IMMULAB - Immunotherapy With Pembrolizumab in Combination With Local Ablation in Hepatocellular Carcinoma (HCC)

NCT03753659 | Completed Phase 2 Results DMC

• 1 other identifier: IMMULAB
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, single arm, prospective, open-label phase II trial investigating the clinical activity of peri-interventional treatment with the anti-PD1 antibody pembrolizumab in HCC patients who are candidates for local ablation via either radiofrequency ablation (RFA) or microwave ablation (MWA) or brachytherapy or combination of TACE with RFA, MWA or brachytherapy.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Hepatocellular carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) According to RECIST 1.1

  Evaluation of ORR according to RECIST 1.1 after two cycles of pembrolizumab and before performing local ablation will allow testing of the hypothesis that pre-interventional treatment with pembrolizumab before local ablation will result in conversion / downstaging of borderline candidates for local ablation. Furthermore, ORR is generally accepted as a valid endpoint for efficacy evaluation in one-armed trials without control group. Criteria used for this Outcome Measure: Percentage of patients with complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target and non-target lesions assessed by radiological imaging: Complete Response (CR): Disappearance of all lesions; Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions and no new non-target lesions and no progression in non-target-lesions. Overall Response (OR) = CR + PR.

  After 6 weeks (2 cycles) of treatment

Secondary Outcomes (5)

• Time to Recurrence (TTR) According to RECIST 1.1

  18 months of Follow Up

• Recurrence Free Survival According to RECIST 1.1

  18 months of Follow Up

• Overall Survival (OS)

  18 months of Follow Up

• Incidence and Severity of Adverse Events: Number of Patients With at Least One AE Reported

  Time period beginning at first administration of study drug (maximum 12 months of treatment) through 110 days after last administration, or 30 days following last administration of study drug if the participant initiates new anticancer therapy

• Identification of Molecular Biomarkers in Tumor Tissue and Blood Samples by Immunohistochemical and Molecular Analyses in a Central Lab

  9 weeks of treatment

Study Arms (1)

Pembrolizumab with local ablation

EXPERIMENTAL

* Pembrolizumab 200mg IV Q3W on day 1 of cycle 1 and 2 * Radio Frequency Ablation (RFA) / Microwave Ablation (MWA) / brachytherapy or combination of TACE with RFA, MWA or brachytherapy will be performed on day 1 of cycle 3 * Pembrolizumab 200mg IV administration 2 days after local ablation * Pembrolizumab 200mg IV Q3W for up to 12 months total treatment duration

Drug: Pembrolizumab; Procedure: Radio Frequency Ablation (RFA); Procedure: Microwave Ablation (MWA); Radiation: Brachytherapy; Drug: Transarterial Chemoembolisation (TACE)

Interventions

Radio Frequency Ablation (RFA) PROCEDURE

Local ablation via RFA will be performed via ultrasound- or CT-guided placement of a needle electrode / probe penetrating into the lesion center

Also known as: Study treatment

Pembrolizumab with local ablation

Microwave Ablation (MWA) PROCEDURE

Local ablation via MWA will be performed via ultrasound- or CT-guided placement of a needle electrode / probe penetrating into the lesion center

Also known as: Study treatment

Pembrolizumab with local ablation

Brachytherapy RADIATION

Local ablation via brachythwerapy will be performed via ultrasound- or CT-guided placement of a needle electrode / probe penetrating into the lesion center

Also known as: Study treatment

Pembrolizumab with local ablation

Transarterial Chemoembolisation (TACE) DRUG

According to Investigator's choice, TACE using drug eluting beads can be performed combined with RFA, MWA or brachytherapy

Also known as: Study treatment

Pembrolizumab with local ablation

Pembrolizumab DRUG

IV infusion

Also known as: Study treatment

Pembrolizumab with local ablation

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of HCC
• Has a Child-Pugh Classification score ≤ 6 for assessed liver function within 7 days before allocation (Appendix 4: Child-Pugh Score)
• Candidate for local ablation (via either RFA or MWA or brachytherapy or combination of TACE with RFA, MWA or brachytherapy \[ablation technique according to Investigator's choice\]), i.e.:
• According to Investigator's assessment an R0 state can be obtained after a maximum of two RFA/MWA interventions (initial ablation + one additional re-ablation at maximum).
• Patients (including high risk patients) with: :
• Presence of ≤ 5 tumor nodules with diameters ≤ 7cm \[longest axis\] each OR
• Vascular infiltration
• Has received no prior systemic therapy for HCC NOTE: Patients who have received prior local therapy by transarterial chemoembolization (TACE) are not excluded if TACE has been performed \>8 weeks before study allocation.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously treated (e.g. irradiated or subject to TACE) area are considered measurable if vital tumor has been demonstrated by contrast enhanced imaging in such lesions\*.
• Male/female participants who are at least 18 years of age on the day of signing informed consent will be enrolled in this study.
• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
• A male participant with female partner of childbearing potential is eligible to participate if he agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

You may not qualify if:

• Extrahepatic disease
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Presence of tumor thrombus involving main trunk of portal vein
• Has at Screening and/or has had any prior history of Grade ≥ 2 hepatic encephalopathy
• Has at Screening pericardial effusion, uncontrollable pleural effusion, or clinically significant ascites defined as meeting either of (a) detectable ascites on Screening physical examination OR (b) has at Screening ascites requiring paracentesis
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-Programmed death-ligand 1 (anti-PD-L1), or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or at least 5 half-lives of the respective drug/IMP (whichever is longer) prior to allocation.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 4 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine within 4 weeks or for a period of at least 5 half-lives of the respective drug/IMP (whichever is longer) before Screening and during Screening for this trial prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks or for a period of at least 5 half-lives of the respective drug/IMP (whichever is longer) before Screening and during Screening for this trial.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or at least 5 half-lives of the respective drug/IMP (whichever is longer) after the last dose of the previous investigational agent.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (1)

Hannover Medical School

Hanover, Lower Saxony, 30625, Germany

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab; Pharmaceutical Preparations; Radiofrequency Ablation; Brachytherapy

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)

Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative; Radiotherapy

Results Point of Contact

• Title: Prof. Dr. med. Salah-Eddin Al-Batran
• Organization: Frankfurter Institut für Klinische Krebsforschung IKF GmbH

immulab@ikf-khnw.de

0049 69 7601

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Immunotherapy with pembrolizumab in combination with local ablation

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 27, 2018
• Study Start: May 9, 2019
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: March 23, 2026
• Results First Posted: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)