Watch-and-Wait Approach With Dostarlimab in Localized dMMR/MSI-H Gastric Cancer: GERCOR Phase II Study

NCT06059495 | Recruiting Phase 2

• 2 other identifiers: DEWI G-1232023-506102-39-00
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II study will evaluate dostarlimab with a watch-and-wait approach for patients with localized mismatch repair deficiency (dMMR)/microsatellite instability (MSI) gastric or oeso-gastric junction adenocarcinoma. The goal of the study is to determine whether the surgery could be avoided in patients with localized dMMR/MSI-H gastric/OGJ adenocarcinoma with complete response at endoscopy and biopsies free of tumoral cells after treatment with dostarlimab, with a watch-and-wait approaches.

Conditions

Adenocarcinoma - GEJ; Gastric Adenocarcinoma

Keywords

dMMR; MSI-H; dostarlimab; watch-and-wait; surgery; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Clinical complete response (cCR)

  The primary endpoint is the rate of patients who at 1 year from the start of therapy with dostarlimab are alive, were not operated for tumor resection, are free of disease progression (locoregional or metastases), have all biopsies negative, and show endoscopy downstaging stage 3 and 4.

  From the start of therapy with dostarlimab to 1 year; assessed at 1 year.

Secondary Outcomes (6)

• Pathological complete response (pCR)

  up to 5 years; from the date of dostarlimab initiation to the date of surgery

• Loco/loco-regional and distant recurrence

  up to 5 years; from the date of dostarlimab initiation to the date of recurrence

• Event-free survival (EFS)

  up to 5 years; from the date of dostarlimab initiation to the date of surgery

• Time to treatment failure (TTF)

  up to 5 years; from the date of dostarlimab initiation to the date of progression or death

• Disease-free survival (DFS)

  up to 5 years; from the date of surgery to the date of recurrence or death from any cause

Study Arms (1)

Dostarlimab-based treatment

EXPERIMENTAL

After inclusion patients will receive dostarlimab at 500 mg q3w (± 2-3 days) for 4 cycles (C1-C4). Then, an adaptive treatment strategy will be determined based on clinical assessment of the patient.

Drug: Dostarlimab

Interventions

Dostarlimab DRUG

After inclusion: dostarlimab 500mg IV 30min q3w (± 2-3 days) for 4 cycles (C1-C4) Then: At wk12 • If cCR: dostarlimab 1000mg q6w for 2 cycles (C5-C6) • If downstaging at UGI endoscopy, and no disease progression (PD)/or mets on TAP-CT, \<3 biopsies with tumor cells: dostarlimab 500mg q3w for 4 cycles (C5-C8) • If loco/loco-regional PD on TAP-CT, macroscopic tumor on UGI endoscopy, no distant mets, and \>2 positive biopsies at wk12 followed by surgery and if Becker-TRG 1a, 1b, or 2 after surgery: dostarlimab 1000mg q6w for 6 cycles (C5-C10) At 24wk • If cCR at 12 and 24 wks: dostarlimab 1000mg q6w for 4 cycles (C7-C10) • If downstaging at UGI endoscopy without PD on CT at wk 12 with \<3 biopsies with tumor cells at wk12 and cCR: dostarlimab 1000mg q6w for 4 cycles (C9-C12) • If downstaging at UGI endoscopy without PD on CT at wk 12 with and no cCR, surgery will be proposed and if Becker-TRG 1a, 1b, or 2 after surgery: dostarlimab 1000mg q6w for 4 cycles (C9-C12)

Also known as: Jemperli

Dostarlimab-based treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed and dated informed consent,
• An ECOG PS of 0-1,
• ≥18 and ≤75 years old,
• The patient over 75 years of age is eligible only if all the following conditions are met:
• The patient's G8 questionnaire score is above 14 AND
• The patient is eligible for surgery and has no contraindications to repeated UGI endoscopy with biopsies,
• Histologically proven non-metastatic gastric or OGJ adenocarcinoma cT2 to T4, Nx, M0 after computed tomography thorax-abdomen-pelvis (TAP-CT) and echo-endoscopy (EUS) according to the 7th Edition of the International Union Against Cancer; NB: Echo-endoscopy will be performed only if the tumor is not obstructive at UGI endoscopy ± a new UGI endoscopy with 10 biopsies, photos (if not done at the first UGI endoscopy done for diagnosis) and if possible (not mandatory) tumor tattooing/inking. If obstructive, the tumor will be classified as cT3 or cT4 (in the situation when the tumor was obstructive and prevented EUS, it was classified T3N+, if it did not invade the adjacent organs on CT scan, because obstructing tumours represented locally advanced disease in the vast majority of cases in previous studies). In this case a new UGI endoscopy must be done with 10 biopsies, photos (if not done at the first GGI endoscopy done for diagnosis) and if possible (not mandatory) tumor tattooing/inking to follow the location of the tumor.
• No peritoneal carcinomatosis (optional coelioscopy; recommended in case of doubt/ suspicious on CT/ imaging),
• No prior therapy (chemotherapy, radiotherapy, or immunotherapy) for localized gastric or OGJ adenocarcinoma,
• Tumor status confirmed to be dMMR/MSI-H as follows:
• \- MMR protein expression status will be evaluated by immunohistochemistry (IHC) with four antibodies (anti-hMLH1, anti-hMSH2, anti-hMSH6, anti-hPMS2) according to the local procedures. dMMR will be defined as loss of MLSH1 and PMS2, loss of MSH2 and MSH6, or loss of only one protein with presence of MSI-H.
• Hematological status: absolute neutrophil count (ANC) ≥1.5 x 109/L; platelets ≥100 x 109/L; hemoglobin ≥9 g/dL,
• Adequate renal function: serum creatinine level ≤150 μM and clearance ≥50 ml/min (Modification of the Diet in Renal Disease \[MDRD\] or Cockcroft and Gault),
• International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5 x ULN, except for the patient on anticoagulant therapy who must have PT-INR-aPTT within therapeutic range is deemed appropriate by the Investigator,
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:

You may not qualify if:

• Prior concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, immunotherapy),
• Treatment with any investigational medicinal product within 28 days prior to study entry,
• Treatment anticoagulant or hemostasis disorder contraindicating - biopsies during endoscopy,
• Major surgical procedure within 28 days (4 weeks) prior to the first dose of study treatment,
• Other serious and uncontrolled non-malignant disease (including active infection) or is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant 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,
• 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 ≥3 years,
• Metastases (M stage disease) whatever the location,
• Pregnancy or breastfeeding,
• Human immunodeficiency virus (HIV),
• Note: Patients positive for HCV antibody are eligible only if PCR testing is negative for HCV RNA.
• Patient under a legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapable of giving his/her consent,
• Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness.
• Non-eligible to immunotherapy:
• Pyloric tumor, NB: tumors of the pylorus will be excluded because of the risk of high occlusion in case of pseudo progression and associated surgery,

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead

Study Sites (2)

CHRU Lille

Lille, France

RECRUITING

Hôpital Saint Antoine

Paris, France

RECRUITING

MeSH Terms

Interventions

dostarlimab

Study Officials

• Thierry Andre, MD

  Saint-Antoine Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Line GARCIA LARNICOL, MD

CONTACT

+33 (01) 40 20 85 00; gercor@gercor.com.fr

Study Design

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

Model Details: After inclusion all patients will receive dostarlimab at 500 mg q3w (± 2-3 days) for 4 cycles (C1-C4). An adaptive treatment strategy will be determined based on clinical assessment of the patient at weeks 12 (±1 week) and week 24 (±1 week).

Study Record Dates

• First Submitted: July 20, 2023
• First Posted: September 28, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: February 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)