, Multi-arm Study of BGB-A445 in Combination With Investigational Agents in Non-Small Cell Lung Cancer Patients Previously Treated With Anti-PD-(L)1 Antibody

The main objective of this study was to evaluate the anti-tumor activity of gimistotug (BGB-A445) plus investigational agents in participants with non-small cell lung cancer (NSCLC).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Gimistotug; Drug: BGB-15025

Detailed Description

This study tested whether gimistotug in combination with other agents could help treat participants with non-small cell lung cancer (NSCLC) who were already treated with other anticancer agents, including anti-programmed cell death protein-1 (anti-PD-1) and anti-programmed cell death protein ligand-1 (anti-PD-L1) antibodies and platinum-based chemotherapy. The main goal of this study was to see if gimistotug could increase participant response to treatment, also called the overall response rate.

Only a portion of patients with advanced solid tumors have a durable response to currently available treatments. This represents an unmet medical need to develop improved therapeutic options. Combining immunotherapies with agents having different mechanism of action might improve outcomes for these patients.

This study was designed as a proof of concept to show that gimistotug-based combination treatment may be able to improve responses and clinical benefit in patients with NSCLC. Treatments in all cohorts was administered up to 36 cycles (approximately 2 years) until participants experienced no benefits, too many side effects, or withdrew consent.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400042
      • Daping Hospital, Third Military Medical University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Gansu Provincial Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510405
      • The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Wuxi, Jiangsu, China, 214122
      • Affiliated Hospital of Jiangnan University South Campus
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Shandong
    • Taian, Shandong, China, 271099
      • The Second Affiliated Hospital of Shandong First Medical University
    • Weihai, Shandong, China, 264299
      • Weihai Municipal Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Fudan University Shanghai Cancer Center
  • Shanxi
    • Taiyuan, Shanxi, China, 030013
      • Shanxi Provincial Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
• South Korea
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • National Cancer Center
    • Suwon, Gyeonggi-do, South Korea, 16247
      • The Catholic University of Korea, St Vincents Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03722
      • Severance Hospital Yonsei University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Advanced or metastatic NSCLC (nonsquamous or squamous) that is histologically or cytologically confirmed
• Participants who have received no more than 2 lines of prior systemic therapies which must include anti-programmed cell death protein ligand-1 (anti-PD-(L)1) treatment and a platinum-based chemotherapy administered in combination with, or sequentially before or after the anti-PD-(L)1 treatment
• At least 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ function as indicated by laboratory values during screening

Exclusion Criteria:

• With mixed small cell lung cancer
• Has received prior therapy targeting OX40 or any other T-cell agonists
• Has received prior therapy containing docetaxel and/or ramucirumab for advanced or metastatic NSCLC
• Has received any Chinese herbal medicine or Chinese patent medicines used to control cancer ≤ 14 days before the first dose of study drug(s)
• Active leptomeningeal disease or uncontrolled and untreated brain metastasis

NOTE: Other criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gimistotug + Docetaxel; Participants received gimistotug and docetaxel 75 mg/m^2 both by intravenous infusion once every 3 weeks until disease progression, intolerable toxicity, withdrawal of informed consent, or other discontinuation criterion were met.	Drug: Docetaxel; 75 milligrams per square meter (mg/m^2) administered intravenously; Drug: Gimistotug; Administered intravenously; Other Names: BGB-A445
Experimental: Gimistotug + BGB-15025; Participants received gimistotug by intravenous infusion once every 3 weeks and BGB-15025 orally once daily during each 3-week cycle until disease progression, intolerable toxicity, withdrawal of informed consent, or other discontinuation criterion were met.	Drug: Gimistotug; Administered intravenously; Other Names: BGB-A445; Drug: BGB-15025; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate (ORR) is defined as the percentage of participants with best overall response (BOR) of a confirmed complete response (CR) or partial response (PR) as assessed by the investigators per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1. CR is defined as: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm.; Disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes must be nonpathological in size (< 10 mm short axis).; No new lesions. PR is defined as: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.; Non-progressive disease with regard to non-target lesions, persistence of 1 or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits.; No new lesions.	Response was assessed every 6 weeks for the first 9 months and every 12 weeks thereafter; maximum time on follow-up was up to 13.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. An SAE is any untoward medical occurrence that, at any dose, meet any of the following criteria: Results in death; Is life-threatening; Requires hospitalization or prolongation of existing hospitalization; Results in disability/incapacity; Is a congenital anomaly/birth defect; Is considered a significant medical AE by the investigator or the sponsor based on medical judgement	From first dose of study drug to 30 days after last dose. Maximum time on treatment was 11.2 months
Duration of Response (DOR)	DOR is defined as the time from the first determination of an objective response as assessed by the investigator per RECIST v1 until the first documentation of progression or death, whichever comes first. Median DOR was estimated using the Kaplan-Meier method.	From first dose to the end of study; maximum time on follow-up was up to 13.5 months.
Disease Control Rate (DCR)	DCR is defined as the percentage of participants with BOR of a CR, PR, or stable disease. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, with no new lesions.	From first dose to the end of study; maximum time on follow-up was up to 13.5 months
Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with BOR of a CR, PR, or stable disease lasting ≥ 24 weeks.	Assessed from first dose to the end of the study. Response was assessed every 6 weeks for the first 9 months and every 12 weeks thereafter; maximum time on follow-up was up to 13.5 months
Serum Concentrations of Gimistotug		Cycle 1 Day 1 0.5 hours post-dose, Cycle 2 Day 1 predose, Cycle 5 Day 1 pre- and 0.5 hours post-dose, Cycle 9 Day 1 Predose, End of Treatment visit (30 days after last dose)
Plasma Concentrations of BGB-15025		Cycle 1 Day 1 2 hours and 4-6 hours post-dose, Cycle 1 Day 8 pre-dose, Cycle 1 Day 15 pre-dose, Cycle 2 Day 1 pre-dose and 2 hours and 4-6 hours post-dose, Cycle 3 Day 1 pre-dose
Number of Participants With Anti-Drug Antibodies to Gimistotug		Up to 30 days following last dose. Maximum time on treatment was 11.2 months.

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2023
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: September 6, 2023
• First Posted (Actual): September 8, 2023

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; PD-L1
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel
• Other Study ID Numbers: BGB-LC-203; CTR20233070 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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