COLONYVAQ™, a Quantum-Classical Guided Personalized Neoantigen Vaccine for MSS Stage III Colorectal Cancer

NCT07328087 | Recruiting Early Phase 1 DMC

• 3 other identifiers: BiogeneaTMMyVaccine310210381179COLONYVAQ-CRC P1-Adjuvant-MSS™
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is an early phase I, single-arm, open-label clinical study designed to evaluate the safety, tolerability, and feasibility of COLONYVAQ-CRC, a physics-aware, quantum-classical AI-guided personalized neoantigen peptide vaccine, administered in combination with standard adjuvant oxaliplatin-based chemotherapy (mFOLFOX6 or CAPOX) and nivolumab 3 mg/kg in patients with completely resected stage III microsatellite-stable (MSS) / proficient mismatch repair (pMMR) colorectal cancer. An initial safety cohort of 12 patients will be enrolled and closely monitored for toxicity attributable to the experimental vaccine preparation. If, among these 12 patients, fewer than 3 develop experimental-preparation-related toxicity greater than grade 2 and no patient develops experimental-preparation-related grade 4 toxicity, the study will expand to enroll a total of 50 patients. Primary objectives focus on safety and tolerability of the combination regimen. Secondary and exploratory objectives characterize neoantigen-specific immune responses, ctDNA dynamics, T-cell receptor (TCR) clonotype evolution, tumor immune microenvironment features, and preliminary disease control (disease-free survival and overall survival) to inform subsequent phase II design.

Conditions

Colorectal Cancer Metastatic; Colorectal Cancer Stage III; Colorectal Cancer Stage IV

Keywords

CRC Patient-specific vaccine,; AI-Quantum guided neoantigen selection,; Machine learning-based neoantigen prediction,

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent AEs/SAEs and Immune-Related AEs (CTCAE v5.0) With COLONYVAQ-CRC Plus Chemotherapy and Nivolumab

  Incidence, nature, and severity (CTCAE v5.0 grade) of treatment-emergent adverse events (AEs) and serious adverse events (SAEs), with specific assessment of vaccine-attributable toxicities and immune-related adverse events. A prespecified safety expansion benchmark will be evaluated: among the first 12 patients, \<3 with vaccine-related toxicity \>Grade 2 and no vaccine-related Grade 4 toxicity prior to expansion from 12 to 50 patients.

  From first dose of any study treatment (chemotherapy, vaccine, or nivolumab) through 90 days after the last dose (total observation ~12 months per patient).

Secondary Outcomes (10)

• Feasibility of COLONYVAQ-CRC Vaccine Manufacturing and Delivery

  From enrollment through completion of the prime vaccination phase, typically within the first 8 weeks after the first vaccine dose.

• Proportion of Participants With ≥2-Fold Increase in Neoantigen-Specific T Cells From Baseline

  Baseline (within 28 days before the first vaccine dose), during vaccination at approximately Weeks 4, 12 and 20 after first vaccination, at the end of the vaccination period (around 8 months after first vaccination), and at a 12-month follow-up.

• ctDNA Clearance at End of Adjuvant Chemotherapy

  Postoperative baseline before adjuvant therapy (within 4 weeks prior to the first chemotherapy cycle), during treatment at approximately 3 months and at the end of adjuvant chemotherapy, around 7 months after randomization, and at follow-up at 12 months.

• Preliminary Disease-Free Survival (DFS)

  From the date of first study treatment until first documented recurrence of colorectal cancer or death from any cause, whichever occurs first, with planned descriptive analysis at 36 months after first patient first treatment.

• Preliminary Overall Survival (OS)

  From the date of first study treatment until death from any cause, with follow-up planned up to 60 months after the first patient starts treatment.

Other Outcomes (9)

• T-Cell Receptor (TCR) Clonotype Diversity, Expansion, and Persistence

  Baseline within 28 days prior to first vaccine dose, during vaccination at Weeks 4, 12, and 20 after first vaccination, at the end of the vaccination period approximately at 7 months, and at 12 and 24 months after initiation of adjuvant therapy.

• Correlation of Tumor Immune Features With Vaccine-Induced Systemic Immune Responses

  Baseline resection specimen (pre-treatment) and optional tissue samples at recurrence or predefined timepoints up to 60 months after treatment initiation.

• Clinical Correlation of Genomic and COLONYVAQ Modeling Features With Immune Response Breadth and Clinical Outcomes

  Baseline molecular profiling performed before vaccine manufacture, with clinical and immune outcomes followed up to 60 months after treatment initiation.

Study Arms (1)

Experimental Arm: COLONYVAQ-CRC + Standard Adjuvant Chemotherapy + Nivolumab

EXPERIMENTAL

All enrolled patients receive study treatment after R0 resection of stage III MSS/pMMR colorectal cancer. Standard adjuvant chemotherapy is either mFOLFOX6 or CAPOX, preselected per institutional practice. mFOLFOX6 is given q14d for \~6 months: oxaliplatin 85 mg/m² IV over 2 h, leucovorin 400 mg/m² IV over 2 h, 5-FU 400 mg/m² IV bolus, then 5-FU 2400 mg/m² continuous IV over 46 h. CAPOX is given q21d for \~3-6 months: oxaliplatin 130 mg/m² IV over \~2 h on Day 1 plus capecitabine 1000 mg/m² PO BID on Days 1-14, then 7 days off. COLONYVAQ-CRC is a personalized multi-peptide neoantigen vaccine (≤20 peptides, 8-30 aa, 0.3 mg each), selected by a quantum-classical pipeline, synthesized under GMP, pooled (2-4 pools) and mixed 1:1 with poly I:C (2 mg/mL) to 1 mL for SC injection on a prime-boost schedule (Days 1, 4, 8, 15, 22; Weeks 12, 20). Nivolumab 3 mg/kg IV q2w is given for up to 12 months.

Biological: Experimental: COLONYVAQ-CRC + mFOLFOX6 or CAPOX + Nivolumab

Interventions

Experimental: COLONYVAQ-CRC + mFOLFOX6 or CAPOX + Nivolumab BIOLOGICAL

Intervention Type: Biological Intervention Name: COLONYVAQ-CRC (Personalized Neoantigen Peptide Vaccine) Description: COLONYVAQ-CRC is a personalized multi-peptide neoantigen vaccine composed of up to 20 patient-specific synthetic peptides (8-30 amino acids; 0.3 mg per peptide per dose). Neoantigens are selected from tumor/normal whole-exome and tumor RNA sequencing using the COLONYVAQ quantum-classical pipeline (including HLA typing, quantum-geometric similarity, thermodynamic docking, and calibrated immunogenicity scoring). Peptides passing all physics-immunology gates are synthesized under GMP, grouped into 2-4 pools (≤5 peptides/pool in 500 µL), and mixed 1:1 with Montamide (2 mg/mL) to a final volume of 1 mL for subcutaneous injection into lymph node-rich regions (e.g., bilateral axillae/groins). Vaccination follows a prime-boost schedule (e.g., Days 1, 4, 8, 15, 22; booster doses around Weeks 12 and 20), coordinated with chemotherapy.

Experimental Arm: COLONYVAQ-CRC + Standard Adjuvant Chemotherapy + Nivolumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \*\*Diagnosis / Histology\*\*
• Histologically confirmed adenocarcinoma of the colon or rectum.
• Pathology report available for central or sponsor review (if requested), including:
• Primary tumor site (colon vs rectum)
• Grade of differentiation
• Resection margins
• \*\*Stage and Surgical Status\*\*
• Pathologic stage III disease (any T, N1-2, M0) per AJCC 8th edition.
• R0 resection of the primary tumor documented by operative and pathology reports (no macroscopic or microscopic residual tumor at margins).
• No evidence of distant metastatic disease (M1) on staging imaging (CT chest/abdomen/pelvis ± MRI/PET per institutional standard) within a protocol-defined window (e.g., ≤8 weeks prior to enrollment).
• Enrollment and treatment initiation planned within a protocol-defined timeframe after surgery (e.g., 4-12 weeks post-resection), allowing appropriate recovery.
• \*\*Molecular Subtype (MSS/pMMR)\*\*
• Tumor confirmed MSS or pMMR by local testing using one or more of the following:
• IHC for MLH1, MSH2, MSH6, and PMS2
• PCR-based MSI panel

You may not qualify if:

• \*\*Residual or Metastatic Disease at Baseline\*\*
• R2 resection or indeterminate margins not clearly R0.
• Radiologic or histologic evidence of distant metastases (M1) at baseline staging (e.g., liver, lung, peritoneum).
• Gross residual disease at the primary site.
• \*\*Mismatch Repair-Deficient / MSI-High / POLE-Ultramutated Disease\*\*
• Known dMMR/MSI-H CRC or POLE ultramutated tumors for which checkpoint inhibition is standard/preferred.
• \*\*Prior Anticancer Therapy (Beyond Allowed Neoadjuvant)\*\*
• Prior systemic therapy for metastatic CRC.
• Neoadjuvant chemotherapy/chemoradiotherapy that:
• Was not completed within protocol-defined windows, \*\*or\*\*
• Led to unresolved Grade ≥2 non-hematologic toxicity (excluding alopecia or clinically insignificant neuropathy, per protocol)
• Prior tumor vaccine targeting TAAs or neoantigens (peptide, DC, viral, RNA, or DNA).
• Prior immune checkpoint inhibitor therapy (anti-PD-1, anti-PD-L1, anti-CTLA-4).
• \*\*Active or Uncontrolled Infections\*\*
• Systemic infection requiring IV or oral antimicrobials that would interfere with study treatment per investigator judgment.

Sponsors & Collaborators

• Biogenea Pharmaceuticals Ltd.: lead
• Interbalkan Medical Center, Thessaloniki, Greece: collaborator

Study Sites (1)

Biogenea Pharmaeuticals Ltd

Thessaloniki, 54627, Greece

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ioannis Grigoriadis, Pharmacist PharmD

  Biogenea Pharmaceuticals Ltd.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ioannis Grigoriadis, PharmacistPharmD

CONTACT

+306936592686; BIOGENEADRUG@GMAIL.COM

Christos Emmanouelides, MD, PhD, Medical Oncologist,

CONTACT

+306972221474; cemmanou@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Twelve patients will enroll in the initial safety cohort. If, among these 12 patients, fewer than 3 experience toxicity greater than grade II (grade III or IV) attributed to the experimental vaccine preparation and no patient experiences experimental-preparation-related grade IV toxicity, the study will expand to enroll a total of 50 patients. If these criteria are not met, the protocol and dose/schedule may be revised and further enrollment paused or modified. Estimated Enrollment: 12 patients in the initial safety phase; up to 50 patients in total upon expansion.

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: January 8, 2026
• Study Start: February 2, 2026
• Primary Completion (Estimated): December 2, 2030
• Study Completion (Estimated): December 2, 2031
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)