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

May 8, 2026 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

212

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Neil Segal, MD, PhD
  • Phone Number: 646-888-4187

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Recruiting
        • Hartford Healthcare (Data Collection)
        • Contact:
          • Gerard Fumo, DO
          • Phone Number: 860-972-4700
    • Florida
      • Miami, Florida, United States, 33143
        • Recruiting
        • Baptist Alliance MCI (Data Collection Only)
        • Contact:
          • Antonio Ucar, MD
          • Phone Number: 786-373-3436
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge - Limited Protocol Activities
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
        • Principal Investigator:
          • Andrea Cercek, MD
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth - Limited Protocol Activities
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen - Limited Protocol Activities
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack - Limited Protocol Activities
        • Principal Investigator:
          • Andera Cercek, MD
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester - Limited Protocol Activities
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Leonard Saltz, MD
          • Phone Number: 646-888-4181
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
        • Principal Investigator:
          • Andrea Cercek, MD
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau - Limited Protocol Activities
        • Contact:
          • Andrea Cercek, MD
          • Phone Number: 646-888-4189
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Recruiting
        • Lehigh Valley Health Network (Data Collection Only)
        • Contact:
          • Maged Khalil, MD
          • Phone Number: 610-402-7880

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Willing and able to provide written informed consent for the trial.
  • Be ≥18 years of age on the date of signing informed consent.
  • ECOG performance status of 0 or 1.
  • Histologically confirmed locally advanced solid tumor (Cohorts 1 & 2)
  • Histologically confirmed endometrial cancer (Cohort 3)
  • Solid tumors that in standard practice would be treated with neoadjuvant therapy or surgery (depending on tumor type) (Cohorts 1 & 2)
  • Endometrial cancer that is clinically FIGO 2009 Stage I or II (Cohort 3).

  • No evidence of distant metastases.

    • Radiologically measurable or clinically evaluable disease
  • Tumor specimen that demonstrates mismatch repair deficiency by Immunohistochemistry or microsatellite instability as demonstrated by NGS or PCR.

  • Negative pregnancy test done 72 hours prior to beginning treatment, for women of childbearing potential only. Subjects of childbearing potential must be willing to use an adequate method of contraception. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom). Contraception, for the course of the study starting with the first dose of study medication through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

    1. For Cohort 3, the use of a combination estrogen/progesterone contraceptive is allowed; the use of progesterone-only methods including hormone (progestin) releasing IUD, depot medroxyprogesterone acetate, and progestin-only birth control pills is not allowed.

Nonchildbearing potential is defined as follows (by other than medical reasons):

  • ≥45 years of age and has not had menses for >1 year
  • Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation

  • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study.

    • Participant receiving corticosteroids may continue if their dose is stable for least 4 weeks prior to initiating protocol therapy.
    • Has QTcF ≤ 450 msec, or ≤ 480 msec for participants with bundle branch block.
    • Demonstrate adequate organ function as defined below within 14 days of Cycle 1, Day 1, all screening labs should be performed within 14 days of treatment initiation.
    • Hematological
  • Absolute neutrophil count (ANC) ≥1,500 /mcL
  • Platelets ≥100,000 / mcL

  • Hemoglobin >9 g/dL or ≥5.6 mmol/L

    • Renal

  • Serum creatinine OR Measured or calculated(a) creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 × institutional ULN

    • Hepatic
  • Serum total bilirubin ≤ 1.5 × ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN

  • AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN

    • Coagulation
  • International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended (a) Creatinine clearance should be calculated per institutional standard.

Exclusion Criteria:

  • Presence of metastatic or recurrent disease

  • Prior radiation therapy, chemotherapy, or surgery for tumor

    a. NOTE: For Cohort 3, patients are allowed to have received prior hormonal therapy for treatment of endometrial hyperplasia and/or endometrial cancer. Hormonal therapy must be discontinued at least 1-week prior to first dose of study treatment (dostarlimab).

  • For patients with colorectal primary -Tumor is causing symptomatic bowel obstruction (patients who have a temporary diverting ostomy are eligible).
  • Cohort 1 Only: Other invasive malignancy ≤ 5 years prior to registration. Exceptions are non-melanoma skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma.
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of non- physiologic dose immunosuppressive therapy within 7 days prior to first dose of trial treatment.
  • Active autoimmune disease requiring systemic treatment within the past 2 years or documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents at non-physiologic doses.
  • Active infection requiring systemic therapy.
  • Cohort 1 & 3: Received prior therapy with an antibody or drug specifically targeting T- cell co-stimulation or checkpoint pathways.
  • Experienced ≥ Grade 3 immune-related AE with prior immunotherapy, except for non-clinically significant lab abnormalities.
  • Other Anticancer or Experimental Therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
  • Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Women who are pregnant or breastfeeding, or men expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening visit through 150 days after the last dose of study medication.
  • Concurrent medical or psychiatric condition or disease which, in the investigator's judgement, would make them inappropriate candidates for entry into the study. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
  • Received a live vaccine within 30 days of planned start of study medication.

  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment.

    a. NOTE: For Cohort 3: endometrial sampling (e.g., biopsies, dilatation and curettage), is NOT considered major surgical procedure.

  • History of interstitial lung disease.
  • Known hypersensitivity to TSR-042 components or excipients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
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.
Drug: TSR-042 or Dostarlimab
Patients will be given TSR-042/Dostarlimab at a dose of 500mg IV, over 30 minutes Q 3 weeks.
Other Names:
  • Dostarlimab
Drug: capecitabine or 5-FU
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.
Radiation: Intensity Modulated Radiation Therapy (IMRT)
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.
Other: Cohort 2
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
Drug: TSR-042 or Dostarlimab
Patients will be given TSR-042/Dostarlimab at a dose of 500mg IV, over 30 minutes Q 3 weeks.
Other Names:
  • Dostarlimab
Other: Cohort 3
Participants with FIGO Stage I or II mismatch repair deficient (MMRd) and/or microsatellite instability high (MSI-H) endometrial cancer will receive intravenous dostarlimab.
Drug: TSR-042 or Dostarlimab
Patients will be given TSR-042/Dostarlimab at a dose of 500mg IV, over 30 minutes Q 3 weeks.
Other Names:
  • Dostarlimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic complete response (pCR) or complete clinical response (cCR) at 12 months
Time Frame: 12 months
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Tesaro, Inc.

Investigators

  • Principal Investigator: Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 11, 2019

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

November 30, 2026

Study Registration Dates

First Submitted

November 13, 2019

First Submitted That Met QC Criteria

November 13, 2019

First Posted (Actual)

November 18, 2019

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-288

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Solid Tumor

Clinical Trials on TSR-042 or Dostarlimab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Benin

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe