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NCT Number: NCT05723562

A Study of Dostarlimab in Untreated 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Neoplasms, Rectal Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Rectal Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site, Ottawa, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Dostarlimab

Biological

Dostarlimab will be administered.

Other names: JEMPERLI, dostarlimab-gxly, TSR-042, GSK4057190

Primary outcomes

  1. Number of Participants with Sustained Complete Clinical Response for 12 Months (cCR12) as assessed by Independent Central Review (ICR)

    Time frame: 18 Months

    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)

Secondary outcomes

  1. Number of Participants with Sustained Complete Clinical Response for 24 Months (cCR24) as assessed by ICR

    Time frame: 30 Months

    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)

  2. Number of Participants with Sustained Complete Clinical Response for 36 Months (cCR36) as assessed by ICR

    Time frame: 42 Months

    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)

  3. Number of Participants with Event Free Survival at 3 years (EFS3) as assessed by Investigator

    Time frame: 3 years

    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

  4. Event Free Survival (EFS) as assessed by Investigator

    Time frame: Up to 74 months

    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

  5. Number of Participants with cCR12 as assessed by Investigator

    Time frame: 18 Months

    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)

  6. Number of Participants with cCR24 as assessed by Investigator

    Time frame: 30 Months

    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)

  7. Number of Participants with cCR36 as assessed by Investigator

    Time frame: 42 Months

    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)

  8. Objective Response Rate (ORR) assessed by ICR

    Time frame: Up to 33 Weeks

    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

  9. Objective Response Rate (ORR) as assessed by Investigator

    Time frame: Up to 33 Weeks

    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

  10. Organ Preservation Rate

    Time frame: 3 years

    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

  11. Disease-Specific Survival (DSS)

    Time frame: Up to 74 months

    DSS is defined as time from the date of first dose of study intervention to death due to disease

  12. Disease-Specific Response at 5 years (DSS5)

    Time frame: Up to 5 years

    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

  13. Overall Survival (OS)

    Time frame: Up to 74 months

    OS is defined as time from first dose of study intervention to death from any cause

  14. Overall Survival at 5 years (OS5)

    Time frame: Up to 5 years

    OS is defined as number of participants as being alive at 5 years from first dose of study intervention

  15. Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), Immune mediated Adverse Events (imAEs) based on Severity

    Time frame: Up to 74 months

  16. Number of Participants with discontinuation of study intervention

    Time frame: Up to 24 weeks

  17. Serum concentration of Dostarlimab

    Time frame: Up to 37 weeks

  18. Concentration at the end of infusion (C-EOI) of Dostarlimab

    Time frame: Up to 37 weeks

  19. Trough Concentration (C-trough) of Dostarlimab

    Time frame: Up to 37 weeks

  20. Number of Participants with Anti-Drug Antibodies against Dostarlimab

    Time frame: Up to 37 weeks

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

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

Acronym: AZUR-1

Important dates

Study start
2023
Primary completion
2026
Study completion
2029
First posted
Feb 10, 2023
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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