MedPath

A phase 2 double-blind study of Toriplaimab with chemotherapy vs placebo with chemotherapy in patients diagnosed with HER2-negative, untreated, advanced or metastatic stomach or stomach-foodpipe junction cancer to prevent cancer from getting worse and live longer for at least 12 months

Phase 2
Not yet recruiting
Conditions
Malignant neoplasm of lower thirdof esophagus, (2) ICD-10 Condition: C169||Malignant neoplasm of stomach, unspecified,
Registration Number
CTRI/2025/06/088588
Lead Sponsor
Tata Memorial Hospital
Brief Summary

Title:- **Phase 2, randomized, investigator-initiated clinical study of Toripalimab plus chemotherapy versus placebo plus chemotherapy as first-line treatment in participants with HER2 negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (TORCH-GO)**

**Principle Investigator -** Dr Vikas S Ostwal:

**Study Site-** Tata Memorial Centre, Mumbai

**Summary**

The TORCH-GO study is a Phase 2, randomized, investigator-initiated, non-comparative clinical trial investigating the efficacy of Toripalimab combined with chemotherapy versus a placebo with chemotherapy as a first-line treatment for previously untreated HER2 negative, unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma.



The rationale for the study is supported by evidence showing improved outcomes in advanced cancers treated with immune checkpoint inhibitors like Toripalimab. The trial targets PD-L1 positive patients (CPS equal to or more than 10) and those with microsatellite instability-high (MSI-H) tumour status, hypothesizing that these groups are likely to benefit the most from the combination therapy.



The primary aim of the TORCH-GO study is to assess the efficacy of Toripalimab and chemotherapy versus a placebo combined with chemotherapy in terms of progression-free survival in patients with previously untreated HER2 negative, unresectable, or metastatic gastric or GEJ adenocarcinoma.



Inclusion criteria focus on participants with confirmed diagnoses, PD-L1 expression, HER2 negative status, and specific age and performance status benchmarks, while exclusion criteria highlight recent treatments, specific health conditions, and pregnancy

**Inclusion Criteria:** Participants must have a confirmed diagnosis of locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma, PD-L1 CPS more than or equal to 10, HER2 negative status, an ECOG performance status of 0 or 1, and measurable disease according to RECIST 1.1 criteria.

**Exclusion Criteria:** This includes prior treatment for the disease, certain health conditions, and significant recent surgeries or infections.

**Primary Objective**

**Progression-Free Survival (PFS)**: To assess the progression-free survival at 12 months in participants receiving Toripalimab plus chemotherapy versus those receiving a placebo plus chemotherapy.

Secondary Objectives

**Overall Survival (OS)**: To evaluate overall survival at 12 months.

**Objective Response Rate (OR)**: To determine the objective response rate at 6 months.

**Duration of Response (DOR)**: To assess the duration that patients maintain a response after treatment.

**Quality of Life (QoL)**: To evaluate the impact of the treatment on patients’ quality of life.

**Adverse Events (AEs)**: To monitor and record adverse events experienced by participants during the trial



**Study Design:** The trial is a Phase II, randomized, double-blinded study comparing Toripalimab plus CAPOX chemotherapy against a placebo plus CAPOX.



**Total Participants:** The study aims to enroll **190 patients,** with 95 in each arm over a span of two years for recruitment, followed by one year of follow-up.

**Treatment Arms:**Participants will be randomly assigned to one of two arms:

Arm A: Toripalimab plus CAPOX (capecitabine and oxaliplatin).

Arm B: Placebo plus CAPOX

**Randomization:** Patients are randomized in a 1:1 ratio while stratifying based on PD-L1 status and MSI status, ensuring balanced groups.

Treatment Administration

Group

**ARM A:-** Toripalimab dose 240 mg on Day 1 of each cycle Q3W given intravenouly

**ARM B:-** PlaceboDay 1 of each cycle Q3W administred intravenously with same method as Toripalimab

**Backbone Chemotherapy**

CAPOXOxaliplatin- dose 130 mg/m2 on Day 1 of each cycle Q3Wadministered intraveously with

capecitabine dose of 1000 mg/m2 twice daily on Days 1 to 14 of each cycle Q3W given orally



**Study Followups-**



**A. Safety Follow-up:**Timing: 30 days after the last dose of treatment.

Purpose: To monitor participants for any adverse events (AEs) following the end of their treatment regimen to ensure patient safety and assess any ongoing side effects related to the treatment.

 

**B.Efficacy Follow-up:**Timing: Every 9-12 weeks after the last dose of treatment.

Purpose: To evaluate the effectiveness of the treatment by assessing the participants’ response to therapy through regular imaging and clinical evaluations.

 

**C. Survival Follow-up:**Timing: Every 12 weeks through telephone contact.

Purpose: To gather information on overall survival and any changes in the participant’s health status, including disease progression or new treatment options post-trial.

 

**2. Imaging and Disease Status Assessment**

Participants who discontinue treatment for reasons other than progression of the disease will have post-treatment follow-up imaging conducted to monitor their disease status until any of the conditions for discontinuation are met.

 

**3. Duration of Follow-up**

Participants will continue to be followed for overall survival until one of the following conditions occurs:

·         The participant passes away.

·         The participant withdraws their consent to participate in the study.

·         The end of the study period.

 

**4. Additional Follow-up Procedures**

After achieving the study objectives, participants may be enrolled in extension studies to continue protocol-defined assessments and treatment, ensuring that data is gathered even after the main study is concluded.

Ethical considerations:-  General ethics for the conduct of the study- Study will be conducted in compliance with the ICMR Statement on Human Experimentation, and the Declaration of Helsinki principles. Declaration of Helsinki The trial will be performed in accordance with the Declaration of Helsinki, as decided upon by the 18th World Medical Assembly, Helsinki, Finland, June 1964 (amended by subsequent World  Medical Assembly Somerset West, South Africa, October 1996,).

Detailed Description

Not available

Recruitment & Eligibility

Status
Not Yet Recruiting
Sex
All
Target Recruitment
190
Inclusion Criteria
  • 1.Participants must be male or female and at least 18 years old when they provide documented informed consent.
  • Participants must have a histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, with known PD-L1 expression status.
  • PD-L1 CPS equal to or more than 10 and or MSI-H 4.Participants must have HER2 negative cancer, defined as IHC score of 0 or positive 1) or FISH negative (HER2 ratio less than 2 with an average HER2 copy number less than 4.0 signals per cell).
  • Locally available ISH methods may be used as per institutional guidelines.
  • Male participants must agree to refrain from donating sperm and either remain abstinent or use contraception during the study and for at least 95 days after the last dose of chemotherapy.
  • Female participants must not be pregnant or breastfeeding and must agree to use effective contraception if of childbearing potential (WOCBP), with pregnancy testing required before study participation.
  • Participants must provide written informed consent for the study, with optional consent for future biomedical research.
  • Participants must have measurable disease per RECIST 1.1 criteria as assessed by the investigator.
  • Participants must have an ECOG performance status of 0 or 1 within 3 days before starting the study intervention.
  • Participants must have adequate organ function as defined by study-specific laboratory criteria.
Exclusion Criteria
  • Participants with squamous cell or undifferentiated gastric cancer.
  • Participants who have had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or who anticipate needing major surgery during the study.
  • Participants must have recovered adequately from prior surgery.
  • Participants with preexisting peripheral neuropathy greater than Grade 1.
  • Women of childbearing potential (WOCBP) with a positive pregnancy test within 72 hours prior to randomization.
  • Participants with prior therapy for locally advanced, unresectable, or metastatic gastric/GEJ cancer, unless neoadjuvant/adjuvant therapy was completed at least 6 months before randomization.
  • Participants with prior anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy, or other T-cell receptor-targeting therapies (e.g., CTLA-4, OX-40, CD137).
  • Participants able to afford immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitors (Ipilimumab) as a standard of care will be excluded from the study.
  • Participants with prior systemic anticancer therapy within 4 weeks before randomization 9.
  • Participants with prior radiotherapy within 2 weeks before starting the study, unless it was used for palliative radiation to non-CNS disease.
  • Participants who have received a live or live-attenuated vaccine within 30 days before the first dose.
  • Participants currently in or recently participated in an interventional clinical study within 4 weeks prior to the first dose.
  • Participants with immunodeficiency or those receiving chronic systemic steroids (dose more than 10 mg prednisone equivalent) or immunosuppressive therapy within 7 days before the first dose.
  • Participants with a progressing malignancy or requiring active treatment within the past 5 years (except certain skin carcinomas or carcinoma in situ).
  • Participants with severe hypersensitivity (equal to or more than Grade 3) to Toripalimab or its excipients.
  • Participants with active autoimmune disease requiring systemic treatment in the past 2 years (except replacement therapy).
  • Participants with a history of (non-infectious) pneumonitis requiring steroids or current pneumonitis.
  • Participants with active infection requiring systemic therapy.
  • Participants with a known history of HIV infection.
  • Participants with a known history of active and uncontrolled Hepatitis B or C infection.
  • Participants with any condition or laboratory abnormality that might interfere with study results or participation.
  • Participants with a history of allogenic tissue/solid organ transplant.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)the time from the time of diagnosis of an advanced disease to the time of disease progression or loss to follow-up or death, whichever is earlier or at the end of 12 Months
Secondary Outcome Measures
NameTimeMethod
Overall survival (OS)defined as the time from the time of diagnosis to the time of death, lost to follow-up or last observation at the end of 12 Months
Objective response (OR)evaluated as per RECIST criteria at 6 months from the date of randomisation
side effects and adverse event profile with the combinationmeausered at the end of trial
quality of life assessmentat baseline and every two month till study participation

Trial Locations

Locations (1)

Tata Memorial Hospital, Mumbai

🇮🇳

Mumbai, MAHARASHTRA, India

Tata Memorial Hospital, Mumbai
🇮🇳Mumbai, MAHARASHTRA, India
Dr Vikas Ostwal
Principal investigator
9702288801
dr.vikas.ostwal@gmail.com

MedPath

Empowering clinical research with data-driven insights and AI-powered tools.

© 2025 MedPath, Inc. All rights reserved.