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.
Capable of giving signed and dated informed consent,
An ECOG PS of 0-1,
≥18 and ≤75 years old,
The patient's G8 questionnaire score is above 14 AND
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,
Single group
Dostarlimab
DrugAfter 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)
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.
Pathological complete response (pCR)
Pathological complete response is defined as 100% fibrosis or fibro-inflammation or necrosis or granulomatous reaction within an entire gross lesion without microscopic evidence of carcinoma, and no positive lymph nodes, after examination of the complete macroscopic surgical specimen equivalent to a Becker TRG Grade 1a (complete regression).
Loco/loco-regional and distant recurrence
Loco/loco-regional recurrence is defined as cancer recurrence within the regional resection area or local anastomotic site. Distant recurrence is defined as peritoneal recurrence, liver metastasis or metastasis at other extra-abdominal sites as well as nodal metastasis beyond the regional nodes
Event-free survival (EFS)
Event-free survival is defined as time from first dose of treatment to surgery for tumoral resection, first progression of disease local or distant recurrence, or death due to any cause. Alive patients without event will be censored at the last follow-up.
Time to treatment failure (TTF)
Time to treatment failure is defined as the interval between initiating therapy (first dose of dostarlimab) and the earliest of clinical progression, depending on whether the patient had surgery for tumoral resection or no, or death.
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