Single Arm Study of Neoadjuvant Dostarlimab in Stage II and III Deficient Mismatch Repair Colon Cancers

NCT05239546 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202105539
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II, single arm study looking at the rate of major clinical response and non-operative management in Stage II and III colon cancer after 18 weeks (up to 6 cycles) of neoadjuvant dostarlimab.

Conditions

Colon Cancer; dMMR Colorectal Cancer

Keywords

Colon cancer; dMMR; Deficient mismatch repair colon cancer; MSI-High; MSI-H; Non-operative management; No surgery

Outcome Measures

Primary Outcomes (1)

• Major Clinical Response (MCR) Rate

  MCR rate is defined as the proportion of patients meeting the following criteria at 18 weeks: 1) ctDNA is stable or declining, 2) a clinically asymptomatic primary tumor, and 3) no metastatic disease.

  From Dostarlimab initiation to 18 weeks.

Secondary Outcomes (3)

• Metastasis-Free Survival (MFS) Prior to Surgery

  From Dostarlimab initiation until surgery or Dostarlimab completion, up to 2 years.

• Progression-Free Survival (PFS)

  From treatment Dostarlimab until study completion, up to 5 years.

• Overall Response Rate (ORR)

  From Dostarlimab initiation until surgery or Dostarlimab completion, up to 2 years.

Study Arms (1)

Neoadjuvant Dostarlimab

EXPERIMENTAL

Participants will receive Dostarlimab 500 mg IV every 3 weeks for 6 cycles followed by 1000 mg every 6 weeks for 8 cycles until 1.5 years

Drug: Dostarlimab

Interventions

Dostarlimab DRUG

Participants will receive Dostarlimab 500 mg IV every 3 weeks for 6 cycles followed by 1000 mg every 6 weeks for 8 cycles until 1.5 years

Also known as: TSR-042

Neoadjuvant Dostarlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of understanding and complying with the protocol requirements and have signed the informed consent document. Patients with mild cognitive impairment may be considered for enrollment in the study if their legally authorized representative provides written informed consent for the patient.
• years or older in age
• Biopsy proven dMMR (by IHC), Stage II or III colon cancer per CT imaging correlation with AJCC 8th edition, 2017, amendable to en block surgical resection as determined by colorectal surgeon.
• Biopsy specimen for diagnosis of dMMR Colon cancer should have enough tissue for minimum 4 and max 6 adjacent unstained FFPE slides (4µm each) as determined by Protocol Pathologist Dr. Anthony Snow for CD3+ and CD8+ analysis. If there is not enough tissue present in original sample, a repeat colonoscopy and biopsy may be performed; otherwise patient is not eligible.

You may not qualify if:

• ECOG performance status less than or equal to 1
• Absence of metastatic disease on CT CAP with Contrast within 28 days from treatment start
• Absolute neutrophil count greater than or equal to 1,500/µL
• Platelets greater than or equal to 100,000/µL
• Hemoglobin greater than or equal to 9 g/dL
• Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 60mL/min using the Cockcroft-Gault equation
• Total bilirubin less than or equal to 1.5 x ULN (less than or equal to 2.0 in patients with known Gilberts syndrome) OR direct bilirubin less than or equal to 1 x ULN
• Aspartate aminotransferase and alanine aminotransferase less than or equal to 3.0 x ULN
• International normalized ratio (INR) or prothrombin time (PT) less than or equal to 1.5× ULN unless patient is receiving anticoagulant therapy if PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) less than or equal to 1.5× ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants
• Participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to taking study treatment and agree to use an adequate method of contraception from screening through 180 days after the last dose of study treatment. 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.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner starting with first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
• Synchronous primary tumor (i.e. more than 1)
• Obstruction or perforation requiring diverting ostomy or immediate resection, or bright red blood per rectum requiring urgent blood transfusion, from their primary tumor.
• Clinical T4b tumors
• Known hypersensitivity to dostarlimab components or excipients.

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Saima M Sharif, MD, MS

  University of Iowa Holden Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Saima Sharif, MD, MS

CONTACT

319-356-1616; saima-sharif@uiowa.edu

Alisha Demsky

CONTACT

319-384-5461; alisha-demsky@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: February 15, 2022
• Study Start: March 24, 2023
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)