Pembrolizumab + Bevacizumab for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Roswell Park Cancer Institute
Must not be taking: Immunosuppressants, Corticosteroids, PARP inhibitors, others
Disqualifiers: Active CNS metastases, Autoimmune disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial tests whether pembrolizumab combined with bevacizumab with or without agonist anti-CD40 CDX-1140 works to shrink tumors in patients with ovarian cancer that has come back (recurrent). Anti-CD40 CDX-1140 works by stimulating certain immune cells within the tumor and, when combined with other immunotherapy treatments, may increase antitumor antibody production. Immunotherapy with monoclonal antibodies, such as pembrolizumab and bevacizumab, may help the body's immune system, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and bevacizumab with anti-CD40 CDX-1140 may decrease symptoms, prolonged survival, and improve quality of life in patients with ovarian cancer.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain treatments like immunosuppressive medications, systemic corticosteroids, or investigational 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 Bevacizumab for ovarian cancer?
Research shows that Bevacizumab, when combined with other chemotherapy drugs, can significantly prolong the time patients with ovarian cancer live without the disease getting worse. Pembrolizumab has shown antitumor activity in patients with advanced ovarian cancer, suggesting potential benefits when used in combination with Bevacizumab.
12345Is the combination of Pembrolizumab and Bevacizumab safe for humans?
Pembrolizumab and Bevacizumab have been studied separately for safety in humans. Pembrolizumab has been evaluated for safety in advanced ovarian cancer, while Bevacizumab has been used in various cancers, including ovarian cancer. Bevacizumab can cause mild side effects like high blood pressure and bleeding, but serious side effects like gastrointestinal issues are rare. Overall, both drugs have been generally safe in clinical trials, but they can have side effects that should be monitored.
16789How is the drug combination of Pembrolizumab and Bevacizumab unique for treating ovarian cancer?
The combination of Pembrolizumab and Bevacizumab for ovarian cancer is unique because it combines an immune checkpoint inhibitor (Pembrolizumab) that helps the immune system attack cancer cells, with an anti-angiogenic drug (Bevacizumab) that prevents the growth of blood vessels that supply tumors, offering a novel approach compared to traditional chemotherapy.
1231011Eligibility Criteria
This trial is for adults over 18 with recurrent ovarian cancer, including serous, endometrioid, or clear cell types. Participants can have had up to three prior treatments and must be expected to live more than six months. They should be relatively active (ECOG status of 0 or 1) and able to undergo a biopsy. Pregnant women are excluded, as well as those with certain medical conditions or severe allergies.Inclusion Criteria
I am 18 years old or older.
I am not pregnant.
I am willing to have a biopsy of my tumor.
+8 more
Exclusion Criteria
Any condition deemed unsuitable by the investigator
I am able to understand and consent to medical procedures.
Known immunodeficiency or active human immunodeficiency virus (HIV)
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Patients receive pembrolizumab and bevacizumab with or without CDX-1140 intravenously every 3 weeks until disease progression or unacceptable toxicity
Up to 2 years
Every 3 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 years
30 days post-treatment, then every 6 months
Participant Groups
The study tests pembrolizumab combined with bevacizumab and possibly anti-CD40 CDX-1140 in patients whose ovarian cancer has returned. It aims to see if this combination can shrink tumors by stimulating the immune system and producing antitumor antibodies.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (pembrolizumab, bevacizumab, CDX-1140)Experimental Treatment5 Interventions
Patients receive pembrolizumab IV over 30 minutes, bevacizumab IV over 30-90 minutes, and CDX-1140 IV over 90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.
Group II: Arm I (pembrolizumab, bevacizumab)Active Control4 Interventions
Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.
Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:
🇪🇺 Approved in European Union as Avastin for:
- Colorectal cancer
- Breast cancer
- Non-small cell lung cancer
- Renal cell carcinoma
- Ovarian cancer
🇺🇸 Approved in United States as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Glioblastoma
- Renal cell carcinoma
- Cervical cancer
- Ovarian cancer
🇯🇵 Approved in Japan as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Breast cancer
- Renal cell carcinoma
- Ovarian cancer
🇨🇦 Approved in Canada as Avastin for:
- Colorectal cancer
- Non-small cell lung cancer
- Breast cancer
- Renal cell carcinoma
- Ovarian cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Roswell Park Cancer InstituteBuffalo, NY
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
Roswell Park Cancer InstituteLead Sponsor
United States Department of DefenseCollaborator
Merck Sharp & Dohme LLCIndustry Sponsor
National Cancer Institute (NCI)Collaborator
Celldex TherapeuticsIndustry Sponsor
References
Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.
Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.
Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. [2019]Bevacizumab (Avastin®) is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumor angiogenesis. In the EU, in adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab (in combination with carboplatin and paclitaxel) is approved for the first-line treatment of advanced disease and (in combination with carboplatin and gemcitabine) is approved for the treatment of patients with first recurrence of platinum-sensitive disease who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. This article summarizes the pharmacology of bevacizumab and reviews the efficacy and tolerability of bevacizumab combination therapy in well-designed clinical studies in these indications. The addition of bevacizumab to first-line carboplatin plus paclitaxel, followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in women with newly-diagnosed advanced disease (GOG-0218 and ICON7 studies). Progression-free survival was also significantly prolonged after second-line treatment with bevacizumab in combination with carboplatin and gemcitabine, followed by maintenance treatment with bevacizumab alone in women with recurrence (≥ 6 months after front-line platinum-based therapy) of platinum-sensitive disease (OCEANS study). Bevacizumab combination therapy had a generally acceptable tolerability profile in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumors. Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer.
Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged ≥65 years from the PAOLA-1/ENGOT-ov25 trial. [2023]The phase III PAOLA-1/ENGOT-ov25 study (NCT02477644) showed that addition of olaparib to bevacizumab maintenance improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer. We evaluated maintenance olaparib plus bevacizumab in older patients in PAOLA-1.
Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report. [2018]Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growthfactor (VEGF), has been approvedfor concurrent treatment with first line chemotherapy in advanced epithelial ovarian cancer.
Experience with bevacizumab in the management of epithelial ovarian cancer. [2015]Müllerian duct adenocarcinomas, in particular epithelial ovarian cancers, continue to represent a major source of female cancer-related morbidity and mortality, despite advances in surgical management and innovations in cytotoxic chemotherapy. Angiogenesis-targeted therapy seems to be appropriate for exploration in these disease processes based on a wealth of evidence from preclinical and molecular epidemiology studies. Bevacizumab is a prototypical agent neutralizing vascular endothelial growth factor (VEGF), a critical angiogenic promoter related to tumor progression, malignant effusions, and prognosis in ovarian cancer. Phase II trials have demonstrated the activity of bevacizumab as a single agent and in combination with other modalities such as low-dose metronomic cyclophosphamide. Historical studies have supported these observations. Unique toxicities have been ascribed to the administration of bevacizumab and other anti-VEGF molecules for patients with this disease and other solid tumors. Although most of these toxicities (such as proteinuria, hypertension, and bleeding) are generally mild, and are either self-limiting or controllable, other adverse effects, though uncommon, may be serious (these include arterial thromboembolism, wound healing complications, and GI perforation or fistulae). Phase III trials are now in progress to determine the role of this drug in primary therapy as an adjunct to platinum-taxane chemotherapy. This article reviews the background and rationale for anti-VEGF therapy of ovarian cancer, summarizes efficacy and safety data from phase II trials and historical studies of bevacizumab in this disease, introduces the implementation of bevacizumab in phase III front-line trials, examines controversial aspects related to anti-VEGF therapy, and proposes future directions regarding bevacizumab and other angiogenic growth factor-targeted therapeutics.
Anti-angiogenic agents in ovarian cancer: past, present, and future. [2023]Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the progression of ovarian cancer through ascites formation and metastatic spread. Bevacizumab (Avastin(®), Genentech; South San Francisco, CA, USA), a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, is the most widely studied anti-angiogenesis agent both across tumor types and specifically in epithelial ovarian cancer. In 2005, single-agent bevacizumab at 15 mg/kg (IV) every 3 weeks was first reported to be active in a case of recurrent high-grade serous ovarian cancer after failing 11th line cytotoxic treatment. Since then, many case series, phase II and phase III trials have confirmed these results leading to regulatory approval in most countries including the US Food and Drug Administration in 2014. Guidelines now give clear recommendations as to when and how bevacizumab should be integrated into the ovarian cancer treatment paradigm. Other anti-VEGF agents such as the VEGF receptor (VEGFR) tyrosine kinase inhibitors have not shown increased activity or reduced toxicity relative to bevacizumab. However, anti-angiogenics other than anti-VEGF/VEGFR agents such as those targeting Angiopoietin-1 and -2 are in development as well as novel combinations with vascular disrupting agents (VDAs), PARP inhibitors and immune checkpoint inhibitors. Clearly, the benefits of anti-angiogenic agents such as bevacizumab must be carefully weighed against the cost and associated toxicities. Although almost all patients with ovarian cancer will receive an anti-angiogenic compound, cures are not increased. Predictive biomarkers are an urgent unmet need.
Bevacizumab and ovarian cancer. [2021]Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that targets vascular endothelial growth factor-A, and is indicated in the treatment of various tumors (colon, lung, renal, and glioblastoma). It has been recently approved for the treatment of ovarian cancer in various countries. This review summarizes the activity and toxicity of bevacizumab in the treatment of ovarian cancer, both as single-agent drug and in combination with cytotoxic chemotherapy. As a single-agent drug, it has shown response rates of 16-21% in the treatment of recurrent ovarian cancer. Two phase III randomized trials have been published evaluating the addition of bevacizumab to standard chemotherapy as front-line treatment of advanced ovarian cancer. In addition, trials evaluating the combination with chemotherapy in recurrent ovarian cancer (platinum-sensitive and platinum-resistant disease) have also been reported. All these trials showed a statistically significant improvement in progression-free survival although no improvement in overall survival has been reported. The main adverse event is hypertension. Other serious, but uncommon adverse events include gastrointestinal perforation as well as renal and central nervous system toxicity.
Independent radiologic review of AURELIA, a phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. [2022]The randomized, open-label, phase 3 Avastin® Use in Platinum-Resistant Epithelial Ovarian Cancer (AURELIA) trial achieved its primary efficacy end point of significantly improved progression-free survival (PFS) in patients treated with bevacizumab in combination with chemotherapy (CT) compared with CT alone for platinum-resistant, recurrent ovarian cancer. Primary analyses were conducted via investigator assessment of PFS; to confirm primary results, an independent review committee (IRC) retrospectively assessed radiographic data.
The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. [2020]Bevacizumab is a biologically and clinically active antineoplastic agent in the management of epithelial ovarian cancer. While phase III trial data have revealed the favorable impact on progression-free survival associated with combining the agent with cytotoxic chemotherapy, at the current time a strong argument can be made (based on both efficacy and cost-effectiveness considerations) that a more rational approach to utilizing bevacizumab in ovarian cancer would be to administer the drug as a single agent in the platinum-resistant setting.
Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. [2023]Effective second-line treatment options for patients with recurrent ovarian clear cell carcinoma (OCCC) are limited. This case series sought to report tumor characteristics and oncologic outcomes in a small group of patients treated with combination lenvatinib and pembrolizumab. A retrospective analysis of patients with ovarian clear cell carcinoma treated with combination lenvatinib and pembrolizumab at a single institution was performed. Patient and tumor characteristics were collected including demographics and germline/somatic testing. Clinical outcomes were also evaluated and reported. Three patients with recurrent OCCC were included in the study. The median age of patients was 48 years old. All patients had platinum-resistant disease and had received 1-3 prior lines of therapy. The overall response rate was 100% (3/3). Progression-free survival ranged from 10 months to not-yet-reached. One patient remains on treatment, while the other two died of disease with overall survival of 14 and 27 months. Combination lenvatinib-pembrolizumab demonstrated favorable clinical response in these patients with platinum-resistant, recurrent, ovarian clear cell carcinoma.