Oncolytic Virotherapy to Enhance PReoperative IMmunotherapy Efficacy in Patients With Proficient Mismatch Repair (pMMR) Rectal Cancer

NCT07687875 | Recruiting Phase 1 DMC

• 2 other identifiers: P2025-190922025-524375-23-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I clinical trial that will investigate the safety and tolerability of combining the modified vaccinia virus BT-001 with systemic pembrolizumab in patients with localised pMMR rectal cancer

Conditions

Rectal Cancer Patients

Keywords

Rectal Cancer; Immunotherapy; Oncolytic Virotherapy; Proficient mismatch repair

Outcome Measures

Primary Outcomes (3)

• Overall incidence of adverse events (AEs)

  Evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Within 30 days of the end of the study treatment

• Overall incidence of serious adverse events (SAEs)

  Evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Within 30 days of the end of the study treatment

• Overall incidence of dose limiting toxicities (DLTs)

  Incidence of dose-limiting toxicities

  Within 30 days of the end of the study treatment

Secondary Outcomes (5)

• Clinical efficacy of BT-001 when delivered by endoscopic/transrectal ultrasound guided intra-tumoural injection in combination with a single systemic dose of pembrolizumab in patients with primary, localised, rectal cancer with proficient mismatch repair

  Within 6 weeks of the start of the study treatment

• Effects of the study treatment on long-term oncological outcomes

  Up to 5 years after the end of the study treatment

• Determine the effects of the study treatment on patient's quality of life

  Up to 5 years after the end of the study treatment

• Determine the effects of the study treatment on patient's quality of life

  Up to 5 years after the end of the study treatment

• Determine the effects of the study treatment on patient's quality of life

  Up to 5 years after the end of the study treatment

Study Arms (1)

Treatment with BT-001 and pembrolizumab

EXPERIMENTAL

Two doses of BT-001 delivered by intra-tumoural injection followed by one systemic dose of pembrolizumab

Drug: BT-001 followed by Pembrolizumab (PD-1 Blocking Antibody)

Interventions

BT-001 followed by Pembrolizumab (PD-1 Blocking Antibody) DRUG

Two doses of BT-001 delivered by intra-tumoural injection followed by one systemic dose of pembrolizumab

Treatment with BT-001 and pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis of primary, localised rectal adenocarcinoma (cT2N0M0 to cT3bN2M0, TNM classification version 8
• Diagnosis of Proficient Mismatch Repair (pMMR) rectal adenocarcinoma (using biopsy from the initial diagnostic endoscopy)
• Suitable for potentially curative surgical resection
• No contraindications for treatment with pembrolizumab
• Not requiring neoadjuvant therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Have baseline laboratory results as follows:
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
• Platelets ≥ 100 ×109/L (without platelet transfusion)
• Haemoglobin ≥ 6.2 mmol/L or 10.0 g/dL (with or without red blood cell (RBC) transfusion)
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
• Bilirubin \< 1.5 × ULN (or \< 2.5 x ULN in patients with Gilbert's syndrome)
• ALT, AST and alkaline phosphatase \< 3 × ULN
• Provide written informed consent in accordance with all applicable regulations and follow the study procedures. Subjects must be capable of understanding the investigational nature, potential risks, and benefits of the study.

You may not qualify if:

• Have impending bowel obstruction or other indications for acute surgical intervention
• Have had concurrent immunotherapy in the 3 months before the start of the study therapy.
• Have acute or chronic hepatitis B or hepatitis C infection
• Evidence of immunosuppression for any reason:
• Known HIV disease
• Chronic oral or systemic steroid medication use at a dose of \> 10 mg/day of prednisolone or equivalent
• Other signs or symptoms of clinical immune system suppression
• Have an autoimmune disorder (except thyroiditis with replacement therapy and type I diabetes mellitus)
• Have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Ongoing antiviral therapy active on vaccinia virus, e.g., ribavirin, cidofovir, interferon/ pegylated interferon
• History of severe exfoliative skin conditions (e.g., eczema or atopic dermatitis) requiring systemic therapy for more than 4 weeks within 2 years prior to BT-001 initiation
• Live virus vaccination within 28 days of BT-001 administration
• A history of hypersensitivity to egg or to any excipient of BT-001
• Pregnant or breast-feeding female. Confirmation that women of childbearing potential are not pregnant with a negative serum β-human chorionic gonadotrophin (β-hCG) pregnancy test results must be obtained within 7 days prior to the 1st administration of BT-001
• Fertile males and females who are unwilling to employ highly effective means of contraception during study treatment and for 4 months after the last dose of study treatment

Sponsors & Collaborators

• Henry Smith: lead
• Transgene: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Copenhagen University Hospital - Bispebjerg and Frederiksberg

Copenhagen, Captial Region, 2400, Denmark

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Henry G Smith, PhD

CONTACT

+4521701936; henry.george.smith@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 20, 2026
• First Posted: July 7, 2026
• Study Start: June 17, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2033
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in relevant independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Locations

DK (1)