NCT06333314

Dostarlimab for Locally Advanced or Metastatic Cancer (Non-colorectal/Non-endometrial) With Tumor dMMR/MSI

Dostarlimab as First-line Treatment for Patients With dMMR/MSI (Non-colorectal/Non-endometrial) Locally Advanced or Metastatic Cancer: a Randomized Phase 2 Trial (Cohort Pan-MSI ACSE) With Crossover in the Standard Arm at Progression

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this open-label randomized, multicenter, comparative phase II trial is to evaluate the efficacy of the immunotherapy, dostarlimab, as first-line treatment for deficient mismatch repair (dMMR)/microsatellite instability (MSI) non-resectable metastatic or locally advanced non-colorectal and non-endometrial cancers compared to the standard of care chemotherapy. Adult patients (aged ≥18 years) with histologically confirmed dMMR/MSI duodenum and small bowel adenocarcinoma, gastric and oeso-gastric junction (OGJ) adenocarcinoma with combined positive score (CPS)\<5, pancreatic adenocarcinoma, ampulla of vater adenocarcinoma, adrenocortical carcinoma, carcinoma of unknown primary site, neuroendocrine carcinoma (Grade3) all primary, and soft tissue sarcoma (except Gastro-Intestinal Stromal Tumor) will be included in this study. They will be randomized and treated with either dostarlimab (experimental arm A), or chemotherapy (control arm B). Patients with documented disease progression following the first line chemotherapy (Arm B) may be eligible for crossover to be treated with dostarlimab, with the same schedule as arm A.

Detailed description

Following signature of the informed consent form, patients will enter the pre-inclusion period (maximum 28 days prior to start of treatment) during which all examinations required to assess their eligibility will be performed, including dMMR/MSI status, demographic data collection, tumor evaluation, and clinical and laboratory evaluations. A centralized confirmation of MMR/MSI status by immunohistochemistry (IHC) or next-generation sequencing (NGS)/polymerase chain reaction (PCR) is mandatory to include the patient. Patients will be randomized 1:1 to receive either dostarlimab intravenously 500 mg every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks for all cycles thereafter (experimental arm A) or chemotherapy (control arm B) as per standard of care (SOC) until disease progression, unacceptable toxicity, death, investigator's decision, withdrawal of consent or for a maximum of 24 months. Randomization will be stratified by: * Primary tumor (Duodenum and Small Bowel/Gastric/OGJ vs Pancreas/ Ampulla of Vater vs Other), * Age (\<70 years vs ≥70 years) * Stage: Locally advanced vs Metastatic. Patients randomized to Arm B may be eligible to participate in the crossover phase after documentation of disease progression by investigator evaluation according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Crossover patients may then be treated with dostarlimab for up to 2 years, according to the schedule defined for experimental arm A. These patients may not initiate treatment with dostarlimab any earlier than 28 days after their last dose of chemotherapy (washout period) regardless of the time of progression. Patients who discontinue dostarlimab treatment after crossover will enter the follow-up phase until the last follow-up visit of the last randomized patient. Crossover is optional and is at the discretion of the investigator (with coordinating investigator's agreement). In both arms, tumor evaluation will be done by local investigator at inclusion and post-randomization visits as follow: * Treatment period: every 6 weeks (+/- 7 days) for the first year then every 12 weeks (+/- 7 days) for the second year. * Follow-up period: every 16 weeks (+/- 7 days) up to one year after the last follow-up of the last randomized patient.

Conditions

• Pancreatic Adenocarcinoma
• Ampulla of Vater Carcinoma
• Adrenocortical Carcinoma
• Neuroendocrine Carcinoma
• Soft Tissue Sarcoma
• Small Bowel Adenocarcinoma
• Duodenum Adenocarcinoma
• Gastric Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Dostarlimab	Anti-PD-1 monoclonal antibody
DRUG	Chemotherapy	* mFOLFOX6 or FOLFIRI or XELOX regimen * FOLFOX or XELOX or TFOX regimen * FOLFIRINOX or gemcitabine-nab-paclitaxel or gemcitabine monotherapy. * Cisplatin and gemcitabine cisplatin or CAPOX or mFOLFOX6. * Etoposide-cisplatin-doxorubicin or mitotane * Cisplatin and gemcitabine or carboplatin and paclitaxel * Etoposide-cisplatin or etoposide-carboplatin * Doxorubicin and ifosfamide or doxorubicin monotherapy or doxorubicin and trabectedin.

Timeline

• Start date: 2024-07-23
• Primary completion: 2028-10-01
• Completion: 2030-09-01
• First posted: 2024-03-27
• Last updated: 2025-12-02

Locations

22 sites across 1 country: France