116TiP - An umbrella trial (RECHALLENGE) to evaluate the safety and preliminary efficacy of combination or sequential immunotherapy in advanced solid tumor patients after disease progression in clinical trials

Background

Immune checkpoint inhibitors (ICIs) are now standard for many tumors, but many patients don't respond or develop resistance. Consequently, novel immunotherapeutic drugs are in clinical trials, showing promise for synergy with ICIs. This umbrella trial will evaluate the safety and preliminary efficacy of combination or sequential immunotherapy in advanced solid tumors after progression in clinical trials.

Trial Design

This study aims to enroll 100 patients with advanced solid tumors who have progressed after clinical trial treatments. It uses an open-label, single-arm, multi-cohort umbrella design. Participants will receive Triplimab in either combination or sequential regimens. Selection focuses on phase I trials of novel immunotherapies, including tumor vaccines, cell therapy, and innovative ICIs. The trial will have cohorts for combination therapy, sequential therapy, and real-world scenarios. In the combination therapy cohort, patients will be stratified based on their initial investigational drug. Those who progressed on drug A (SG1827, CD80 fusion protein) or B (ABO2011, mRNA vaccine encoding IL-12) will receive their respective drug with Triplimab at 3 mg/kg IV every two weeks, continuing their prior treatment regimen (cohort A, B). More cohorts will open in the future. The sequential therapy cohort will uniformly receive Triplimab regardless of frontline trial drugs. The real-world cohort includes patients who don't meet the interventional criteria or opt out, with only data collection. Key eligibility criteria are advanced solid tumors, progression after first-line clinical trials, and no longer benefiting from initial treatment. Exclusion criteria include serious immune-related adverse events or tumor hyperprogression after prior immunotherapy. The primary endpoint is safety and tolerability, with adverse events graded by CTCAE v5.0. Secondary endpoints include efficacy assessments like objective response rate, disease control rate, duration of response, progression-free survival, and overall survival. This trial began in May 2024 and has enrolled 3 patients at the time of submission.

Clinical trial identification

NCT06612632.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.