Pembrolizumab + Lenvatinib for Gastric Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Immunosuppressants, Steroids
Disqualifiers: Immunodeficiency, Cardiovascular impairment, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This early phase I trial studies the effect of pembrolizumab and lenvatinib in treating patients with gastroesophageal adenocarcinoma that has spread to other places in the body (advanced/metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and lenvatinib may kill more tumor cells.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.
What data supports the effectiveness of the drug combination of pembrolizumab and lenvatinib for gastric cancer?
Research shows that pembrolizumab, when used alone, helps about 15% of patients with advanced gastric cancer. Lenvatinib has been found to enhance the effectiveness of pembrolizumab by reducing certain immune cells that help tumors grow and increasing other immune cells that fight tumors. Together, these drugs have shown promising results in treating various cancers, including gastric cancer.
12345Is the combination of pembrolizumab and lenvatinib generally safe for humans?
The combination of pembrolizumab and lenvatinib has been studied in various cancers, showing a safety profile consistent with known side effects of each drug. Common side effects include high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, tiredness, and weight loss.
36789What makes the drug combination of pembrolizumab and lenvatinib unique for treating gastric cancer?
The combination of pembrolizumab and lenvatinib is unique for treating gastric cancer because it combines an immune checkpoint inhibitor (pembrolizumab) with a multikinase inhibitor (lenvatinib), which together enhance the body's immune response against cancer cells and reduce tumor-associated immune cells, potentially improving treatment effectiveness compared to using each drug alone.
123410Eligibility Criteria
This trial is for adults with advanced or metastatic gastroesophageal adenocarcinoma that's inoperable and hasn't responded to standard treatments. Participants must have acceptable organ function, controlled blood pressure, no major surgery within 3 weeks before the trial, not be pregnant or breastfeeding, and agree to use effective contraception.Inclusion Criteria
Subject (or legally acceptable representative if applicable) provides written informed consent for the trial
Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or EPO dependency
AST and ALT =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases
+15 more
Exclusion Criteria
Currently participating in or has participated in a study of an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment
Known psychiatric or substance-abuse disorders that would interfere with cooperation with trial requirements
I have cancer that has spread to my brain or surrounding membranes.
+25 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive pembrolizumab intravenously on day 1 and lenvatinib orally once daily. Treatment repeats every 42 days for up to 17 cycles.
Approximately 71 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment completion
Every 12 weeks
1 visit at 30 days post-treatment, then every 12 weeks
Participant Groups
The study tests pembrolizumab (an immunotherapy drug) combined with lenvatinib (a drug blocking enzymes needed by cancer cells). It aims to see if this combination can better attack the cancer and halt its growth compared to current methods.
1Treatment groups
Experimental Treatment
Group I: Treatment (pembrolizumab, lenvatinib)Experimental Treatment2 Interventions
Patients receive pembrolizumab IV over 30 minutes on day 1 and lenvatinib PO QD, Treatment repeats every 42 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.
Lenvatinib is already approved in United States, European Union, European Union for the following indications:
🇺🇸 Approved in United States as Lenvima for:
- Differentiated Thyroid Cancer
- Renal Cell Carcinoma
- Hepatocellular Carcinoma
- Endometrial Cancer
🇪🇺 Approved in European Union as Lenvima for:
- Thyroid Cancer
- Renal Cell Carcinoma
- Hepatocellular Carcinoma
- Endometrial Cancer
🇪🇺 Approved in European Union as Kisplyx for:
- Renal Cell Carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. [2023]Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).
Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. [2021]Both pembrolizumab and lenvatinib demonstrate antitumor activity and safety in cancers. However, whether their combination is safer and more effective than monotherapies remains unknown. A systematic review was performed to assess the safety and efficacy of pembrolizumab plus lenvatinib versus their respective monotherapies in solid cancers.
Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. [2020]Pembrolizumab, an anti-PD-1 antibody, results in tumour response in around 15% of patients with advanced gastric cancer who have a PD-L1 combined positive score of at least 1. Lenvatinib, a multikinase inhibitor of VEGF receptors and other receptor tyrosine kinases, substantially decreased tumour-associated macrophages and increased infiltration of CD8 T cells, resulting in enhanced anti-tumour activity of PD-1 inhibitors in an in-vivo model. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced gastric cancer in a phase 2 study.
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. [2020]Lenvatinib is a multikinase inhibitor of VEGFR1, VEGFR2, and VEGFR3, and other receptor tyrosine kinases. Pembrolizumab, an antibody targeting PD-1, has moderate efficacy in biomarker-unselected endometrial cancer. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced endometrial carcinoma, after establishing the maximum tolerated dose in a phase 1b study.
The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]Tumor progression and immune evasion result from multiple oncogenic and immunosuppressive signals within the tumor microenvironment. The combined blockade of VEGF and inhibitory immune checkpoint signaling has been shown to enhance immune activation and tumor destruction in preclinical models. The LEAP clinical trial program is evaluating the safety and efficacy of lenvatinib (a multikinase inhibitor) plus pembrolizumab (a PD-1 inhibitor) across several solid tumor types. Preliminary results from ongoing trials demonstrate robust antitumor activity and durable responses across diverse tumor types with a manageable safety profile. Thus, lenvatinib plus pembrolizumab is anticipated to be an important potential new regimen for several solid cancers that currently have limited therapeutic options. Clinical trial registration: NCT03884101, NCT03713593, NCT03820986, NCT03776136, NCT03797326, NCT03829319, NCT03829332, NCT03976375, NCT04428151, NCT04199104, NCT03898180, NCT04246177 (ClinicalTrials.gov).
Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]To evaluate adverse events (AEs) of combination lenvatinib plus pembrolizumab for the treatment of recurrent endometrial cancer (EC) and to assess outcomes by lenvatinib starting dose.
Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma. [2022]Lenvatinib combined with pembrolizumab showed a promising result in an early phase study for hepatocellular carcinoma (HCC). The efficacy and safety of lenvatinib plus pembrolizumab for patients with unresectable HCC (uHCC) beyond the first-line setting were unclear.
Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]The combination of lenvatinib plus pembrolizumab demonstrated a relevant clinical benefit in patients with endometrial carcinoma. The safety profile was consistent with the established profiles of each drug in monotherapy, with the most frequent adverse events being hypertension, an on-target effect, hypothyroidism, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.
Combined use of pembrolizumab and lenvatinib: A review. [2023]The purpose of this article is to review the pharmacology, safety, evidence for current use, and potential futures uses for combination therapy with pembrolizumab and lenvatinib.
A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. [2022]Combination treatment using lenvatinib (a multikinase inhibitor) plus pembrolizumab (a programmed death-1 immune checkpoint inhibitor) has shown efficacy in the treatment of endometrial and renal cell cancers. This phase 1b study investigated the tolerability and safety of lenvatinib plus pembrolizumab in Japanese patients with metastatic selected solid tumors.