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Hepatocellular CarcinomaPhase 2NCT05101629

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

A Phase 2 study testing Pembrolizumab and Lenvatinib Capsules in people with Hepatocellular Carcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 12 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Pembrolizumab and Lenvatinib Capsules
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
12 sitesGermany
Study dates
11 May 2022to 30 Jun 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).
  • Core or excisional biopsies mandatory (fine needle aspiration and bone metastasis samples are not acceptable).
  • Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
  • If submitting 15 unstained cut slides, newly cut slides should be submitted to the IKF GmbH lab within 14 days from the date slides are cut.
  • OR tumor tissue is not available as e.g., patient has never undergone biopsy or tissue depleted because of prior diagnostic testing
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation.
  • Have a life expectancy of ≥ 12 weeks.
  • Have adequate organ function as defined in the following table (Table 2). Specimens must be collected within 7 days prior to the start of study intervention.
  • Table 2: Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1500/µL Platelets ≥ 75000/µL Hemoglobin ≥ 8.0 g/dLa Renal Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 × ULN OR
  • ≥ 40 mL/min for participant with creatinine levels > 1.5 × institutional ULN Hepatic Total bilirubin ≤ 2 mg/dL OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 2 mg/dL AST (SGOT) and ALT (SGPT) ≤ 5 × ULN Albumin ≥ 3.0 g/dL Pancreatic Amylase ≤ 1.5 × ULN Lipase ≤ 1.5 × ULN Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
  • a Transfusion are permitted to meet criteria. b Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
  • Participants with past or ongoing HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention and HCV viral load must be below the limit of quantification.
  • Participants with controlled hepatitis B will be eligible if they meet the following criteria:
  • Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study intervention.
  • Participants who are positive for anti-hepatitis B core antibody HBc, negative for HBsAg, and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis.
  • Has adequately controlled blood pressure with or without antihypertensive medications, defined as BP ≤ 150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.

Who cannot join

  • 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.
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  • 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.
  • Have a history of congestive heart failure NYHA > Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study treatment, or cardiac arrhythmia requiring medical treatment at Screening
  • Have bleeding or thrombotic disorders or subjects at risk for severe hemorrhage.
  • Note: The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
  • Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Have an active infection requiring systemic therapy (exception: HBV infection - see inclusion criteria).
  • Have a history of Human Immunodeficiency Virus (HIV) (mandatory testing for HIV during screening is required).
  • Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
  • Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
  • Are unable to swallow orally administered medication or have gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Legal incapacity or limited legal capacity.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Germany12 sites

  • Universitätsklinikum Augsburg

    Augsburg, 86156

  • Charité-Universitätsmedizin Berlin

    Berlin, 13353

  • Krankenhaus Nordwest

    Frankfurt, 60488

  • Universitätsklinikum Gießen und Marburg

    Giessen, 35392

  • Universitätsmedizin Göttingen

    Göttingen, 37075

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitätsklinikum Jena

    Jena, 07747

  • Universitätsklinikum Giessen und Marburg

    Marburg, 35043

  • Klinikum der Universität München

    München, 81377

  • Klinikum rechts der Isar der Technischen Universität München

    München, 81675

  • Klinikum Nürnberg

    Nuremberg, 90419

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: A Phase-II Open-label Study of Pembrolizumab and Lenvatinib in Patients With Advanced Stage Hepatocellular Carcinoma Who Are Refractory to Atezolizumab and Bevacizumab/ IO-based Therapy

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.

Read the detailed description

This is a multicenter, single arm, open-label phase II trial investigating the clinical activity of a second-line therapy with the anti-PD-1 antibody pembrolizumab (200 mg IV, q3w) and the multiple receptor tyrosine kinase inhibitor (TKI) lenvatinib (8 mg for BW < 60 kg / 12 mg for BW ≥ 60 kg p.o. QD) in advanced HCC patients who are refractory to atezolizumab and bevacizumab/ IO-based therapy.

The primary objective is to assess the efficacy by objective response rate (ORR) according to RECIST 1.1 criteria.

Secondary objectives are to determine efficacy in terms of progression free survival (PFS), overall survival (OS) as well as safety and toxicity (acc. to NCI-CTC V5.0).

In addition, tissue and serum samples (optional) will be analyzed for molecular biomarkers predictive for ORR, PFS and OS.

32 patients will be enrolled in this trial.

Being tested
Pembrolizumab, Lenvatinib Capsules
Keywords
Hepatocellular Carcinoma, HCC
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

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

  • Lenvatinib CapsulesDrug

    Also called Lenvima

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

Study groups in NCT05101629
Study groupRoleWhat they receive
Pembrolizumab LenvatinibExperimentalSingle 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.
Receives: Drug: Pembrolizumab; Drug: Lenvatinib Capsules

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 36 months

Secondary outcomes (3)

  1. Progression free survival (PFS)

    PFS, defined as time from first dose of study treatment to date of first observed disease progression according to RECIST 1.1 or death from any cause.

    Measured: up to 36 months

  2. Overall survival (OS)

    OS, defined as time from first dose of study treatment to the date of death of any cause.

    Measured: up to 36 months

  3. Safety and toxicity

    Adverse events will be recorded and graded according to NCI-CTC V5.0. Occurrence of (Serious) Adverse Events at any time during the study. Description by nature (Primary System Organ Class and Preferred Term), severity and causal relationship to drug administration.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2021
  2. Study start11 May 2022
  3. Primary completion30 Jun 2025
  4. Study completion30 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05101629
Sponsor's protocol ID
SOLARIS
Other IDs
2021-000355-40, AIO-HEP-0121/ass, IKF-t037
Status last verified
Jul 2025
First submitted
20 Oct 2021
Last updated
23 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Lenvatinib Capsules in people with Hepatocellular Carcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 12 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) according to RECIST 1.1 criteria (time frame: up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05101629.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.

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