REGN5668 + Cemiplimab/REGN4018 for Ovarian Cancer

Recruiting at 36 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Recent cancer, Autoimmune, Brain tumor, others

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

Compensation: Varies

Number of Visits: Unknown

612 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is researching an investigational drug called REGN5668. Participants will receive additional investigational drugs in combination with REGN5668. These additional drugs include cemiplimab or REGN4018 (with or without sarilumab). The main purposes of this study are to: * Learn about the safety and profile of any side effects from the study drugs and to determine the highest, safe dose that can be given to participants with ovarian cancer or cancer of the uterus * Look for signs that the study drugs can treat ovarian cancer or cancer of the uterus This study has 2 parts. The purpose of Part 1 (Escalation) to find the highest, safe dose of the study drug(s). The purpose of Part 2 (Expansion) is to use the doses chosen in Part 1. Participants with cancer of the uterus will only participate in Part 2. The study is looking at several other research questions, including: * Side effects that may be experienced by participants taking REGN5668 alone and/or in combination with cemiplimab or REGN4018 * How REGN5668 works in the body either alone and/or in combination with cemiplimab or REGN4018 * How much of the study drugs (REGN5668, cemiplimab, REGN4018) are in the blood * To see if REGN5668 in combination with cemiplimab or REGN4018 works to treat cancer * To find out how safe, tolerable, and effective in mitigating Cytokine Release Syndrome (CRS) sarilumab pretreatment is when given before REGN4018

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, if you are on continuous corticosteroid therapy, you may need to stop it at least one week before starting the study drugs.

What data supports the effectiveness of the drug REGN5668 + Cemiplimab/REGN4018 for ovarian cancer?

The bispecific antibody REGN4018, which is part of the treatment, has shown promising results in preclinical studies by activating immune cells to target ovarian cancer cells, leading to tumor growth inhibition. Additionally, combining REGN4018 with an anti-PD-1 antibody, similar to Cemiplimab, enhanced its effectiveness in these studies. ^{1 2 3 4 5}

What makes the drug REGN5668 + Cemiplimab/REGN4018 unique for ovarian cancer?

This drug is unique because it uses bispecific antibodies, like REGN4018, to target MUC16, a protein highly expressed on ovarian cancer cells, and CD3 on T cells, effectively bridging and activating the immune system to attack the cancer cells. This approach is innovative compared to traditional chemotherapy, offering a new immunotherapy strategy for treating ovarian cancer. ^{1 3 6 7 8}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for adult women with advanced ovarian, fallopian tube, or peritoneal cancer who've had at least one platinum-based therapy. They should have a life expectancy of over 3 months, good organ and bone marrow function, and higher than normal CA-125 levels. Exclusions include ongoing steroid use, recent anti-cancer immunotherapy or MUC16-targeted therapy, more than three prior chemo treatments for certain conditions (expansion phase), significant autoimmune disease requiring treatment within the last 5 years, active brain tumors/CNS metastases/spinal cord compression, or serious heart disease.

Inclusion Criteria

My organs and bone marrow are functioning well.

I am fully active or restricted in physically strenuous activity but can do light work.

You are expected to live for at least 3 more months.

Exclusion Criteria

I have had another cancer in the last 5 years that is getting worse or might come back.

I have an untreated brain tumor or cancer that has spread to my brain or spinal cord.

I am on continuous corticosteroid therapy as per my treatment plan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

The purpose of Part 1 (Escalation) is to find the highest, safe dose of the study drug(s).

6 weeks

Multiple visits for dose escalation and monitoring

Dose Expansion

The purpose of Part 2 (Expansion) is to use the doses chosen in Part 1.

Up to 5 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cemiplimab
• REGN4018
• REGN5668

Trial Overview The study tests REGN5668 alone and in combination with either cemiplimab or REGN4018 to find safe dosages (Dose Escalation Phase) and to evaluate preliminary effectiveness based on tumor response rates (Dose Expansion Phase). It also examines safety profiles, pharmacokinetics (how the body processes the drugs), changes in CA-125 levels after treatment with these combinations.

Participant Groups

Group I: Module 2 Experimental Treatment 3 Interventions

REGN5668 and REGN4018

Group II: Module 1 Experimental Treatment 2 Interventions

REGN5668 and cemiplimab

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

The standard treatment for platinum-resistant ovarian cancer involves non-platinum chemotherapy, with weekly paclitaxel showing the greatest benefits, but overall response rates remain modest, highlighting the need for improved therapies.

Recent trials indicate that while combination treatments with antiangiogenics have improved outcomes, there is still a lack of reliable biomarkers to predict treatment response, emphasizing the importance of thoughtful clinical trial designs and the exploration of novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. Eskander, RN., Moore, KN., Monk, BJ., et al.[2023]

The combination of Atezolizumab (an anti-PD-L1 therapy) and Bevacizumab (a chemotherapy adjunct) significantly enhances anti-tumor effects in cisplatin-resistant epithelial ovarian cancer, as shown by improved cell proliferation, migration, and invasion inhibition in vitro and synergistic effects in vivo.

In a study of 124 patients, higher expressions of PD-L1, VEGF, and Semaphorin4D were associated with better responses to Bevacizumab-containing chemotherapy, indicating that these markers could help predict treatment outcomes and guide future therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition. Zhang, L., Chen, Y., Li, F., et al.[2020]

REGN4018, a bispecific antibody targeting MUC16 on ovarian cancer cells and CD3 on T cells, effectively activates T cells to kill tumor cells in vitro and shows potent antitumor activity in preclinical models, including immunocompetent mice.

Toxicology studies in cynomolgus monkeys indicated that REGN4018 has good tolerability, with only minimal and transient increases in serum cytokines and no significant toxicity, supporting its potential for clinical evaluation in patients with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Mucin 16 bispecific T cell-engaging antibody for the treatment of ovarian cancer. Crawford, A., Haber, L., Kelly, MP., et al.[2020]

Targeted therapies for platinum-resistant ovarian cancer, such as bevacizumab and olaparib, have shown promising results in clinical trials, offering new hope for patients with this challenging disease.

Identifying response predictive biomarkers is crucial for tailoring treatments to specific patient populations, which can improve clinical outcomes and reduce unnecessary side effects from ineffective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection and targeted treatment in the management of platinum-resistant ovarian cancer. Leamon, CP., Lovejoy, CD., Nguyen, B.[2021]

In a phase III study involving 888 patients with ovarian cancer in first clinical remission, abagovomab maintenance therapy was found to be safe and induced a measurable immune response, with common side effects including injection site reactions and fatigue.

However, the study concluded that abagovomab did not significantly prolong recurrence-free survival (RFS) or overall survival (OS) compared to placebo, indicating that it may not be an effective maintenance therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO--the MIMOSA study. Sabbatini, P., Harter, P., Scambia, G., et al.[2021]

Bivalent low-affinity bispecific antibodies targeting the LYPD1 antigen in high-grade serous ovarian cancers (HGSOC) effectively activate T cells and inhibit tumor growth, showing promising anti-tumor activity.

The bivalent TCB (QZC131) demonstrated selectivity for high LYPD1-expressing tumor cells and was well-tolerated in cynomolgus monkeys at doses up to 3 mg/kg, indicating a favorable safety profile for potential clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer. Lee, E., Szvetecz, S., Polli, R., et al.[2023]

A bispecific antibody (bsAb) targeting TRAIL-R2 and CD3 effectively activates T cells and redirects their cytotoxicity against various cancer cells in vitro, suggesting its potential as a broad treatment for different types of cancer.

In an ex vivo model using ovarian cancer patients' ascitic fluids, the bsAb demonstrated significant retargeting of T-cell activity, even with a less-than-ideal ratio of effector to target cells, indicating its practical applicability in real patient scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy. Satta, A., Grazia, G., Caroli, F., et al.[2020]

In a murine model of advanced ovarian cancer, carboplatin treatment alone significantly improved overall survival compared to the combination of carboplatin and anti-PD-L1 monoclonal antibody, indicating that carboplatin may be more effective as a standalone treatment in this context.

Both carboplatin and the combination treatment increased the presence of antitumor CD4+ and CD8+ T cells while reducing immunosuppressive cells, suggesting that carboplatin enhances the immune response against tumors, which could inform future cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model. Zhu, X., Xu, J., Cai, H., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition. [2020]

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

A Mucin 16 bispecific T cell-engaging antibody for the treatment of ovarian cancer. [2020]

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

Patient selection and targeted treatment in the management of platinum-resistant ovarian cancer. [2021]

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

Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO--the MIMOSA study. [2021]

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

PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy. [2020]

8. Australia pubmed.ncbi.nlm.nih.gov

Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model. [2018]