A Study of the Duration of Dostarlimab in Untreated Mismatch Repair Deficient (dMMR)/ Microsatellite Instability-high (MSI-H) Locally Advanced Rectal Cancer (DuraSTAR)

A Phase 3b, Open-label Study Investigating the Duration of Neoadjuvant Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer

This study is conducted in adults with rectal cancer that has a certain genetic type. The main goal is to find out whether a longer treatment period with dostarlimab can help more participants have a complete response to treatment and avoid standard treatments like chemotherapy, radiation treatment, or surgery. Scans and endoscopy tests will be conducted to see if the tumor disappears and how long the cancer stays under control. The study will also collect information on side effects and health outcomes after dostarlimab.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoplasms, Rectal
• Intervention / Treatment: Biological: Dostarlimab

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+) locally advanced rectal adenocarcinoma.
• Has radiologically and endoscopically evaluable disease.

• Has a tumor demonstrating the presence of either:

  1. dMMR status; MMR status must be assessed by immunohistochemistry for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of 1 or more proteins indicates dMMR; MMR status will be determined locally; or
  2. MSI-H phenotype as determined by polymerase chain reaction or by tissue next generation sequencing; MSI-H will be determined locally.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function.

Exclusion Criteria:

• Has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer.
• Has a tumor that, in the investigator's judgment, is causing symptomatic bowel obstruction or otherwise requires urgent/emergent local intervention. Participants with a history of bowel obstruction are eligible after obstruction is relieved by a diverting stoma (defunctioning colostomy). Patients with a history of bowel obstruction in the context of current rectal cancer diagnosis and treated with stenting are not eligible.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury within 28 days prior to enrollment.
• Is receiving any other anticancer or experimental therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dostarlimab	Biological: Dostarlimab; Dostarlimab will be administered.; Other Names: GSK4057190, dostarlimab-gxly, TSR-042

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants who achieve clinical complete response (cCR) amongst participants who receive > 9 cycles (> 6 months) of dostarlimab monotherapy by investigator assessment	Up to 168 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall cCR rate by investigator assessment	Overall cCR rate is defined as the percentage of participants achieving cCR by investigator assessment at any disease assessment, regardless of duration of dostarlimab therapy among all enrolled participants.	Up to 171 weeks
Number of participants with sustained clinical complete response at 12 months (cCR12) as assessed by investigator	cCR12 is defined as achievement and maintenance of cCR for 12 months from the disease assessment after the last dose of study intervention that first demonstrates cCR by investigator assessment.	Up to 171 weeks
Objective response rate (ORR) as assessed by investigator	ORR is defined as the percentage of participants who achieve a best clinical response of partial response (PR), near complete response (nCR), or clinical complete response (cCR) at any disease assessment.	Up to 171 weeks
Number of participants with composite cCR12 and pathologic complete response (pCR) as assessed by investigator	The composite endpoint of cCR12 and pCR is defined as the number of participants who either achieve cCR12, or achieve pCR after receiving dostarlimab (before receiving standard of care)	Up to 171 weeks
Time to cCR	Time to cCR is defined as the time from the first dose of study intervention to the time of first cCR as assessed by the investigator.	Up to 171 weeks
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), immune-mediated adverse event (imAEs), and AEs leading to death or discontinuation of study intervention by severity		Up to 171 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): September 17, 2026
• Primary Completion (Estimated): December 12, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: July 24, 2026
• First Submitted That Met QC Criteria: July 24, 2026
• First Posted (Actual): August 3, 2026

Study Record Updates

• Last Update Posted (Actual): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 24, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Locally advanced rectal cancer; PD-1; Anti-PD1; LARC; Dostarlimab; dMMR; MSI-H; GSK4057190; DuraSTAR
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; dostarlimab
• Other Study ID Numbers: 308360; 2026-526683-21 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No