Pembrolizumab + Lenvatinib for Advanced Cervical Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen bySamir Khleif, MD
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Georgetown University
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Pregnancy, Active infection, CNS metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a phase II trial of combination therapy of pembrolizumab and lenvatinib in patients with locally advanced or metastatic cervical cancer that had failed first line of therapy. The hypothesis is the combination of lenvatinib and pembrolizumab will overcome vascular endothelial growth factor (VEGF)-mediated immunosuppression to enhance the response of patients with locally advanced or metastatic cervical cancer.
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, it mentions that participants should not be on certain therapies like systemic steroids or immunosuppressive drugs shortly before starting the trial. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination Pembrolizumab and Lenvatinib for advanced cervical cancer?
Research shows that Pembrolizumab, when used alone, has shown promise in treating advanced cervical cancer, with some patients experiencing prolonged response and stable disease. Additionally, the combination of Pembrolizumab and Lenvatinib has demonstrated effectiveness in treating other types of advanced cancers, such as endometrial cancer, suggesting potential benefits for cervical cancer as well.
12345Is the combination of pembrolizumab and lenvatinib generally safe for humans?
The combination of pembrolizumab and lenvatinib has been studied in patients with endometrial cancer, and the safety profile is generally consistent with each drug used alone. Common side effects include high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, tiredness, and weight loss.
678910How is the drug combination of pembrolizumab and lenvatinib unique for treating advanced cervical cancer?
The combination of pembrolizumab and lenvatinib is unique because it pairs an immune checkpoint inhibitor (pembrolizumab) with a multikinase inhibitor (lenvatinib), potentially offering a novel approach to treating advanced cervical cancer by targeting both the immune system and cancer cell growth pathways.
23111213Eligibility Criteria
This trial is for women at least 18 years old with advanced cervical cancer that worsened after first-line therapy. They must have measurable disease, provide a tumor tissue sample, and have proper organ function. Women of childbearing potential must agree to contraception guidelines. Exclusions include severe allergies to the drugs tested, recent other treatments or vaccines, certain health conditions like uncontrolled blood pressure or active infections.Inclusion Criteria
I am fully active or restricted in physically strenuous activity but can do light work.
Absolute neutrophil count (ANC) ≥1500/µL
My organs are functioning well, tested within the last 28 days.
+14 more
Exclusion Criteria
I have a history of Hepatitis B or active Hepatitis C.
I do not have serious heart problems like recent heart attacks or severe heart failure.
My brain metastases are stable, and I haven't needed steroids for 14 days.
+22 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive pembrolizumab and lenvatinib combination therapy. The treatment is administered in cycles, with each cycle lasting 21 days.
up to 2 years
Day 1 of each cycle (each cycle is 21 days)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including evaluation of overall survival and progression-free survival.
up to 2 years
Every 12 weeks after end of treatment
Participant Groups
The trial tests pembrolizumab combined with lenvatinib in patients with advanced cervical cancer who didn't respond well to initial treatment. It's believed this combo could counteract VEGF-mediated immunosuppression and improve patient response.
1Treatment groups
Experimental Treatment
Group I: Pembrolizumab with LenvatinibExperimental Treatment2 Interventions
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:
Georgia Cancer Center at Augusta UniversityAugusta, GA
MedStar Georgetown University HospitalWashington, United States
John Theurer Cancer Center at Hackensack UMCHackensack, NJ
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Who Is Running the Clinical Trial?
Georgetown UniversityLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. [2021]Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors.
Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma. [2022]To investigate the efficacy of pembrolizumab plus lenvatinib as a second-line or later-line therapy in women with advanced or recurrent uterine carcinosarcoma (UCS).
Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. [2022]Pembrolizumab plus lenvatinib is a novel combination with promising efficacy in patients with advanced and recurrent endometrial cancer. This combination demonstrated high objective response rates in a single-arm phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with advanced endometrial cancer (KEYNOTE-146/Study 111) after ≤2 previous lines of therapy. In a randomized phase 3 trial of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in patients with advanced endometrial cancer (KEYNOTE-775/Study 309), after 1‒2 previous lines of therapy (including neoadjuvant/adjuvant), this combination improved objective response rates, progression-free survival, and overall survival compared with chemotherapy.
Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer. [2020]Optimal treatment for advanced cervical cancer after first line chemotherapy remains undefined. Immune checkpoint inhibition with pembrolizumab, a programmed cell death protein 1(PD-1) inhibitor, is under investigation. We analyzed the micro-environmental and molecular genetic profile of tumors from 4 patients with metastatic cervical cancer treated with off-label second-line pembrolizumab in an effort to identify predictive biomarkers. All patients received 2 mg/kg of pembrolizumab, 3-weekly until disease progression. Immunohistochemistry(IHC) for PD-1, PD-L1, CD3 and CD8, as well as next generation sequencing (NGS) for 50 cancer-related genes were performed on tumor samples. All patients tolerated treatment well with no discontinuation of treatment due to toxicity. One patient experienced dramatic and prolonged partial response, and remains stable on pembrolizumab with a progression free survival (PFS) of 21 months at the time of reporting of this series. Three patients experienced disease progression as best response. In the exceptional responder, there was no tumoral expression of PD-L1, however, combined positive score (CPS) for PD-L1 was 1 and we identified somatic mutations in ERBB4(R612W), PIK3CA(E542K) and RB1(E365K). In 2 patients, despite progressive disease defined by RECIST v1.1, symptom stabilization on pembrolizumab was observed. The tumors of both patients had PD-1 expression in ≥1% of stromal lymphocytes. All patients with response or clinical benefit had CPS for PD-L1 ≥ 1. NGS revealed PIK3CA mutations in 3 tumors. Pembrolizumab is a promising therapeutic option in advanced cervical cancer. Further evaluation of biomarkers may guide optimal patient selection.
Immunotherapy and targeted therapy for cervical cancer: an update. [2016]The prognosis of patients with metastatic cervical cancer is poor with a median survival of 8-13 months. Despite the potency of chemotherapeutic drugs, this treatment is rarely curative and should be considered palliative only. In the last few years, a better understanding of Human papillomavirus tumor-host immune system interactions and the development of new therapeutics targeting immune check points have renewed interest in the use of immunotherapy in cervical cancer patients. Moreover, next generation sequencing has emerged as an attractive option for the identification of actionable driver mutations and other markers. In this review, we provide background information on the molecular biology of cervical cancer and summarize immunotherapy studies, targeted therapies, including those with angiogenesis inhibitors and tyrosine kinase inhibitors recently completed or currently on-going in cervical cancer patients.
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.
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 in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. [2023]Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation.
Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab. [2022]The combination of lenvatinib plus pembrolizumab has shown efficacy in treatment of advanced endometrial carcinoma (that is not microsatellite instability-high or mismatch repair deficient) following prior systemic therapy in any setting in the open-label, single-arm, phase Ib/II Study 111/KEYNOTE-146. With the exception of hypothyroidism, the safety profile of the combination was comparable to that of each monotherapy. Given the medical complexity and fragility of patients with endometrial carcinoma, further characterization of adverse reactions (ARs) associated with treatment will help health care professionals to optimize treatment with lenvatinib plus pembrolizumab combination therapy.
Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer. [2022]We reviewed our institutional data to evaluate toxicity and efficacy outcomes of pembrolizumab/lenvatinib in recurrent endometrial cancer in a "real-world" clinical setting and to compare the impact of reduced lenvatinib starting dose on outcomes.
Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. [2021]There are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.
Pembrolizumab for advanced cervical cancer: safety and efficacy. [2021]Introduction: Pembrolizumab is an immune checkpoint inhibitor with high specificity for binding to the programmed cell death 1 (PD-1) receptor. It has been approved by the FDA in patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express the programmed cell death ligand 1 (PD-L1).Areas covered: Clinical studies of pembrolizumab in cervical cancer were analyzed and discussed. Data were obtained by searching for English peer-reviewed articles on PubMed, clinical trials registered on clincaltrials.gov and related abstracts on the ASCO meeting library. The aim was to review the status of pembrolizumab, the published and ongoing trials, and its safety and efficacy.Expert opinion: Pembrolizumab may ultimately represent a treatment of choice for advanced cervical cancer with PD-L1 expression, both in metastatic and recurrent setting. However, it is essential to better identify and characterize patients that will benefit the most.
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.