Neoplasms

All Conditions

Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Fluorouracil

Dostarlimab

Antimetabolites

Patients with clinical Stage II or Stage III MRI-staged, MSI-H or dMMR, solid tumors will receive up to 6 months (9, 21-day cycles) of PD-1 blockade followed by radiological and surgical restaging of the tumor. If subject exhibits complete clinical response, non-operative management will be followed. If a complete clinical response is not reached after 6 months of PD-1 blockade, the participant will proceed with standard chemoradiation. After completing chemoradiation participant will be assessed for response if complete CR is not obtained then the participant will proceed with disease specific surgical resection or standard of care therapy.

The plan is to enroll six patients with MSI, regardless of their primary cancer diagnosis. This cohort will serve to generate hypothesis and initial data to plan a larger study. All analyses from this cohort will be exploratory

Patients will be given TSR-042/Dostarlimab at a dose of 500mg IV, over 30 minutes Q 3 weeks.

TSR-042 or Dostarlimab

Capecitabine 825mg/m2 BID concurrently with radiation per standard radiation guidelines. If patient is unable to tolerate oral medication, infusional 5-FU is an acceptable alternative.

capecitabine or 5-FU

The radiation dose is 5400 cGy to the tumor and surrounding nodes 4700 cGy to the pelvis, with an integrated boost to the primary tumor and involved nodes of receiving 5400cGy in 27fx.

Intensity Modulated Radiation Therapy (IMRT)

Andrea Cercek, MD

Neil Segal, MD, PhD

Gerard Fumo, DO

Antonio Ucar, MD

Richard Zuniga, MD

Andera Cercek, MD

Leonard Saltz, MD

Maged Khalil, MD

The purpose of this study is to find out whether the study drug, TSR-042, followed by standard chemoradiotherapy (the chemotherapy drug capecitabine + radiation therapy) and standard surgery is an effective treatment for advanced dMMR solid tumors. The study will also look at the safety of the study drug.

This is a Phase II study investigating the efficacy of PD1 blockade with TSR-042 in patients with locally advanced MMRd or MSI rectal adenocarcinoma.

Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors

A Phase II Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

To determine the pathologic complete response rate (pCR) or complete clinical response (cCR) rate at 12 months, after PD-1 blockade and with or without chemoradiation in subjects with mismatch repair deficient locally advanced adenocarcinoma.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors	NCT04165772	Rectal Adenocar... Clinical Stage:... Stage III (Any ... Solid Tumor Solid Tumor, Ad...	TSR-042 or Dost... capecitabine or... Intensity Modul...	18 Years -	Memorial Sloan Kettering Cancer Center
Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors	NCT04165772	Rectal Adenocar... Clinical Stage:... Stage III (Any ... Solid Tumor Solid Tumor, Ad...	TSR-042 or Dost... capecitabine or... Intensity Modul...	18 Years -	Memorial Sloan Kettering Cancer Center
Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumors	NCT04165772	Rectal Adenocar... Clinical Stage:... Stage III (Any ... Solid Tumor Solid Tumor, Ad...	TSR-042 or Dost... capecitabine or... Intensity Modul...	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for stage iii (any t, n+)