REGN4018 + Cemiplimab for Ovarian Cancer

Recruiting at 78 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: MUC16-targeted, PD-1/PD-L1

Disqualifiers: Brain tumor, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

690 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

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. ^{1 6 7 8 9}

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. ^{4 9 10 11 12}

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

Research Team

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.

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.

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
• REGN4018

Trial Overview The 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

Group I: Monotherapy Experimental Treatment 2 Interventions

REGN4018 administration

Group II: Combination Therapy Experimental Treatment 2 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)

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

In a study involving 145 patients with advanced ovarian cancer, oregovomab did not significantly improve the time to relapse (TTR) compared to placebo, with median TTRs of 13.3 months for oregovomab and 10.3 months for placebo.

However, in a specific subgroup of patients with favorable prognostic indicators (the successful front-line therapy population), oregovomab showed a promising increase in TTR to 24.0 months compared to 10.8 months for placebo, suggesting potential benefits for this subgroup that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. Berek, JS., Taylor, PT., Gordon, A., et al.[2019]

In a phase 1b/2 clinical trial involving 118 patients with recurrent platinum-sensitive epithelial ovarian cancer, the combination of ralimetinib with gemcitabine and carboplatin showed a statistically significant improvement in progression-free survival (PFS), with a median of 10.3 months compared to 7.9 months for the placebo group.

The safety profile of the ralimetinib combination therapy was generally consistent with standard chemotherapy, although there was a higher incidence of grade 3/4 elevated alanine aminotransferase in the ralimetinib group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Vergote, I., Heitz, F., Buderath, P., et al.[2022]

In a phase II study involving 59 women with recurrent, platinum-sensitive ovarian cancer, the combination of carboplatin, GM-CSF, and rIFN-gamma1b resulted in a 56% overall response rate, with 17% achieving complete response and 39% partial response.

The treatment was associated with common side effects such as bone marrow suppression and fatigue, but responders reported improved quality of life, suggesting that this regimen may be a promising option for further investigation in ovarian cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Schmeler, KM., Vadhan-Raj, S., Ramirez, PT., et al.[2021]

Platinum-resistant ovarian cancer is a challenging disease with a poor prognosis, often characterized by low immune cell infiltration, leading to low response rates (less than 8%) to anti-PD1/PD-L1 therapies.

Emerging strategies to enhance treatment efficacy include combining immune checkpoint inhibitors with chemotherapy, anti-angiogenic agents, and other immunotherapies, with ongoing studies aiming to identify optimal combinations and predictive biomarkers for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. Le Saux, O., Ray-Coquard, I., Labidi-Galy, SI.[2022]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

In a study involving 68 patients with platinum-sensitive ovarian cancer, regorafenib did not show superior efficacy compared to tamoxifen, with similar median progression-free survival of 5.6 months for tamoxifen and 4.6 months for regorafenib.

Regorafenib had a significantly worse safety profile, with 90.9% of patients experiencing grade 3/4 adverse events, compared to 54.3% for tamoxifen, highlighting concerns about its tolerability in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Trédan, O., Provansal, M., Abdeddaim, C., et al.[2022]

Ruxolitinib, a JAK1/JAK2 inhibitor, effectively inhibits STAT3 activation and reduces ovarian tumor growth in both cancer cells and mouse models, suggesting its potential as a treatment for ovarian cancer.

When combined with the chemotherapy agent paclitaxel, ruxolitinib significantly enhances anti-tumor activity, leading to greater tumor reduction compared to using either treatment alone, indicating a promising strategy for advanced and chemoresistant ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer. Han, ES., Wen, W., Dellinger, TH., et al.[2021]

In high grade serous ovarian cancer (HGSOC), the immune receptors TIM-3 and OX40 are highly expressed, suggesting they could be targeted to improve responses to immunotherapy, especially since PD-1 levels are lower in these tumors.

OX40 expression is significantly associated with improved patient survival, indicating it may serve as a valuable prognostic factor for better outcomes in HGSOC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. James, NE., Valenzuela, AD., Emerson, JB., et al.[2022]

Recombinant human CD40L (rhuCD40L) effectively inhibits the growth of ovarian adenocarcinomas in a mouse model, showing that two treatment cycles are more effective than one, and this effect is not dependent on natural killer cells.

rhuCD40L enhances the effectiveness of cisplatin chemotherapy, allowing lower doses of cisplatin to achieve similar antitumor effects as higher doses, suggesting its potential as a combination therapy for treating epithelial ovarian tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ghamande, S., Hylander, BL., Oflazoglu, E., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

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]

4. United States pubmed.ncbi.nlm.nih.gov

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]

5. England pubmed.ncbi.nlm.nih.gov

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

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]

10. United States pubmed.ncbi.nlm.nih.gov

Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer. [2021]

11. Greece pubmed.ncbi.nlm.nih.gov

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]

12. United States pubmed.ncbi.nlm.nih.gov

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]