Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery

NCT04774419 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-491
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 7

Brief Summary

This study will test whether the combination of radiation and Dostarlimab is an effective treatment for women with MMR-D/MSI-H endometrial cancer who have recently undergone surgery.

Conditions

Endometrial Cancer

Keywords

Dostarlimab; Radiation; 20-491

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs) (Safety Run-in only)

  6-18 patients will be enrolled during a safety run-in period to assess toxicities. (NCI Common Terminology Criteria for Adverse Events version 5.0)

  up to 8 weeks

• Progression-free (PFS)

  PFS will be defined as the number of days from the date of the first dose of drug to the date of an event of disease progression/recurrence, according to RECIST criteria version 1.1

  2 years

Study Arms (2)

Radiation and Dostarlimab (THIS ARM IS COMPLETED)

EXPERIMENTAL

Patients will undergo standard intensity modulated radiation therapy (IMRT) to the pelvic nodes and vaginal cuff (total dose of 45-50.4Gy at 1.8 Gy per fraction) for 5-6 weeks and receive IV Dostarlimab every 3 weeks for 4 cycles followed by 1 dose of 1000mg (C5). Patients will receive a maximum of 5 cycles of Dostarlimab.

Radiation: Intensity modulated radiation therapy (IMRT); Drug: Dostarlimab

Hypofractionated IMRT and Dostarlimab

EXPERIMENTAL

Treatment will consist of short-course, hypofractionated IMRT to deliver 25 Gy to the vaginal cuff and pelvic lymph nodes in 5 daily fractions over one week. Participants will receive TSR-042 500mg every 3 weeks over 30 minutes for 4 cycles, followed by 1 dose of 1000mg for cycle 5. For this group, in those patients who have delays in C2 of dostarlimab and/or are unable to receive the 2nd dose of dostarlimab, hypofractionated radiation may proceed independently per discretion of treating investigator in consultation with study PI. Continuation of radiation therapy will be at the discretion of the radiation oncologist in discussion with study PI/co-PIs, and can be initiated/continued independent of dostarlimab dosing. Follow-up must continue regardless of radiation treatment received.

Drug: Dostarlimab; Radiation: Hypofractionated IMRT

Interventions

Intensity modulated radiation therapy (IMRT) RADIATION

To the pelvic nodes and vaginal cuff (total dose of 45-50.4Gy at 1.8 Gy per fraction) for 5-6 weeks.

Radiation and Dostarlimab (THIS ARM IS COMPLETED)

Dostarlimab DRUG

IV Dostarlimab every 3 weeks for 4 cycles followed by 1 dose of 1000mg (C5). Patients will receive a maximum of 5 cycles of Dostarlimab.

Also known as: TSR-042

Hypofractionated IMRT and Dostarlimab; Radiation and Dostarlimab (THIS ARM IS COMPLETED)

Hypofractionated IMRT RADIATION

Treatment will consist of short-course, hypofractionated IMRT to deliver 25 Gy to the vaginal cuff and pelvic lymph nodes in 5 daily fractions over one week.

Hypofractionated IMRT and Dostarlimab

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Endometrial Cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• ECOG performance status 0-1
• Endometrial cancer: all histologies (submission of pathology report is required for all patients who underwent surgery outside of MSK)
• MMR-D or MSI-H or POLE-mutated (submission of report\[s\] required for. patients who underwent testing outside of MSK POLE-mutated endometrial cancers will be included regardless of MMR/MSI status and limited to up to 3 patients per group.
• Patients with hypermethylation of MMR gene promoters (MLH1, MSH2, MSH6 or PMS2) will be included
• POLE-mutated endometrial cancers will be included
• Must have undergone a complete surgical staging and have stage III/IVA disease.
• Patients with measurable disease (RECIST 1.1) after surgery are NOT eligible.
• PatienSurgery completed between 3 weeks and 12 weeks (inclusive) before cycle 1 day 1 of therapy, and must have adequately recovered from surgery and any complications of surgery.ts with isolated tumor cells in lymph nodes found on surgery will be counted as clinical stage III disease
• Surgery completed between 3 weeks and 12 weeks (inclusive) before cycle 1 day 1 of therapy, and must have adequately recovered from surgery and any complications of surgery.
• Has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential, and agrees use an adequate method of contraception from screening through 150 days after the last dose of study treatment, or is of nonchildbearing potential. 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 an adequate birth control method throughout the study, starting with the screening visit through 150 days after the last dose of study treatment. See list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
• Participant must agree to not breastfeed during the study or for 150 days after the last dose of study treatment.

You may not qualify if:

• Has had prior chemotherapy, targeted therapy, or investigational therapy for endometrial cancer.
• °Patients who have received prior chemotherapy, targeted therapy, or other investigational therapies for other cancers and are in remission/cured may be included at the discretion of the treating investigator in consultation with the study PI.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 agent for endometrial cancer.
• Unfit for Radiation Therapy due to the following:
• Has had radiation therapy encompassing \>20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
• Patients with a prior history of pelvic radiation
• Patients with a prior known history or current diagnosis of a vesicovaginal, enterovaginal, or colovaginal fistula.
• Any hematological abnormality or disorder that would be a contraindication to radiation per the treating physician.
• Hypersensitivity to Dostarlimab or any of its excipients
• Patients with diagnosis of immunodeficiency or patients receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled.
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• Total systemic steroid dose cannot exceed an equivalent of 10mg of prednisone daily and dose must be stable for at least 4 weeks prior to initiating protocol therapy
• Has active TB (Bacillus tuberculosis)
• Has evidence of active, non-infectious pneumonitis.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Tesaro, Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activites)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack (All Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (All Protocol Activities)

Rockville Centre, New York, 11570, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; dostarlimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Ying Liu, MD, MPH

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Liu, MD, MPH

CONTACT

646-888-4946; liuy3@mskcc.org

Roisin O'Cearbhaill, MD

CONTACT

646-888-4227

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II stud y Adjuvant Checkpoint Blockade Plus Radiation in Locally Advanced, Mismatch Repair Deficient/Microsatellite Instability-High (MMR-D/MSIH) Endometrial Cancer with safety run-in of adjuvant checkpoint blockade with radiation in women with Stage III-IVA, dMMR/MSI-H endometrial cancer

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 1, 2021
• Study Start: April 2, 2021
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (7)