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국부적으로 진행된 불일치 복구 결핍 고형 종양이 있는 피험자의 유도 PD-1 차단에 대한 연구

2026년 11월 2일 업데이트: Memorial Sloan Kettering Cancer Center

국부적으로 진행된 불일치 복구 결핍 고형 종양이 있는 피험자에서 PD-1 유도 차단에 대한 II상 연구

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.

연구 개요

상태

모병

정황

개입 / 치료

연구 유형

중재적

등록 (추정된)

212

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

  • 이름: Neil Segal, MD, PhD
  • 전화번호: 646-888-4187

연구 연락처 백업

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
의약품: TSR-042 or Dostarlimab

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

다른 이름들:
  • 도스타리맙
의약품: 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.

방사능: 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.
다른: 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
의약품: TSR-042 or Dostarlimab

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

다른 이름들:
  • 도스타리맙
다른: 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.
의약품: TSR-042 or Dostarlimab

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

다른 이름들:
  • 도스타리맙

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Pathologic complete response (pCR) or complete clinical response (cCR) at 12 months
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Memorial Sloan Kettering Cancer Center

협력자

Tesaro, Inc.

수사관

  • 수석 연구원: Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

유용한 링크

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2019년 12월 11일

기본 완료 (추정된)

2026년 11월 30일

연구 완료 (추정된)

2026년 11월 30일

연구 등록 날짜

최초 제출

2019년 11월 13일

QC 기준을 충족하는 최초 제출

2019년 11월 13일

처음 게시됨 (실제)

2019년 11월 18일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 11월 4일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 11월 2일

마지막으로 확인됨

2026년 10월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 19-288

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

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.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다