Pembrolizumab + Lenvatinib for Advanced Cancers with Brain Metastases
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must not be taking: Anticoagulants, Corticosteroids
Disqualifiers: Hepatocellular carcinoma, Spinal cord compression, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a single-center, open-label, multi-cohort Phase II study evaluating the efficacy and safety of pembrolizumab in combination with lenvatinib in patients with solid tumors and brain metastases.
The study will be comprised of 3 patient cohorts: triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and solid tumor types other than TNBC and NSCLC. Cohort 3 will be comprised of solid tumor types with established (e.g., renal cell carcinoma \[RCC\], endometrial cancer) or preliminary clinical evidence (e.g., gastric cancer, colorectal cancer) of efficacy of programmed cell death-1 (PD-1) and angiogenesis inhibitors. The study will be conducted using a Simon's optimal two-stage design, and approximately 87 patients will be enrolled concurrently (n=29 per cohort).
The primary endpoint is intracranial objective response rate (ORR) as assessed by the modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not be on certain treatments like systemic steroids above a specific dose or have received certain therapies recently. It's best to discuss your current medications with the study team to see if any adjustments are needed.
What data supports the effectiveness of the drug combination of pembrolizumab and lenvatinib for advanced cancers with brain metastases?
Research shows that the combination of pembrolizumab and lenvatinib has demonstrated strong anti-tumor activity and lasting responses in various advanced solid tumors, including gastric cancer and melanoma, suggesting potential effectiveness for other cancers as well.
12345Is the combination of pembrolizumab and lenvatinib generally safe for humans?
The combination of pembrolizumab and lenvatinib has been studied in various cancers and generally shows a manageable safety profile. Common side effects include high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.
36789How is the drug combination of pembrolizumab and lenvatinib unique for treating advanced cancers with brain metastases?
The combination of pembrolizumab and lenvatinib is unique because it combines an immune checkpoint inhibitor (pembrolizumab) that helps the immune system attack cancer cells, with a multikinase inhibitor (lenvatinib) that blocks signals promoting tumor growth. This dual approach has shown promising results in other cancers, suggesting potential benefits for advanced cancers with brain metastases, where standard treatments are limited.
14101112Eligibility Criteria
Adults with certain types of cancer (TNBC, NSCLC, or other solid tumors) that have spread to the brain. They must have good kidney function, controlled blood pressure, and no serious liver issues. Patients should not be pregnant or breastfeeding and must agree to use contraception. Those with specific lung cancer mutations or untreated spinal cord compression are excluded.Inclusion Criteria
Patients must provide written informed consent
Hepatitis B and C screening tests are required under specific conditions
I have brain metastases with little to no symptoms.
+9 more
Exclusion Criteria
I have taken specific medications before.
I have an immune system disorder or I am on long-term steroids.
I have untreated spinal cord compression or cancer spread to the lining of my brain.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive pembrolizumab in combination with lenvatinib for solid tumors and brain metastases
12 weeks
Bi-weekly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
8 weeks
Monthly visits (in-person)
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The trial is testing the combination of Pembrolizumab (an immunotherapy drug) and Lenvatinib (a medication that inhibits tumor blood vessel growth) in patients with different cancers that have metastasized to the brain. The goal is to see how well this combo works on brain tumors using a two-stage study design.
3Treatment groups
Experimental Treatment
Group I: Cohort 3Experimental Treatment2 Interventions
Patients with other solid tumor types and brain metastases
Group II: Cohort 2Experimental Treatment2 Interventions
Patients with NSCLC and brain metastases
Group III: Cohort 1Experimental Treatment2 Interventions
Patients with TNBC and brain metastases
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
Eisai Inc.Industry Sponsor
References
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.
Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. [2023]Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).
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).
Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. [2023]The combination of pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor, shows synergistic activity in preclinical and clinical studies in solid tumours. We assessed the clinical activity of this combination therapy in patients with pleural mesothelioma who progressed after platinum-pemetrexed chemotherapy.
Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. [2021]Modulation of vascular endothelial growth factor-mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. We report results from the dose-finding and initial phase II expansion of a phase Ib/II study of lenvatinib plus pembrolizumab in patients with selected advanced solid tumors.
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.
Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. [2023]Lenvatinib plus pembrolizumab showed significantly improved progression-free and overall survival outcomes compared with sunitinib in patients with advanced renal cell carcinoma in the CLEAR study (NCT02811861). Here, we used CLEAR data to characterize common adverse reactions (ARs; adverse-event preferred terms grouped in accordance with regulatory authority review) associated with lenvatinib plus pembrolizumab and review management strategies for select ARs.
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.
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).
Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. [2022]Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.
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.
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.