Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Adenocarcinoma

Adenocarcinoma, Clear Cell

Disease Attributes

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Lenvatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Recurrent clear cell carcinoma of gynecological origin (ovarian and endometrial primary) after progression on chemotherapy.

All patients will receive oral lenvatinib daily plus intravenous pembrolizumab 3-weekly.

A cycle is 21 days. Allowances will be made for stepwise dose reductions of lenvatinib due to treatment-related toxicities.

Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, (CTCAE) Version 5.0.

Patients are planned to continue therapy until disease progression, intolerable toxicity, or withdrawal of patient consent.

pembrolizumab and lenvatinib

David Shao Peng Tan

This is a phase II non-randomized, multi-center study. The primary end point of this study is the objective response rate (ORR) at 24 weeks, using response evaluation criteria for solid tumors (RECIST) 1.1 criteria, for the combination therapy of continuous daily oral lenvatinib with three-weekly intravenous pembrolizumab in patients with recurrent clear cell carcinoma of gynecological origin (CCGC). The statistical design is Simon's minimax two-stage design and the present study aims to complete stage 1 of the Simon's two-stage design.

Primary Objective

(1) Objective: To determine the efficacy as measured by the objective response rate (ORR) at 24 weeks using RECIST 1.1 criteria when patients with recurrent CCGCs are treated with lenvatinib plus pembrolizumab.

Hypothesis: The ORR (complete response plus partial response) at 24 weeks seen in recurrent CCGC patients treated with lenvatinib plus pembrolizumab combination therapy will be improved compared to historical control (hypothesized ORR of 30% with combination therapy compared to historical ORR of ORR of 10% with chemotherapy).

Primary Endpoint: The ORR at 24 weeks using RECIST 1.1 criteria when patients with recurrent CCGCs are treated with lenvatinib plus pembrolizumab.

Secondary Objectives,

1. Objective: To determine the efficacy of lenvatinib plus pembrolizumab in recurrent CCGCs.

   Hypothesis: The ORR by immune RECIST (iRECIST) criteria, progression-free survival (PFS) rate and clinical benefit rate (CBR) (complete response plus partial response plus stable disease) at 24 weeks, as well as duration of response and PFS observed in recurrent CCGC patients treated with lenvatinib plus pembrolizumab combination therapy will be improved compared to historical control.

   Endpoint: To determine the ORR using iRECIST criteria at 24 weeks when patients with recurrent CCGCs are treated with lenvatinib plus pembrolizumab.

   Endpoint: To assess the duration of response when patients with recurrent CCGCs are treated with lenvatinib plus pembrolizumab.

   Endpoint: To assess the PFS when patients with recurrent CCGCs are treated with lenvatinib plus pembrolizumab.

   Endpoint: To determine the 24 week PFS rate of lenvatinib plus pembrolizumab in this population.

   Endpoint: To determine the CBR at 24 weeks of lenvatinib plus pembrolizumab in this population.
2. Objective: To describe the adverse event (AE) profile of lenvatinib plus pembrolizumab in this patient population.

Exploratory Objectives

1. Clinical Objectives: To evaluate the effect of potential prognostic factors (baseline patient and tumor characteristics, notably: initial performance status, stage at diagnosis and platinum-free interval), on the efficacy of lenvatinib plus pembrolizumab in this population.
2. Translational Objectives: To evaluate the pre- to post-treatment changes in the frequency of tumor-associated macrophages (TAMs) in patients receiving lenvatinib plus pembrolizumab.
3. Translational Objectives: To evaluate the pre- to post-treatment changes in the frequency and gene expression profile of different lymphocyte (e.g. CD4, CD8, Treg, B cells) and myeloid (e.g. DCs, MDSCs) subsets in patients receiving lenvatinib plus pembrolizumab.
4. Translational Objectives: To identify predictive biomarkers of response in patients receiving lenvatinib plus pembrolizumab (e.g. PD-1/PD-L1/VEGF expression).
5. Translational Objectives: To evaluate the pre-to post-treatment changes in the concentration of relevant cytokines/chemokines (e.g.: GM-CSF, G-CSF, VEGFA, IL2, IL12, IL13, IL6, Interferons) in patients receiving lenvatinib plus pembrolizumab.

combination therapy of continuous daily oral lenvatinib with three-weekly intravenous pembrolizumab in patients with recurrent clear cell carcinoma of gynecological origin (CCGC).

Trial of Lenvatinib Plus PembrolizumAb in Recurrent Gynecological Clear Cell Adenocarcinomas (LARA)

Phase II Trial of Lenvatinib Plus PembrolizumAb in Recurrent Gynecological Clear Cell Adenocarcinomas (LARA)

the percentage of subjects with a confirmed CR or PR as per RECIST 1.1 criteria.

time from enrolment to the first documented tumor progression, or death due to any cause whichever occurred first. PFS time of any living patient with no documented progression, or any patient starting other cytotoxic and/or cytostatic therapies, will be censored at the date of last evaluable disease assessment on-study. PFS time of patients with no evaluable disease assessment on-study will be censored at enrollment

This will be measured from the time measurement criteria for CR/PR (whichever is first recorded) are first met until the first date that recurrent or progressive disease is objectively documented.

National University Hospital, Singapore

Digestive System Diseases

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Liver Extracts

Pre-operative Pembrolizumab (200mg IV every 3 weeks) for 2 cycles

Pre-operative Lenvatinib (8 or 12mg PO once daily according to bodyweight \<60gk≥) for 6 weeks

Pre-operative combination of pembrolizumab and lenvatinib at the standard doses and duration as per cohort 1 and 2

Pembrolizumab and Lenvatinib

Michelle Hung

Marain Duggan

Tim Meyer, BSc MBBS PhD FRCP

This is a multicentre randomised 3-arm phase II clinical trial in patients with resectable Hepatocellular Carcinoma (HCC). Sixty patients will be randomized 1:1:1 to 6 weeks of pre-operative therapy with: pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib followed by up to 12 months treatment with post-operative pembrolizumab. The aim of the study is to compare the efficacy of pembrolizumab combined with lenvatinib with that of pembrolizumab and lenvatinib alone in terms of major pathological response in patients with resectable HCC. Major pathological response will be defined by the proportion of patients with less than 10% viable tumour at resection.

Hepatocellular Carcinoma (HCC), or Liver cancer, is the second most common cause of cancer-related death worldwide and is the most rapidly increasing cause of cancer-related death in the West. The only potentially curative options are transplantation, surgical resection and ablation. Both surgical resection and ablation are associated with a high rate of recurrence and 70% of resected patients relapse within 5 years. To date, no standard adjuvant therapies have been approved. Recent studies provide evidence that immunotherapy may address a significant unmet need in the management of HCC.

Furthermore, there is also a rationale for pre-operative therapy which has been shown to be superior to a postoperative treatment approach as supported by pre-clinical studies. The feasibility and outcomes of this approach have recently been reported in the setting of lung cancer. Lenvatinib, an immunotherapy drug, has been approved as a first treatment option in HCC. Pembrolizumab, another immunotherapy treatment has been evaluated as first treatment option in HCC in two clinical trials. The combination of these two drugs has been explored in HCC in early phase trials.

The aim is to compare the efficacy of pembrolizumab (a type of immunotherapy designed to 're-awaken' the immune system) combined with lenvatinib (an anti-cancer drug that is a multiple kinase inhibitor) with that of pembrolizumab and lenvatinib alone in patients with resectable Hepatocellular Carcinoma.

Treatment lasts for up to 18 months. Depending on when patients are recruited, patients will be followed up for a minimum of 1 year and maximum of 3 years, following the end of their post-surgery treatment. It is expected that it will take 24 months to recruit all the patients.

This is a randomised 3-arm phase II clinical trial in patients with resectable HCC. Sixty patients will be randomized 1:1:1 to pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib.

Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)

PRIMER-1 Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)

The primary aim of the study is to test the hypothesis that the combination of pembrolizumab and lenvatinib result in a higher rate of major pathological response than either drug used as a single-agent in patients with resectable hepatocellular carcinoma.

The hypothesis is that the radiological response rate of pembrolizumab and lenvatinib in combination is greater than that of pembrolizumab and lenvatinib as single agents. Measured by RECIST 1.1 and mRECIST performed pre-operatively and compared with pre-treatment baseline imaging)

Relapse free survival at 12 months from surgery

Defined as the proportion of patients with surgery delayed by more than 4 weeks from the planned surgery date due to IMP-related adverse events (AEs) or serious adverse events (SAEs))

based on the Clavien-Dindo classification

measured by the proprtion of patients mpleting protocol defined study-drug intervention.

Incidence and of adverse events (AEs) reported. Events will be classified according to CTCAE V5.0

Merck Sharp & Dohme LLC

University College, London

Rare Diseases

Biliary Tract Neoplasms

Biliary Tract Diseases

Biliary Tract Cancer

Gemcitabine

Oxaliplatin

Antimetabolites

Drug：Pembrolizumab Pembrolizumab 200 mg will be administered intravenously once every three weeks, with intravenous infusion on Day 1 of each cycle. Drug: Lenvatinib Oral Product The dose of lenvatinib is 12mg/day for patients with a body weight of ≥60 kg, and 8mg/day for patients with a body weight of \<60 kg, taken once daily. Drug: Chemotherapy GEMOX regimen: Gemcitabine 1000mg/m2 will be administered intravenously over 30 minutes on Day 1 and Day 8; Oxaliplatin 100mg/m2 will be administered intravenously over 2 hours on Day 1, and the cycle will be repeated every 3 weeks

Drug：Pembrolizumab Pembrolizumab 200 mg will be administered intravenously once every three weeks, with intravenous infusion on Day 1 of each cycle. Drug: Lenvatinib Oral Product The dose of lenvatinib is 12mg/day for patients with a body weight of ≥60 kg, and 8mg/day for patients with a body weight of \<60 kg, taken once daily.

Drug：Pembrolizumab Pembrolizumab 200 mg will be administered intravenously once every three weeks, with intravenous infusion on Day 1 of each cycle. Drug: GEMOX Chemotherapy GEMOX regimen: Gemcitabine 1000mg/m2 will be administered intravenously over 30 minutes on Day 1 and Day 8; Oxaliplatin 100mg/m2 will be administered intravenously over 2 hours on Day 1, and the cycle will be repeated every 3 weeks

Drug: Pembrolizumab Pembrolizumab 200 mg will be administered intravenously once every three weeks, with intravenous infusion on Day 1 of each cycle. Drug: Lenvatinib Oral Product The dose of lenvatinib is 12mg/day for patients with a body weight of ≥60 kg, and 8mg/day for patients with a body weight of \<60 kg, taken once daily. Drug: Chemotherapy GEMOX regimen: Gemcitabine 1000mg/m2 will be administered intravenously over 30 minutes on Day 1 and Day 8; Oxaliplatin 100mg/m2 will be administered intravenously over 2 hours on Day 1, and the cycle will be repeated every 3 weeks.

Pembrolizumab,Lenvatinib and Gemox Chemotherapy（Gemcitabine and Oxaliplatin）

Pembrolizumab and Gemox Chemotherapy（Gemcitabine and Oxaliplatin）

haitao Zhao, Ph.D

Haitao Zhao, Professor

Explore the impact of the first-line application of Pembrolizumab with or without Lenvatinib or chemotherapy, on the survival, disease progression, and drug safety of patients with advanced biliary tract cancers

This trial is a three-arm, randomized, multi-center clinical study. Eligible subjects who meet the study criteria will be screened and randomized in a 1:1:1 ratio to receive treatment with intravenous infusion of Pembrolizumab with or without chemotherapy and oral lenvatinib. The investigators will closely follow up and assess the efficacy and safety of the combined treatment, evaluate the progression-free survival of the subjects until progression occurs, and observe their overall survival as a secondary outcome.

Pembrolizumab With or Without Lenvatinib or Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer

A Phase II, Multicenter, Randomized Study of Pembrolizumab With or Without Chemotherapy or Lenvatinib in First-Line Treatment of Advanced Biliary Tract Cancer

t refers to the proportion of patients whose tumor volume control (shrinkage or enlargement) reaches a predetermined value and can maintain the minimum required duration. According to the RECIST criteria (version 1.1), during the treatment period or within 30 days after the discontinuation of the investigational drug, it is the sum of the percentage of subjects who achieve complete response (CR), partial response (PR), and stable disease (SD)

It refers to the time from the first administration of the regimen to the first occurrence of disease progression or death due to any cause in the subjects.

The time from randomization to death due to any cause in the subjects

It refers to the time from the first report of objective tumor partial or complete response (based on the earlier occurrence) to the first occurrence of disease progression or death in the subjects

The ratio of subjects who achieve complete response (CR) or partial response (PR) or maintain stable disease (SD) .

The percentage of patients who have not experienced disease progression or death due to any cause after receiving the therapy, among the evaluable patients for efficacy.

The percentage of patients who died due to any cause after receiving therapy among all enrolled patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Lenvatinib Plus PembrolizumAb in Recurrent Gynecological Clear Cell Adenocarcinomas (LARA)	NCT04699071	Adenocarcinomas Recurrent Gynec...	pembrolizumab a...	21 Years - 99 Years	National University Hospital, Singapore
Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)	NCT05185739	Hepatocellular ...	Pembrolizumab Lenvatinib Pembrolizumab a...	18 Years -	University College, London
Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)	NCT05185739	Hepatocellular ...	Pembrolizumab Lenvatinib Pembrolizumab a...	18 Years -	University College, London
Pembrolizumab With or Without Lenvatinib or Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer	NCT06230471	Biliary Tract N...	Pembrolizumab,L... Pembrolizumab a... Pembrolizumab a...	18 Years - 80 Years	Peking Union Medical College Hospital
Trial of Lenvatinib Plus PembrolizumAb in Recurrent Gynecological Clear Cell Adenocarcinomas (LARA)	NCT04699071	Adenocarcinomas Recurrent Gynec...	pembrolizumab a...	21 Years - 99 Years	National University Hospital, Singapore
Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)	NCT05185739	Hepatocellular ...	Pembrolizumab Lenvatinib Pembrolizumab a...	18 Years -	University College, London

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