Pembrolizumab and Lenvatinib in Patients With Advanced HCC Who Are Refractory to Atezolizumab and Bevacizumab/ IO-based Therapy

NCT05101629 | Completed Phase 2

• 4 other identifiers: SOLARIS2021-000355-40AIO-HEP-0121/assIKF-t037
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 12

Brief Summary

Patients with advanced HCC, refractory to atezolizumab and bevacizumab /IO-based therapy will be treated with pembrolizumab and lenvatinib. Efficacy of the combination therapy will be assessed by objective reponse rate, progression free survival, overal survival, safety/tolerability.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; HCC

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) according to RECIST 1.1 criteria

  ORR, defined as the percentage of patients with complete response (CR) or partial response (PR) according to RECIST 1.1.

  up to 36 months

Secondary Outcomes (3)

• Progression free survival (PFS)

  up to 36 months

• Overall survival (OS)

  up to 36 months

• Safety and toxicity

  First treatment until 90 days after end of treatment, up to 27 months

Study Arms (1)

Pembrolizumab Lenvatinib

EXPERIMENTAL

Single arm with Pembrolizumab 200 mg over 30 minutes IV infusion on Day 1 every 3 weeks until disease progression or inacceptable toxicity or end of study treatment. Lenvatinib 8 mg for a body weight \< 60 kg and 12 mg for a body weight ≥ 60 kg orally continuously once daily, starting on Day 1 of every 3 week cycle until disease progression or inacceptable toxicity or end of study treatment.

Drug: Pembrolizumab; Drug: Lenvatinib Capsules

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg, IV, over 30 minutes every 3 weeks

Also known as: Keytruda

Pembrolizumab Lenvatinib

Lenvatinib Capsules DRUG

Lenvatinib 8 mg for BW \< 60 kg / 12 mg for BW ≥ 60 kg oral, once daily for 3 weeks

Also known as: Lenvima

Pembrolizumab Lenvatinib

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.
• Have a tumor, not eligible for resection or local ablation.
• Have experienced disease progression under previous ≥ 4 cycles/12 weeks first line IO-based therapy.
• Have a Child-Pugh Classification score ≤ 6 for assessed liver function within 7 days before allocation (Appendix 4)
• Have at least one measurable site of disease based on RECIST 1.1 with spiral CT scan or MRI. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated 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.
• \*There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.
• 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.
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 210 days after the last dose of study treatment and refrain from donating sperm during this period.
• The participant provides written informed consent for the trial.
• Either pre-treatment tumor tissue available
• Newly obtained biopsies are preferred to archived tissue (archived specimen ≤ 6 months may be acceptable).

You may not qualify if:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Have received prior therapy with any TKI.
• 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 24 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.
• Have an ongoing AE (≥Grade 2) from prior systemic anti-cancer therapy including investigational agents or use of an investigational device.
• Note: 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 intervention.
• Have received prior radiotherapy within 2 weeks of start of study intervention. 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-CNS disease.
• Have received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Are currently participating in a study of an investigational agent or an investigational device.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as they have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible.
• Have a diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Have a known additional malignancy that is progressing or has required active treatment within the past 2 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Have severe hypersensitivity (≥ Grade 3) to lenvatinib, pembrolizumab and/or any of its excipients.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Medizinische Hochschule Hannover, Germany, Prof. Dr. Arndt Vogel: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

Location

Charité-Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Universitätsklinikum Gießen und Marburg

Giessen, 35392, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsklinikum Giessen und Marburg

Marburg, 35043, Germany

Location

Klinikum der Universität München

München, 81377, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab; lenvatinib

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

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

• Arndt Vogel, Prof. Dr.

  Medizinische Hoschschule Hannover

  PRINCIPAL INVESTIGATOR

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: October 20, 2021
• First Posted: November 1, 2021
• Study Start: May 11, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (12)