IMA970A Plus CV8102 in Very Early, Early and Intermediate Stage Hepatocellular Carcinoma Patients

NCT03203005 | Completed Phase 1 DMC

• 1 other identifier: HepaVac-101
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 6

Brief Summary

This study is being carried out in order to evaluate a new cancer vaccine called IMA970A combined with CV8102, a new adjuvant for the treatment of liver cancer (hepatocellular carcinoma). It will be investigated whether IMA970A and CV8102 is safe and can trigger an immune response against the tumor, which may prevent the tumor (cancer) from recurring or spreading or may even lead to tumor shrinkage following the standard treatments the patients have previously received.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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 (hematology, 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). Additionally, an Independent Data Safety Monitoring Board (DSMB) will be implemented to evaluate safety data independently and at defined intervals.

  Through study completion, up to two years

• Immunogenicity (T-cell response in peripheral blood)

  The assessment of immunogenicity will be performed for all patients using standardized immunomonitoring assays. Peripheral blood mononuclear cells (PBMCs) of patients will be analyzed for the occurrence of T-cell responses to peptides contained in IMA970A vaccine before application of standard therapy, such as before and after vaccination. The induction of immune responses by IMA970A vaccine will be subsequently analyzed.

  Up to two years

Secondary Outcomes (5)

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

  Up to two years

• Infiltrating T-lymphocytes, immune cells and potential other (bio)markers in tumor tissue

  Up to two years

• Assessment of the potential impact of the standard therapy on the natural imune response to peptides contained in IMA970A

  Up to two years

• Time to progression (TTP)

  Up to two years

• Overall survival (OS)

  Patients will be followed for overall survival every 2 months for up to 3 years, after having completed the interventional part of the study at EOV/Visit 10.

Study Arms (1)

IMA970A plus CV8102 and Cyclophosphamide

EXPERIMENTAL

Investigational treatment with IMA970A, CV8102, Cyclophosphamide

Drug: IMA970A plus CV8102 and Cyclophosphamide

Interventions

IMA970A plus CV8102 and Cyclophosphamide DRUG

Study treatment starts with a single intravenous infusion of 300mg/m2 Cyclophosphamide. Three days later patients start vaccination therapy with IMA970A plus CV8102 Each vaccination consists of a dose of 6.80 milligrams (mg) IMA970A (containing approx. 400 micrograms \[µg\] of each individual peptide) followed by a dose of 50 µg CV8102. First IMA970A is injected intradermally (i.d.) and about 10 minutes later CV8102 is injected i.d. at the same vaccination site in close proximity. Patients will receive 4 vaccinations at weekly intervals followed by 5 vaccinations at 3-weekly intervals for a total duration of about 4.5 months.

Also known as: Cyclophosphamide Injection 1 g

IMA970A plus CV8102 and Cyclophosphamide

Eligibility Criteria

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

You may qualify if:

• Aged at least 18 years
• HLA type: HLA-A\*02 and/or HLA-A\*24 positive (Screening 1)
• 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 (pathohistological 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
• Pathohistological 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 multi-detector 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-tumor therapy is indicated for the next 3 months (until after visit 7); thereafter any standard anti-tumor 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0
• Child-Pugh A5-6 and B7 disease or no liver function impairment
• Able to understand the nature of the study and give written informed consent
• Willingness and ability to comply with the study protocol for the duration of the study
• Female patients who are post-menopausal (no menstrual period for a minimum of 1 year without any alternative medical cause), or surgically sterile (bilateral salpingectomy, bilateral oophorectomy, or hysterectomy) or practice a highly effective method of birth control from signing of IC 2 by the patient to visit 10/EoV or last study visit
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation applied intravaginal or transdermal for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before first study drug application
• Progestogen-only hormonal contraception associated with inhibition of ovulation applied via injection or implant for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before first study drug application
• Total abstinence from sexual intercourse is acceptable, if it was established prior to the trial and if this is the preferred and usual lifestyle of the patient.
• Intrauterine device (IUD) and intrauterine hormone-releasing system (IUS).

You may not qualify if:

• Any prior systemic anti-tumor treatment (including drug or treatment regimen, approved or experimental) within 2 weeks before CY application
• Concurrent participation in a clinical trial
• Liver transplanted patients; patients who are on the liver transplantation waiting list are allowed to be enrolled
• History of other malignancies within the last 3 years except for adequately treated except cervical carcinoma in situ, basal cell carcinoma and superficial bladder tumors \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to signing of IC 2 by the patient
• Patients with a history or evidence of systemic autoimmune disease, e.g. rheumatoid arthritis, multiple sclerosis, systemic lupus erythematodes (SLE), scleroderma, Sjögren's syndrome, Wegener's granulomatosis, Guillain-Barre syndrome
• Need for concomitant treatment with immunosuppressive drugs or other immune-modifying drugs. The use of inhaled and nasally applied steroids, as well as topical steroids outside the vaccination area are permitted
• Any medically diagnosed or suspected condition of immunodeficiency or medical history thereof
• Known HIV infection
• Any other known infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patients' blood or tissue. Examples are: rabies, Mycobacterium leprae, Plasmodium falciparum, Coccidiodes immitis
• Acute and active infections requiring oral or intravenous antibiotics, antiviral or antifungal therapy within 30 days prior to signing of the IC 2 by the patient (exception: Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infections; direct-acting antivirals may be applied as medically indicated.)
• Patients undergoing renal dialysis or with relevant chronic renal failure
• Abnormal laboratory values as specified below:
• Hematology: Hemoglobin (\< 8.5 g/dl), platelets (\< 75,000/µl), leukocytes (\< 2,500/µl), neutrophils (\< 1,000/µl), lymphocytes (\< 500/µl)
• Liver function: serum bilirubin (≥ 3 x ULN), Alanine aminotransferase (ALAT) or Aspartate aminotransferase (ASAT) (≥ 5 x ULN)
• Renal function: serum creatinine (≥ 1.5 x ULN)

Sponsors & Collaborators

• National Cancer Institute, Naples: lead
• Immatics Biotechnologies GmbH: collaborator
• CureVac: collaborator
• European Commission: collaborator

Study Sites (6)

Universitair Ziekenhuis Antwerpen (UZA), Division of Gastroenterology and Hepatology

Edegem, 2650, Belgium

Location

Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie

Tübingen, 72076, Germany

Location

Istituto Nazionale Tumori "Pascale" (INTNA)

Napoli, 80131, Italy

Location

Ospedale Sacro Cuore-Don Calabria U.O.C. Oncologica Medica

Negrar, 37024, Italy

Location

Universidad de Navarra (NAVAR), Internal Medicine

Pamplona, 31008, Spain

Location

The University of Birmingham, School of Immunity and Infection, College of Medical and Dental Science (BHAM)

Birmingham, B152TT, United Kingdom

Location

Related Publications (1)

• Loffler MW, Gori S, Izzo F, Mayer-Mokler A, Ascierto PA, Konigsrainer A, Ma YT, Sangro B, Francque S, Vonghia L, Inno A, Avallone A, Ludwig J, Alcoba DD, Flohr C, Aslan K, Mendrzyk R, Schuster H, Borrelli M, Valmori D, Chaumette T, Heidenreich R, Gouttefangeas C, Forlani G, Tagliamonte M, Fusco C, Penta R, Inarrairaegui M, Gnad-Vogt U, Reinhardt C, Weinschenk T, Accolla RS, Singh-Jasuja H, Rammensee HG, Buonaguro L. Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma. Clin Cancer Res. 2022 Jun 13;28(12):2555-2566. doi: 10.1158/1078-0432.CCR-21-4424.

  PMID: 35421231 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Cyclophosphamide

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

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

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 29, 2017
• Study Start: September 18, 2017
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); GB (1); IT (2); DE (1); ES (1)