A Phase I Trial of IMA970A Plus Montanide in Combination With Durvalumab (Anti-PD-L1)

NCT06218511 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: HEPAVAC 20146/22
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is designed as a single-arm, open-label, phase I study investigating an off-the-shelf, multi-peptide-base HCC vaccine plus Montanide, combined with Durvalumab in patients with very early, early and intermediate stage of HCC. The investigational agents will be applied without concomitant anti-tumour therapy with the intention to reduce risk of recurrence/progression in patients who have received all indicated standard treatments.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Safety assessments will consist of continuous monitoring and reporting of adverse events (AEs) including serious adverse events (SAEs), regular monitoring of vital signs, ECOG performance status and regular conduct of physical examinations and laboratory assessments (haematology, clinical \[bio\]chemistry including C reactive protein (CRP) and glomerular filtration rate (GFR), coagulation test, assessment of viral infection, thyroid function test (TFT), urinalysis), electrocardiogram (ECG) and pregnancy tests (if applicable). Possible cross-reactivity with live attenuated vaccination or flu vaccine will be assessed.

  55 months (approximately 4.5 years)

Secondary Outcomes (5)

• Additional immunological parameters in blood (e.g. regulatory T-cells, myeloid derived suppressor cells)

  55 months (approximately 4.5 years)

• Infiltrating T-lymphocytes, immune cells and potential other (bio)markers in tumour tissue (depending on availability of tissue)

  55 months (approximately 4.5 years)

• DFS

  55 months (approximately 4.5 years)

• PFS

  55 months (approximately 4.5 years)

• OS

  Patients will be followed for overall survival every 2 months for up to 2 years after having completed the interventional part of the study at EOS.

Other Outcomes (5)

• Immunogenicity

  55 months (approximately 4.5 years)

• Additional immunological parameters

  55 months (approximately 4.5 years)

• Infiltrating T-lymphocytes in tissue

  55 months (approximately 4.5 years)

Study Arms (1)

Single arm

EXPERIMENTAL

single-arm open-label

Biological: Peptide-based hepatocellular carcinoma vaccine IMA970A; Combination Product: Durvalumab; Other: Montanide (Adjuvant)

Interventions

Peptide-based hepatocellular carcinoma vaccine IMA970A BIOLOGICAL

IMA970A is a lyophilized multi-peptide vaccine consisting of 17 individual peptides (active pharmaceutical ingredients) and 2 excipients (Poloxamer 338 and Mannitol). All peptides have been chemically manufactured by well established solid phase peptide synthesis procedures. All peptides are composed of linear, unmodified L- amino acid chains with chain length in the range of 9 to 21 amino acids.

Single arm

Durvalumab COMBINATION_PRODUCT

anti-PD-L1

Single arm

Montanide (Adjuvant) OTHER

Montanide ISA™ 51 is a water-in-oil (W/O) emulsion composed of a mineral oil and a surfactant from the mannide monooleate family with immune stimulatory effect .

Single arm

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years at time of study entry.
• HLA type: HLA-A\*02 and/or HLA-A\*24 positive.
• Very early, early and intermediate stage (Barcelona Clinic Liver Cancer (BCLC) stage 0, A, B disease) hepatocellular carcinoma (HCC) diagnosed by biopsy or resected tissue (patho-histological diagnosis) or imaging findings (non-invasive criteria) following any standard treatment (e.g. hepatic resection, Radiofrequency Ablation / Percutaneous Ethanol injection (RFA/PEI), Transarterial chemoembolization (TACE) and SIRT) and without any evidence of active disease that warrant further treatment.
• Minimum life expectancy of 1 year.
• Patho-histological diagnosis of HCC based on biopsy is required for all nodules occurring in non-cirrhotic livers, and for those cases with inconclusive or atypical imaging appearance in cirrhotic livers.
• Non-invasive criteria can only be applied to cirrhotic patients and need to be based on imaging techniques obtained by 4-phase multidetector CT scan or dynamic contrast enhanced MRI and on the identification of the typical hallmark of HCC (hypervascular in the arterial phase with washout in the portal venous or delayed phase). One imaging technique is sufficient for nodules beyond 1 cm (\> 1 cm) in diameter.
• Patients for whom no standard anti-tumour therapy is indicated for the next 3 months thereafter any standard anti-tumour therapies applied for the treatment of BCLC stage 0, A and B HCC (e.g. RFA/PEI, TACE, and SIRT) are allowed to be applied in combination with the study treatment. Patients for whom treatment for advanced disease (e.g.
• sorafenib) is indicated will be withdrawn from study treatment.

You may not qualify if:

• Child-Pugh A5-6 and B7 disease or no liver function impairment.
• Body weight \>30 kg.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.0 × 109 /L
• Platelet count ≥75 × 109
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤5 x institutional upper limit of normal
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min)
• = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min)
• = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

Luigi Buonaguro

Naples, Napoli, 80131, Italy

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab; Monatide (IMS 3015); Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Paolo Antonio Ascierto

  IRCCS I.N.T. "G. Pascale"

  PRINCIPAL INVESTIGATOR

• Francesco Izzo

  IRCCS I.N.T. "G. Pascale"

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Open-label

Study Record Dates

• First Submitted: October 30, 2023
• First Posted: January 23, 2024
• Study Start: November 22, 2022
• Primary Completion: August 28, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 22, 2025

Record last verified: 2025-07

Locations

IT (1)