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

NCT06333314 | Recruiting Phase 2

• 1 other identifier: UC-IMM-2302
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 22

Brief 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.

Conditions

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

Keywords

Immunotherapy; locally advanced or metastatic cancer; dMMR/MSI (non-colorectal/non-endometrial) cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

  From randomization until disease progression or death from any cause, up to 3 years.

Secondary Outcomes (9)

• Objective Response Rate

  From randomization to disease progression or death, up to 3 years

• Duration of response

  From randomization to disease progression or death, up to 3 years

• Overall Survival

  From randomization until death from any cause, up to 3 years

• Progression-Free Survival 2

  From randomization to disease progression or death, up to 3 years

• Objective response rate 2

  From randomization to disease progression or death, up to 3 years

Study Arms (2)

Dostarlimab

EXPERIMENTAL

Patient will receive dostarlimab intravenously 500 mg every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks for all cycles thereafter until disease progression, unacceptable toxicity, death, investigator's decision, patient's decision or for a maximum of 24 months.

Drug: Dostarlimab

Standard of care

ACTIVE COMPARATOR

Patients will receive the standard of care chemotherapy

Drug: Chemotherapy

Interventions

Dostarlimab DRUG

Anti-PD-1 monoclonal antibody

Dostarlimab

Chemotherapy DRUG

* 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.

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have signed a written informed consent form prior any trial specific procedures. -
• years or older patients.
• Documented locally advanced or metastatic disease with no previous systemic anti-cancer treatment in these settings and not suitable for complete surgical resection.
• Histologically proven, dMMR/MSI-H solid tumors that are not colorectal or endometrial cancers and including one of the following: duodenum and small bowel adenocarcinoma, gastric and oeso-gastric junction adenocarcinoma with CPS\<5, pancreatic adenocarcinoma, ampulla of Vater adenocarcinoma, adrenocortical carcinoma, carcinoma of unknown primary site, neuroendocrine carcinoma (Grade 3) all primary, and soft tissue sarcoma except Gastro-Intestinal Stromal Tumor (GIST).
• If patient received adjuvant therapy for non-metastatic disease, this therapy should be completed more than 6 months before the diagnosis of metastatic or recurrent disease.
• Availability of minimum 1 block of tumor tissue or 20 slides (archival (\<2 years) or fresh biopsy specimen of primary and or metastasis) for centralized confirmation of MMR/MSI status by IHC or NGS/PCR, and for Translational Research.
• Patients with dMMR/MSI tumor analyzed by IHC, PCR (for Gastric and OGJ adenocarcinoma, and duodenum and small bowel adenocarcinoma only), and/or NGS at the recruiting center should be confirmed by central review within 24h (every anonymized patient analysis reporting will be provided for central review). Patients should not be included in the study until the dMMR/MSI status is confirmed by the review committee.
• Presence of at least one measurable lesion within 28 days before the start of treatment according to RECIST v1.1.
• Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1.
• Haematological status: absolute neutrophil count (ANC) ≥1.5 x 10⁹/L; platelets ≥100 x 10⁹/L; haemoglobin ≥9 g/dL.
• Adequate renal function: serum creatinine level \<120 µM, or clearance \>50 ml/min (Modification of the Diet in Renal Disease \[MDRD\] or Cockcroft and Gault).
• Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, unless liver metastases are present, in which case they must be ≤ 5× ULN.
• For patients not taking warfarin: International normalised ratio (INR) \<1.5 or prothrombin time (PT) \<1.5 x ULN and either partial thromboplastin time (PTT) or activated PTT (aPTT) \<1.5 x ULN. Participants taking warfarin may be included on a stable dose with a therapeutic INR \<3.5.
• Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours before the date of randomization.
• Men, and women of childbearing potential must agree to use adequate contraception for the duration of trial participation and for 4 months after the last dose of dostarlimab (used in first line or at crossover) or for at least 6 months after the last administration of the chemotherapy agent(s) used in the control arm if no crossover with dostarlimab (according to the current version of the summary of product characteristics (SmPC) of each chemotherapy agent). Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.

You may not qualify if:

• Previous exposure to anti-PD-1 or PD-L1 or anti-CTL-4 antibodies or treatment with immunotherapy.
• Previous exposure to any investigational drug within 4 weeks (6 weeks for monoclonal antibodies) before the first dose in the study.
• Previous exposure to any systemic anti-cancer therapy or radiation therapy for the cancer for which the patient is being enrolled.
• Active autoimmune disease: Active autoimmune disease requiring systemic treatment in the past 2 years (excluding replacement therapy) or any history of interstitial lung disease (patients with ancient auto-immune disease with stable endocrine oral substitution are eligible).
• Uncontrolled central nervous system metastases or carcinomatous meningitis or other concurrent illness or ongoing or active infections.
• Patients with HER2-positive gastric carcinoma.
• Other serious and uncontrolled non-malignant disease or is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Has received treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to the first dose of adjuvant treatment or is required to receive systemic immunosuppressive medications during the study. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Note 1: Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled into the study after approval of the Medical Contact.
• Note 2: patients are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses including doses \>10 mg daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is permitted.
• Other concomitant or previous malignancy other than the disease under study, except as noted below:
• i. adequately treated in-situ carcinoma of the uterine cervix, ii. basal or squamous cell carcinoma of the skin, iii. cancer from which the patients was in complete remission for \>2 years.
• Known Human Immunodeficiency Virus (HIV) infection.
• Received live vaccine within 14 days.

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator
• GlaxoSmithKline: collaborator

Study Sites (22)

Institut de Cancérologie de l'Ouest

Angers, France

NOT YET RECRUITING

Institut du Cancer Avignon-Provence

Avignon, France

NOT YET RECRUITING

CHU Jean Minjoz

Besançon, France

NOT YET RECRUITING

CHU Morvan

Brest, France

NOT YET RECRUITING

Centre François Baclesse

Caen, France

NOT YET RECRUITING

Centre Jean Perrin

Clermont-Ferrand, France

NOT YET RECRUITING

CHU - Henri Mondor

Créteil, France

NOT YET RECRUITING

Centre Georges François Leclerc

Dijon, France

NOT YET RECRUITING

Centre Léon Bérard

Lyon, France

RECRUITING

Hôpital la Timone

Marseille, France

NOT YET RECRUITING

Institut Paoli Calmettes

Marseille, France

NOT YET RECRUITING

Institut de Cancérologie de Lorraine

Nancy, France

NOT YET RECRUITING

Institut Mutualiste Montsouris

Paris, France

NOT YET RECRUITING

CHU de Bordeaux - Hôpital Haut -Lèvêque

Pessac, France

NOT YET RECRUITING

CHU de Poitiers

Poitiers, France

NOT YET RECRUITING

Institut Jean Godinot

Reims, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, France

NOT YET RECRUITING

CHU de Rouen

Rouen, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

NOT YET RECRUITING

CHU de Toulouse Hôpital Rangueil

Toulouse, France

NOT YET RECRUITING

Gustave Roussy Grand Paris

Villejuif, France

NOT YET RECRUITING

Hôpital Saint-Antoine

Paris, Île-de-France Region, France

NOT YET RECRUITING

MeSH Terms

Conditions

Adrenocortical Carcinoma; Carcinoma, Neuroendocrine; Sarcoma; Neoplasm Metastasis; Neoplasms

Interventions

dostarlimab; Drug Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Connective and Soft Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Thierry ANDRE, MD

  Hôpital Sainte Antoine - Paris - France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Assia LAMRANI-GHAOUTI

CONTACT

+33 (0) 6 16 73 01 54; a-lamrani-ghaouti@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, multicenter, comparative phase II trial

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: March 27, 2024
• Study Start: July 23, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): September 1, 2030
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (22)