A Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1)

A Phase 2, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer

The purpose of this study is to investigate dostarlimab monotherapy in participants with locally advanced Mismatch-repair deficient (dMMR)/Microsatellite instability-high (MSI-H) rectal cancer who have received no prior treatment. Participants who achieve complete clinical response (cCR) following dostarlimab treatment will undergo non-operative management (NOM), including close surveillance for recurrent disease. The goal of the study is to determine if Dostarlimab therapy alone is an effective treatment that can allow participants to avoid chemotherapy, radiation, and surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasms, Rectal
• Intervention / Treatment: Biological: Dostarlimab

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C1
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • GSK Investigational Site
• France
  • Besançon, France, 25030
    • GSK Investigational Site
  • Marseille, France, 13273
    • GSK Investigational Site
  • Paris, France, 75012
    • GSK Investigational Site
  • Pessac, France, 33604
    • GSK Investigational Site
  • Rennes, France, 35000
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 13353
    • GSK Investigational Site
  • Dresden, Germany, 01307
    • GSK Investigational Site
  • Düsseldorf, Germany, 40225
    • GSK Investigational Site
  • Frankfurt, Germany, 60488
    • GSK Investigational Site
  • München, Germany, 81377
    • GSK Investigational Site
• Italy
  • Milan, Italy, 20133
    • GSK Investigational Site
  • Padua, Italy, 35128
    • GSK Investigational Site
  • Roma, Italy, 00168
    • GSK Investigational Site
• Japan
  • Chiba, Japan, 277-8577
    • GSK Investigational Site
  • Kanagawa, Japan, 232-0024
    • GSK Investigational Site
  • Osaka, Japan, 540-0006
    • GSK Investigational Site
  • Osaka, Japan, 565-0871
    • GSK Investigational Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • GSK Investigational Site
• South Korea
  • Seoul, South Korea, 06591
    • GSK Investigational Site
  • Seoul, South Korea, 05505
    • GSK Investigational Site
  • Seoul, South Korea, 120-752
    • GSK Investigational Site
  • Seoul, South Korea, 135-710
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Granada, Spain, 18014
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Madrid, Spain, 28007
    • GSK Investigational Site
  • Santander, Spain, 39008
    • GSK Investigational Site
  • Valencia, Spain, 46010
    • GSK Investigational Site
• United Kingdom
  • Leeds West Yorkshire, United Kingdom, LS9 7TF
    • GSK Investigational Site
  • London, United Kingdom, EC1A 7BE
    • GSK Investigational Site
  • Sutton, United Kingdom, SM2 5PT
    • GSK Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90027
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10022
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • GSK Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75390
      • GSK Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+), locally advanced rectal cancer
• Participant has radiologically and endoscopically evaluable disease.
• Participant has a tumor which can be categorized as dMMR or MSI-H by local or central assessment

Exclusion Criteria:

• Participant has distant metastatic disease.
• Participant has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer.
• Participant has any history of interstitial lung disease or pneumonitis
• Participant has experienced any of the following with prior immunotherapy: any imAE of Grade ≥3, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis of any grade. Non clinically significant laboratory abnormalities are not exclusionary.
• Participant has a known additional malignancy that progressed or required active treatment within the past 2 years. Exceptions include adequately treated superficial skin cancers, superficial bladder cancers, and other in situ cancers.
• Participant 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.
• Participant has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or has known allergies to dostarlimab or its excipients.
• Has received or plans to receive an organ or stem cell transplant that uses donor stem cells (allogeneic stem cell transplant).

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 monotherapy	Biological: Dostarlimab; Dostarlimab will be administered.; Other Names: TSR-042; GSK4057190; JEMPERLI; dostarlimab-gxly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR)	cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 12 months following their post-intervention disease assessment (PIDA)	18 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with discontinuation of study intervention		Up to 24 weeks
Serum concentration of Dostarlimab		Up to 37 weeks
Concentration at the end of infusion (C-EOI) of Dostarlimab		Up to 37 weeks
Trough Concentration (C-trough) of Dostarlimab		Up to 37 weeks
Number of Participants with Anti-Drug Antibodies against Dostarlimab		Up to 37 weeks
Number of Participants with Sustained Complete Clinical Response for 24 Months (cCR24) as assessed by ICR	cCR24 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 24 months following their post-Intervention disease assessment (PIDA)	30 Months
Number of Participants with Sustained Complete Clinical Response for 36 Months (cCR36) as assessed by ICR	cCR36 is achieved when a participant maintains complete clinical response (cCR) as assessed by ICR for 36 months following their post-Intervention disease assessment (PIDA)	42 Months
Number of Participants with Event Free Survival at 3 years (EFS3) as assessed by Investigator	EFS3 is defined as participants who remained alive and free of disease progression precluding surgery, local recurrence, and distant recurrence at 3 years as assessed by Investigator	3 years
Event Free Survival (EFS) as assessed by Investigator	EFS is defined as time from the date of first dose of study intervention to any of the following events: progression of disease that precludes surgery, local recurrence, distant recurrence (all as assessed by the investigator), or death due to any cause	Up to 74 months
Number of Participants with cCR12 as assessed by Investigator	cCR12 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 12 months following their post-intervention disease assessment (PIDA)	18 Months
Number of Participants with cCR24 as assessed by Investigator	cCR24 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 24 months following their post-intervention disease assessment (PIDA)	30 Months
Number of Participants with cCR36 as assessed by Investigator	cCR36 is achieved when a participant maintains complete clinical response (cCR) as assessed by Investigator for 36 months following their post-intervention disease assessment (PIDA)	42 Months
Objective Response Rate (ORR) assessed by ICR	ORR is defined as number of participants achieving a partial response (PR), near complete response (nCR) or complete clinical response (cCR) at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or incomplete clinical response (iCR) (PIDA 2) as assessed by ICR	Up to 33 Weeks
Objective Response Rate (ORR) as assessed by Investigator	ORR by Investigator, defined as achieving a PR, nCR, or cCR at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or iCR	Up to 33 Weeks
Disease-Specific Survival (DSS)	DSS is defined as time from the date of first dose of study intervention to death due to disease	Up to 74 months
Disease-Specific Response at 5 years (DSS5)	DSS5 is defined as the number of participants not dying due to disease under study at 5 years from the first dose of study intervention	Up to 5 years
Overall Survival (OS)	OS is defined as time from first dose of study intervention to death from any cause	Up to 74 months
Overall Survival at 5 years (OS5)	OS is defined as number of participants as being alive at 5 years from first dose of study intervention	Up to 5 years
Organ Preservation Rate	Organ Preservation Rate defined as not undergoing Total Mesorectal Excision (TME), either as primary management or for local recurrence, and who did not have a permanent colostomy created, at any time up to 3 years	3 years
Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Immune mediated Adverse Events (imAEs) based on Severity		Up to 74 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2023
• Primary Completion (Estimated): November 2, 2026
• Study Completion (Estimated): October 11, 2029

Study Registration Dates

• First Submitted: February 2, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 10, 2023

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Neoadjuvant; dMMR; MSI-H; JEMPERLI; dostarlimab-gxly; Stage II/III rectal cancer; GSK4057190
• 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; Antineoplastic Agents; dostarlimab
• Other Study ID Numbers: 219369; 2022-003289-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: GSK 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/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.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 terminated asset(s) 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