AZUR-2: Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05855200

Collaborator

(none)

711

Enrollment

Arms

90.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the efficacy of perioperative dostarlimab compared with standard of care (SOC) in participants with untreated T4N0 or Stage III (resectable), defective mismatch repair/ microsatellite instability high (dMMR/MSI-H) colon cancer.

Condition or Disease	Intervention/Treatment	Phase
Colonic Neoplasms	Biological: Dostarlimab Drug: CAPEOX Drug: FOLFOX	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

711 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

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Primary Purpose:

Treatment

Official Title:

A Phase 3, Open-Label, Randomized Study of Perioperative Dostarlimab Monotherapy Versus Standard of Care in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer

Anticipated Study Start Date :

Jun 23, 2023

Anticipated Primary Completion Date :

Dec 15, 2028

Anticipated Study Completion Date :

Dec 25, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dostarlimab Participants will receive Dostarlimab pre and post surgery	Biological: Dostarlimab Dostarlimab will be administered.
Active Comparator: Standard of Care (SOC) Participants will receive SOC (FOLFOX/CAPEOX) or undergo expectant observation post surgery.	Drug: CAPEOX CAPEOX will be administered. Drug: FOLFOX FOLFOX will be administered.

Arm

Intervention/Treatment

Experimental: Dostarlimab

Participants will receive Dostarlimab pre and post surgery

Biological: Dostarlimab

Dostarlimab will be administered.

Active Comparator: Standard of Care (SOC)

Participants will receive SOC (FOLFOX/CAPEOX) or undergo expectant observation post surgery.

Drug: CAPEOX

CAPEOX will be administered.

Drug: FOLFOX

FOLFOX will be administered.

Outcome Measures

Primary Outcome Measures

Event-free Survival (EFS) Assessed by Blinded Independent Central Review (BICR) [Up to approximately 5 years]
EFS is defined as the time from randomization to either disease recurrence or death due to any cause or treatment related toxicity that results in the participant not being suitable for surgery

Secondary Outcome Measures

Number of Participants with Pathological Response [Up to approximately 5 years]
Pathological response will be categorized as a complete pathologic response, major pathologic response, partial pathologic response, or negligible pathologic response.
Overall Survival (OS) [Up to approximately 5 years]
OS is defined as time from randomization to death from any cause
Event-free Survival (EFS) assessed by local assessment [Up to approximately 5 years]
EFS is defined as the time from randomization to either disease recurrence or death due to any cause or treatment related toxicity that results in the participant not being suitable for surgery
Number of Participants with treatment emergent adverse events (AEs), serious adverse events (SAEs), Immune-related Adverse Event (irAEs), AEs leading to death and AEs leading to discontinuation of study treatment [Up to approximately 5 years]
Number of Participants with AEs and SAEs by Severity [Up to approximately 5 years]
Serum Concentration of Dostarlimab [Predose and End of Infusion (EoI) of Cycle 1 and EoI of Cycle 2 to Cycle 10 (each cycle is of 21 days)]
Serum Concentration of Dostarlimab at End of Infusion (C-EoI) [End of Infusion (EoI) of Cycle 1 to Cycle 10 (each cycle is of 21 days)]
Serum Predose trough concentration (Ctrough) of Dostarlimab [Predose of Cycle 1 to Cycle 10 (each cycle is of 21 days)]
Number of Participants with Anti-Drug Antibodies against Dostarlimab [Up to approximately 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Has untreated pathologically confirmed colon adenocarcinoma
Has resectable colon adenocarcinoma defined as clinically T4N0 or Stage III
Has radiologically evaluable disease
Has a tumor demonstrating the presence of either dMMR status or MSI-H

Exclusion Criteria:

Has distant metastatic disease.
Has received prior medical therapy (chemotherapy, immunotherapy, biologic, or targeted therapy), radiation therapy or surgery for management of colon cancer
Has a tumor that, in the investigator's judgment is causing symptomatic bowel obstruction or otherwise requires urgent/emergent surgery
Has undergone any major surgical procedure, open biopsy, or experienced significant traumatic injury within 28 days prior to enrollment
Has any history of interstitial lung disease or pneumonitis
Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice
Has a history of allogenic stem cell transplantation or organ transplantation
Is receiving any other anticancer or experimental therapy. No other experimental therapies (including but not limited to chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, or other experimental drugs) of any kind are permitted while the participant is receiving study intervention
Is pregnant, breastfeeding, or expecting to conceive children within the projected duration of the study
Has a history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or known allergies to dostarlimab, or its excipients, or any components of FOLFOX or CAPEOX