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

BeiGene35 enrolled

Overview

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).

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-Small Cell Lung Cancer

Interventions

GimistotugDRUG

Administered intravenously

DocetaxelDRUG

75 milligrams per square meter (mg/m\^2) administered intravenously

BGB-15025DRUG

Administered orally

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (18)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

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.

Time frame: 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 Outcomes

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

Time frame: 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.

Data from ClinicalTrials.gov

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