Neoantigen Dendritic Cell Vaccine and Nivolumab in HCC and Liver Metastases From CRC

NCT04912765 | Recruiting Phase 2

• 1 other identifier: CA209-7R9
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm phase II study of adjuvant intra-dermal NA DC vaccine combined with intravenous nivolumab in patients with resectable HCC (group A) or CRLM (group B) planned for curative surgery (with/without local ablation).

Conditions

Hepatocellular Carcinoma; Hepatocellular Cancer; Colorectal Cancer; Colorectal Carcinoma; Liver Metastases

Keywords

Tumour neoantigens; Tumor neoantigens; Cancer vaccine; Colorectal Cancer; Hepatocellular Cancer; Immunotherapy; anti-PD1

Outcome Measures

Primary Outcomes (2)

• 24-month Relapse Free Survival

  To investigate the clinical efficacy of combining NA DC vaccine with nivolumab in resected HCC and resected CRLM patients.

  Time from liver resection to first documented disease recurrence or death by any cause, up to 2 years

• Induced immune response against vaccinated NAs

  To determine the presence of NA specific T cells in resected HCC and resected CRLM patients after vaccination. Assessed by EPISOT and/or intracellular cytokine staining (ICS) assay with NA peptides in post-vaccination peripheral blood mononuclear cells (PBMC) compared to pre-vaccination PBMCs.

  Time from liver resection to first documented disease recurrence or death by any cause, up to 2 years

Secondary Outcomes (2)

• Frequency and severity of treatment-emergent adverse events (AE)

  From the time of start of first treatment administered until 100 days after last dose of study treatment

• Overall Survival

  From time of start of study enrolment to death due to any cause, up to 7 years

Study Arms (1)

Neoantigen Dendritic Cell Vaccine and Nivolumab

EXPERIMENTAL

NA DC vaccine every 2 weeks at a dose of 3-5 million cells. Adjuvant nivolumab every 2 weeks at 240mg when given concurrently with the vaccine; every 4 weeks at 480mg after vaccine treatment is completed for a total duration of 1 year.

Biological: Neoantigen Dendritic Cell Vaccine; Drug: Nivolumab

Interventions

Neoantigen Dendritic Cell Vaccine BIOLOGICAL

10 doses of the vaccine will be administered via intra-dermal injection concurrently with adjuvant nivolumab.

Neoantigen Dendritic Cell Vaccine and Nivolumab

Nivolumab DRUG

9 doses of 240mg IV nivolumab as a 30 minutes infusion will be administered in combination with NA DC vaccine starting from the second vaccine dose. Upon completion of 10 doses of NA DC vaccine, 480mg IV nivolumab will be administered as a 30 minutes infusion for a maximum of 9 doses.

Also known as: Opdivo

Neoantigen Dendritic Cell Vaccine and Nivolumab

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HCC specific criteria (Group A):
• Participants must have either newly diagnosed or recurrent HCC, confirmed by histology/cytology or clinically by AASLD criteria in cirrhotic subjects amenable for management with curative intent by resection (with or without the addition of local ablation), if they fulfil the following radiological criteria.
• Up to three tumours, at least one with a diameter \> 3cm
• More than three tumours, none with a diameter \> 5 cm
• Recurrent HCCs are permitted if they were previously treated with curative intent (e.g. by surgery or ablative methods) and with liver-limited recurrence fulfilling criteria (a) and (b)
• Child-Pugh Score 5 or 6
• All participants are required to have imaging studies (CT chest, tri-phasic CT/MRI of the liver, contrast-enhanced CT/MRI of abdomen and pelvis and other suspected/known sites of disease, and bone scans if indicated) confirming no-extra-hepatic metastatic disease within 12 weeks prior to study enrolment.
• CRLM specific criteria (Group B):
• Patients with histologically- or cytologically-diagnosed colorectal cancer with liver-limited metastases are eligible to enrol if:
• There are no other sites of metastases aside from the liver confirmed by imaging studies (contrast-enhanced CT chest, abdomen and pelvis or contrast-enhanced CT chest and MRI abdomen and pelvis and other suspected sites of disease, and bone scans if indicated) at least 12 weeks prior to study enrolment AND
• The liver metastases are amenable and planned for curative surgical resection with or without the addition of local ablation AND
• The primary colorectal tumour had previously been resected or is amendable and planned for surgical resection.
• Participants must have received peri-operative chemotherapy or are being planned for adjuvant chemotherapy after curative surgical resection
• Participants with rectal cancer who received neoadjuvant radiation or are planned for adjuvant radiation are allowed into the study.
• Participants are eligible to enroll if they have non-viral related-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:

You may not qualify if:

• HCC specific criteria (Group A):
• Target Disease Exceptions
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Any evidence of tumour metastasis or co-existing malignant disease.
• Participants showing evidence of macrovascular invasion on imaging tests.
• Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation.
• Participants previously receiving any prior systemic therapy, trans-arterial embolization or chemoembolisation (TAE/TACE), selective internal radiation therapy (SIRT) and stereotactic radiation therapy (SBRT) for HCC.
• CRLM specific criteria (Group B)
• Target Disease Exceptions a) Patients with extra-hepatic colorectal metastases.
• Medical Conditions
• Active co-infection with:
• Both hepatitis B and C as evidenced by detectable HBV surface antigen (HBs Ag) or HBV DNA and HCV RNA, OR
• Hepatitis D infection in participants with hepatitis B
• Known positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

National Cancer Center Singapore

Singapore, 169690, Singapore

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms; Colorectal Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

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

• Si Lin Koo

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Si Lin Koo

CONTACT

+65 6436 8000; koo.si.lin@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 3, 2021
• Study Start: April 15, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

SG (1)