Phase II Study of Neoadjuvant Dostarlimab in Patients With Untreated T3-4N0-2 or Stage III pMMR/MSS Resectable Colon Cancer (Superhero)

Early Phase II Exploratory, Open-Label, Non-Randomized Study of Neoadjuvant Dostarlimab Monotherapy in Participants With Untreated T3-4N0-2 or Stage III pMMR/MSS Resectable Colon Cancer

Dostarlimab belongs to a class of drugs called PD-1 inhibitors that use your own immune system to treat cancer (immunotherapy). It is designed to stop cancer from growing by helping your immune system recognize and fight the cancer. This investigational medicinal product (IMP) has been approved by the Belgian authorities, but not for the treatment of colon cancer.

It is known that a small number of patients with pMMR/MSS colon cancer may have significant response to medication of this type (immunotherapy) depending on each person's biology.

Trial intervention for all patients will be neo-adjuvant dostarlimab 500 mg IV, given alone by intravenous infusion. Two administrations of dostarlimab are foreseen, at three weeks interval, before surgery for your colon cancer. It has not yet been proven that this treatment can cure, improve or stabilise your disease or condition.

The study aims to investigate specific molecular changes in tumour and blood after dostarlimab monotherapy administered and before surgery which could be associated with improved response to conventional treatment in some patients. If you decide to participate, as the duration of treatment with dostarlimab is 6 weeks, surgery may be slightly delayed compared to patients that are not treated with dostarlimab and go directly for surgery. It remains uncertain if this is beneficial in your personal situation but some patients might experience significant response. The risks have been carefully assessed and the potential benefits for some patients are considered important and justify undertaking the treatment.

Subsequent therapy after surgery remains at the discretion of the treating physician.

The duration of a patient on trial will last up to 4 months from the first dose of dostarlimab and afterwards 2 years of follow up is applicable.

Study Overview

• Status: Recruiting
• Conditions: Colon Cancer Stage III
• Intervention / Treatment: Drug: Dostarlimab

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sabine Tejpar, MD; Phone Number: +32 16 34 42 25; Email: sabine.tejpar@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZLeuven
    • Contact: Sabine Tejpar, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• at least 18 years of age and capable of giving informed consent
• primary adenocarcinoma colon cancer than can be removed surgically, staged cT3-4, cN0-2, cM0 or stage III
• tumour expresses an MMR proficient/microsatellite stable called MSS
• tissue samples from tumour and colon mucosa available for molecular analyses
• capable of receiving immunotherapy
• adequate general health status and organ function (blood tests)

Exclusion Criteria:

• no prior cancer treatment
• not pregnant and using effective contraception if applicable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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; Dostarlimab should be administered by intravenous infusion using an intravenous infusion pump over 30 minutes at a dose of 500 mg once every 3 weeks (Q3W), for 2 cycles (6 weeks in total).

Drug: Dostarlimab; Dostarlimab [Jemperli GlaxoSmithKline (GSK)] is a humanized IgG4 monoclonal antibody that binds with high affinity and specificity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. Dostarlimab is in clinical development for the treatment of subjects with solid tumors, including those with recurrent/advanced dMMR/MSI-H solid tumors who have progressed on standard of care chemotherapy, as monotherapy or in combination with other agents.; Other Names: Jemperli

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multi-omic exploration	Data generation through multi-omic exploration of blood and tissue derived products (see Sampling and Lab manual). Correlation of molecular-biological features identified with pathological response. The presence or absence of specific molecular characteristics in blood and tissue will be correlated in each patient with the degree of tumour response to therapy evaluated by a pathologist.	From enrollment to the last FU visit of the patient for blood (2 years). From baseline to surgery for tissue (12-15 weeks). Data will be reported at the final study report (max 3 years from study start).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety analysis	Safety analysis. Frequency and severity of treatment emergent AEs, SAEs, irAEs. AEs leading to death, discontinuation of trial intervention or resulting in the participant not being suitable for surgery.	Continuous
Pathological response	Proportion of participants with pathological response, determined by local assessment.	Pathological tumor staging and response assessment is at surgery
Survival	Survival time defined from Superhero ICF signature to death from any cause. Proportion of survivors at 2 years. Event free survival time (EFS) defined from Superhero ICF signature to recurrence evaluated by local assessment or death.	From enrollment till last FU visit of patient (2 years). Data will be reported at the final study report (max 3 years from study start).

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Sabine Tejpar, MD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): February 17, 2025

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Resectable; Neoadjuvant; Colon Cancer; pMMR/MSS
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Colonic Neoplasms; Antineoplastic Agents; dostarlimab
• Other Study ID Numbers: S68882; 2024-512499-36-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No