REGN4018 + Cemiplimab for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
+77 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Regeneron Pharmaceuticals
Must not be taking: MUC16-targeted, PD-1/PD-L1
Disqualifiers: Brain tumor, Cardiovascular disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
The main purpose of this study is to: * Learn about the safety of REGN4018 and to find out what dose of REGN4018 can be given alone or with cemiplimab to patients with ovarian cancer or cancer of the uterus * The study will also look at the levels of REGN4018 and/or cemiplimab in your body and measure how well your body can remove the study drug(s). This is called pharmacokinetics * The study will also look at any signs that REGN4018 alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus * To find out how safe and tolerable the sarilumab pretreatment is, in combination with REGN4018 and cemiplimab
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 anti-hypertensive medication, you must be on a stable regimen.
What data supports the effectiveness of the drug REGN4018 + Cemiplimab for ovarian cancer?
The research indicates that ovarian cancer is often resistant to treatments, but there are ongoing efforts to improve response rates by combining different therapies, including immune checkpoint inhibitors like Cemiplimab. Although direct evidence for REGN4018 + Cemiplimab is not provided, similar strategies are being explored to enhance the effectiveness of immunotherapy in ovarian cancer.12345
What safety data exists for Cemiplimab (Libtayo) in humans?
Cemiplimab (Libtayo) has been approved for use in certain types of skin and lung cancers, with common side effects including fatigue, rash, and diarrhea. It works by helping the immune system attack cancer cells, but it can also cause the immune system to attack normal organs and tissues, which may lead to serious side effects.16789
How is the drug REGN4018 + Cemiplimab different from other ovarian cancer treatments?
REGN4018 + Cemiplimab is unique because it combines an immune checkpoint inhibitor (cemiplimab) with a bispecific antibody (REGN4018) that targets ovarian cancer cells, potentially enhancing the immune system's ability to fight the cancer. This approach is different from traditional chemotherapy, which directly targets cancer cells, and may offer a new option for patients with ovarian cancer.49101112
Research Team
CT
Clinical Trial Management
Principal Investigator
Regeneron Pharmaceuticals
Eligibility Criteria
This trial is for adults with recurrent ovarian, fallopian tube, or peritoneal cancer who've had platinum-based therapy or are intolerant to it. They should have no standard treatment options left and a life expectancy of at least 3 months. Those with specific heart conditions, recent anti-PD-1/PD-L1 therapy, MUC16-targeted therapy history, untreated brain tumors or CNS metastases aren't eligible.Inclusion Criteria
My organs and bone marrow are working well.
I have been diagnosed with advanced ovarian, peritoneal, or fallopian tube cancer.
I have no standard treatment options left.
See 5 more
Exclusion Criteria
I have a history of heart issues as described in the study details.
My high blood pressure is under control with stable medication.
I have been treated with a therapy targeting MUC16 before.
See 3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants receive escalating doses of REGN4018 alone or with cemiplimab to determine safety and optimal dosing
Up to 62 weeks
Dose Expansion
Participants receive the determined dose of REGN4018 alone or with cemiplimab to further evaluate safety and efficacy
Up to 62 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4-8 weeks
Treatment Details
Interventions
- Cemiplimab (Monoclonal Antibodies)
- REGN4018 (Monoclonal Antibodies)
Trial OverviewThe study tests REGN4018 alone and combined with cemiplimab in two phases: Dose Escalation to find the safest dose and Dose Expansion to evaluate effectiveness by tumor response rates. It also examines side effects profiles, drug levels in the body (pharmacokinetics), and impacts on quality of life.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: MonotherapyExperimental Treatment2 Interventions
REGN4018 administration
Group II: Combination TherapyExperimental Treatment2 Interventions
REGN4018 and cemiplimab administration
Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:
🇪🇺 Approved in European Union as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Non-small cell lung cancer (NSCLC)
🇺🇸 Approved in United States as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Basal cell carcinoma (BCC)
- Non-small cell lung cancer (NSCLC)
🇨🇦 Approved in Canada as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
- Non-small cell lung cancer (NSCLC)
🇧🇷 Approved in Brazil as Libtayo for:
- Cutaneous squamous cell carcinoma (CSCC)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Regeneron Study SiteNew York, NY
Virginia Commonwealth University Medical CenterRichmond, VA
The General Hospital Corporation d/b/a Massachusetts General HospitalBoston, MA
Regeneron Study SiteHilliard, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Regeneron Pharmaceuticals
Lead Sponsor
Trials
690
Patients Recruited
948,000+
Founded
1988
Headquarters
Tarrytown, USA
Known For
Precision medicine
Top Products
Dupixent, EYLEA, Libtayo, Praluent
References
Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. [2023]To explore whether patients with BRCA1/2-mutated or homologous recombination deficient (HRD) ovarian cancers benefitted from atezolizumab in the phase III IMagyn050 (NCT03038100) trial.
Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. [2019]To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study.
A randomized, double-blind, placebo-controlled phase 1b/2 study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine and carboplatin versus gemcitabine and carboplatin for women with recurrent platinum-sensitive ovarian cancer. [2022]This phase 1b/2 clinical trial (NCT01663857) evaluated the efficacy of ralimetinib in combination with gemcitabine (G) and carboplatin (C), followed by maintenance ralimetinib, for patients with recurrent platinum-sensitive epithelial ovarian cancer.
A phase II study of GM-CSF and rIFN-gamma1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. [2021]To evaluate the efficacy and toxicity of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-gamma1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer.
Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. [2022]Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8+ T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.). Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated. Each approach faces distinct challenges that will be reviewed here. Robust immunogenomics studies conducted in parallel of the ongoing trials will help into refining optimal immunotherapy combination for this lethal disease and identify predictive biomarkers.
Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]Introduction: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. Areas Covered: We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. Expert Opinion: Immunotherapy, specifically checkpoint inhibitors, represents an increasingly utilized class of medications that is proving to be an effective treatment option for those with certain cancers. Over time, immunotherapy is likely to be the standard of care for immune-sensitive tumors. There are many challenges that the field faces, including the identification of reliable biomarkers to better predict response, decreasing toxicity, and the potential treatment of organ transplant patients.
Cemiplimab: First Global Approval. [2023]Cemiplimab (LIBTAYO®; cemiplimab-rwlc), a human programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and blocks its interaction with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Regeneron Pharmaceuticals and Sanofi Genzyme. The drug is being investigated as a treatment for various cancers and in September 2018 received approval in the USA for the treatment of patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation. This article summarizes the milestones in the development of cemiplimab leading to this first global approval for the treatment of advanced cutaneous squamous cell carcinoma.
Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. [2023]In metastatic non-small cell lung cancer (NSCLC), tumors that do not harbor driver mutations in EGFR or gene fusions in ALK and ROS, PD-1 and PD-L1 inhibitors have become a cornerstone in first line treatment, either as monotherapy or in combination with chemotherapy. This paper reviews cemiplimab-rwlc, the third PD-1/L1 inhibitor to be approved in the setting for first line treatment in NSCLC, as monotherapy or in combination therapy with chemotherapy, to provide a perspective on the subtle differences in patient population for the cemiplimab studies and consideration of its primary and subgroup results in the context of first line therapies for NSCLC.
Regorafenib or Tamoxifen for platinum-sensitive recurrent ovarian cancer with rising CA125 and no evidence of clinical or RECIST progression: A GINECO randomized phase II trial (REGOVAR). [2022]To evaluate the efficacy and safety of regorafenib versus tamoxifen in platinum-sensitive ovarian cancer biological recurrence, defined by CA-125 increase without radiological (RECIST criteria) or symptomatic evidence of progression.
Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer. [2021]Treatment for ovarian cancer remains challenging despite a high initial response rate to first line platinum-taxane treatment. Most patients eventually experience recurrence and require further treatment. Persistent activation of STAT3 is associated with cancer growth and progression and is also involved in cell resistance to platinum and taxane treatment. Targeting JAK/STAT3, therefore, could be a potential novel therapeutic approach for treating advanced and chemoresistant ovarian cancer. We investigated the therapeutic potential of ruxolitinib, a JAK1/JAK2 inhibitor that has been FDA-approved for the treatment of myelofibrosis, to treat ovarian cancer either alone or in combination with conventional chemotherapy agents. We show that ruxolitinib inhibits STAT3 activation and ovarian tumor growth both in ovarian cancer cells and in an ovarian cancer mouse model. In addition, ruxolitinib significantly increases the anti-tumor activity of chemotherapy agents, including paclitaxel, cisplatin, carboplatin, doxorubicin and topotecan in ovarian cancer cells. Evaluation of the combination index (CI) shows that ruxolitinib synergistically interacts with paclitaxel in all three human ovarian cancer cells. Finally, our results demonstrate that combination of ruxolitinib and paclitaxel leads to a greater reduction of tumor growth compared to single treatment of either agent in a tumor mouse model that represents late stage ovarian cancer with peritoneal metastasis and ascites formation. Taken together, our findings provide a foundation for clinical trials with ruxolitinib, either as a single agent or in combination with paclitaxel, for the treatment of recurrent and advanced ovarian cancer.
Intratumoral expression analysis reveals that OX40 and TIM-3 are prominently expressed and have variable associations with clinical outcomes in high grade serous ovarian cancer. [2022]Patients with ovarian cancer exhibit low response rates to anti-programmed cell death protein-1 (PD-1) based therapies, despite ovarian tumors demonstrating measurable immune responses. Therefore, the aim of the present study was to comparatively examine expression of notable immune co-stimulatory and co-inhibitory receptors in order identify the most abundant receptors that could potentially serve as therapeutic targets to enhance immunotherapy response in high grade serous ovarian cancer (HGSOC). The Cancer Genome Atlas (TCGA) was employed to compare levels of various HGSOC and pan-cancer cohorts. To confirm these findings at the protein level, immunofluorescence of select receptors was performed in 29 HGSOC patient tissue samples. TCGA and Kaplan Meier analysis was employed to determine the association of highly expressed immune receptors with clinical outcomes. TIM-3 and OX40 exhibited the highest expression in HGSOC at both the gene and protein level, with TIM-3 demonstrating highest levels on both CD8+ and CD4+ T cell subsets. Pan-cancer analysis determined that TIM-3 and OX40 levels were similar to those in immunotherapy-responsive cancers, while PD-1 exhibited much lower expression in HGSOC. Finally, OX40 was most strongly associated with improved patient survival. Overall, the current study suggested that TIM-3 and OX40 are frequently expressed intratumoral immune receptors in HGSOC and thus represent promising immune targets. Furthermore, the present analysis strongly suggested that OX40 was significantly associated with a longer survival and could potentially be utilized as a prognostic factor for improved patient outcomes in HGSOC.
Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. [2013]CD40 is a member of the tumor necrosis factor receptor family and was first identified with a monoclonal antibody raised against bladder carcinoma. Recombinant human CD40L has been shown previously to have a direct antitumor effect on an ovarian cancer cell line and ovarian carcinoma cells isolated from ascites fluid. We show here that rhuCD40L inhibits the growth of several ovarian adenocarcinomas derived from surgical specimens and grown as xenografts in severe combined immunodeficient mice. Two 14-day treatment cycles were more effective than one. This effect is apparently not mediated by natural killer cells, because blocking natural killer cell activity by antiasialo GM-1 did not diminish this effect. In addition to suppression of tumor growth, treatment with rhuCD40L resulted in an increased expression of FasL, an increase in apoptosis, and histological changes including increased fibrosis and areas of tumor destruction. Using this model, we examined the efficacy of rhuCD40L in combination with chemotherapeutic agents. The antitumor effect of rhuCD40L in combination with 4 mg/kg cisplatin (CDDP) was increased over the effect of CDDP alone. Furthermore, rhuCD40L increased the efficacy of a suboptimal dose of CDDP (2mg/kg) such that it matched that of high-dose CDDP alone. These data suggest a role for rhuCD40L therapy in combination with platinum based regimens for primary treatment of epithelial ovarian tumors.