An Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma

Phase 2TerminatedNCT05251948

Hoffmann-La Roche40 enrolled

Overview

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced gastric carcinoma (GC) or gastroesophageal junction carcinoma (GEJC). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population. Cohort 1 will enroll participants with inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology, who have not received prior systemic therapy for advanced or metastatic disease. Eligible participants will initially be randomly assigned to one of treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastric and Gastroesophageal Junction Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria for Stage 1: * ECOG Performance Status of 0 or 1 * Inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology * No prior systemic treatment for advanced or metastatic disease * Life expectancy \>= 3 months, as determined by the investigator * Human epidermal growth factor receptor 2 (HER2)-negative tumors * Measurable disease according to RECIST v1.1 * Adequate hematologic and end-organ function * Patients without hepatitis B virus (HBV) infection at screening * Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening * Negative HIV test at screening * For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, as outlined for each specific treatment arm * For men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm, as outlined for each specific treatment arm Exclusion Criteria for Stage 1: * Prior treatment with CD137 agonists or immune checkpoint blockade therapies * Treatment with investigational therapy within 28 days prior to initiation of study treatment * Any contraindications to any of the study drugs of the chemotherapy regimen * Eligible only for the control arm * Patients with a signet ring cells dominant carcinoma * Symptomatic, untreated, or actively progressing CNS metastases * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina * History of malignancy other than GC or GEJC within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death Exclusion Criteria for Tiragolumab-Containing Arm: * Prior treatment with an anti-TIGIT agent * Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening

Locations (11)

The General Hospital of People?s Liberation Army (301 Hospital)

Beijing, China

the First Hospital of Jilin University

Changchun, China

First Affiliated Hospital of Gannan Medical University

Ganzhou, China

The First Affiliated Hospital, Zhejiang University

Hangzhou, China

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, China

The Second Affiliated Hospital of Anhui Medical University

Hefei, China

Affiliated Hopsital of Jining Medical University

Jining, China

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

Nanjing, China

Nan Tong Tumor Hospital

Nantong, China

Shanxi Province Cancer Hospital

Taiyuan, China

...and 1 more locations

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions, ≥ 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \< 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off.

Time frame: Up to 42.1 months

Secondary Outcomes

Progression-free Survival (PFS) After Randomization

PFS after randomization was defined as the time from randomization to the first occurrence of PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. PFS was censored at the day of the last tumor assessment for participants who did not die or did not have documented PD. Median PFS was estimated using the Kaplan-Meier (K-M) method.

Time frame: From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to 42.1 months)

Overall Survival (OS) After Randomization

OS was defined as the time from randomization to death from any cause, regardless of stage. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. Median OS was estimated using the K-M method.

Time frame: From randomization to death from any cause (up to 42.1 months)

OS Rates at Specified Timepoints

OS was defined as the time from randomization to death from any cause, regardless of stage. OS rate at 6 and 12 months was defined as the percentage of participants who did not experience death from any cause at these timepoints from randomization. OS rates at the specified timepoints were estimated using the K-M method. Percentages have been rounded off.

Time frame: At Months 6 and 12

Duration of Response (DOR)

DOR was defined as time from the first occurrence of a documented objective response (OR), CR or PR to PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target/non-target lesions) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. DOR was censored at the day of the last tumor assessment for participants who did not die or did not have documented PD. Median DOR was estimated using the K-M method.

Time frame: From first occurrence of CR or PR to PD or death from any cause, whichever occurred first (up to 42.1 months)

Disease Control Rate (DCR)

DCR was defined as percentage of participants with stable disease (SD) for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Percentages have been rounded off.

Time frame: Up to 42.1 months

Number of Participants With Adverse Events (AEs)

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Time frame: Up to 42.1 months