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

A Phase I Study of the Safety and Efficacy of a Modified Vaccinia Virus (BT-001) Delivered by Endoscopic Intra-tumoural Injection Followed by Systemic Antiprogammed Death-1 (Anti-PD-1) Antibodies in Patients With Localised Rectal Cancer With Proficient Mismatch Repair (pMMR)

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

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer Patients
• Intervention / Treatment: Drug: BT-001 followed by Pembrolizumab (PD-1 Blocking Antibody)

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Henry G Smith, PhD; Phone Number: +4521701936; Email: henry.george.smith@regionh.dk

Study Locations

• Denmark
  • Captial Region
    • Copenhagen, Captial Region, Denmark, 2400
      • Recruiting
      • Copenhagen University Hospital - Bispebjerg and Frederiksberg
      • Contact: Henry G Smith, PhD; Phone Number: +4521701936; Email: henry.george.smith@regionh.dk
      • Contact: Mette B Barrit; Phone Number: +4538635602; Email: mette.brogaard.barrit@regionh.dk
      • Principal Investigator: Henry G Smith, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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
• Aged > 18 years at the time of inclusion
• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Treatment with BT-001 and pembrolizumab; 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); Two doses of BT-001 delivered by intra-tumoural injection followed by one systemic dose of pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Defined as the proportion of patients achieving a complete or major pathological response.	Within 6 weeks of the start of the study treatment
Effects of the study treatment on long-term oncological outcomes	Percentage of patients developing local recurrence and/or distant metastases at 1-, 3- and 5-years' follow-up	Up to 5 years after the end of the study treatment
Determine the effects of the study treatment on patient's quality of life	Assessed using the EORTC QLQ CR29 questionnaire at baseline, 1 month after surgery, and 1-, 3- and 5-years' follow-up	Up to 5 years after the end of the study treatment
Determine the effects of the study treatment on patient's quality of life	Assessed using the EQ 5D questionnaire at baseline, 1 month after surgery, and 1-, 3- and 5-years' follow-up	Up to 5 years after the end of the study treatment
Determine the effects of the study treatment on patient's quality of life	Assessed using the LARS questionnaire at baseline, 1 month after surgery, and 1-, 3- and 5-years' follow-up	Up to 5 years after the end of the study treatment

Collaborators and Investigators

• Sponsor: Henry Smith
• Collaborators: Rigshospitalet, Denmark; Transgene

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: June 20, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Rectal Cancer; Oncolytic Virotherapy; Proficient mismatch repair
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: P2025-19092; 2025-524375-23-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie the results of this study may be shared after de-identification. 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).
• IPD Sharing 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.
• IPD Sharing 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).

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