REGN5668 + Cemiplimab/REGN4018 for Ovarian Cancer

Recruiting at 37 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, REGN5668 (a MUC16xCD28 costimulatory bispecific antibody), for treating ovarian and uterine cancers. Researchers aim to find the safest dose and determine its effectiveness alone or with other drugs like cemiplimab (Libtayo) or ubamatamab. Participants must have ovarian cancer previously treated with platinum-based therapy or endometrial cancer that progressed after certain treatments. This trial will assess whether these drug combinations can effectively treat these cancers. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the investigational drug ubamatamab, also known as REGN4018, has a promising safety record. In earlier studies, patients tolerated ubamatamab well, even at higher doses. While some side effects occurred, they were generally manageable and did not outweigh the potential benefits.

Cemiplimab has already received FDA approval for other uses, indicating its safety in those cases. However, its safety in this new study remains under investigation.

Specific safety data for REGN5668 is not yet available, as it is a new investigational drug. Since this study is in its early stages, the main goal is to determine a safe dosage. Researchers are closely monitoring for any side effects. Participants in these trials help researchers learn what is safe and what is not. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian cancer because they offer novel approaches compared to existing therapies like chemotherapy and targeted agents such as PARP inhibitors. REGN5668 combined with cemiplimab, or cemiplimab plus fianlimab, introduces an innovative mechanism by potentially enhancing the immune system's ability to recognize and attack cancer cells. Moreover, the combination of REGN5668 and ubamatamab could provide a new way to target and destroy cancer cells directly. These treatments aim to improve effectiveness and offer hope for better outcomes for patients with ovarian cancer.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research shows that REGN5668 is being tested to determine its ability to help the immune system attack cancer cells. Participants in this trial may receive REGN5668 with cemiplimab, or cemiplimab with fianlimab. Studies have found that cemiplimab, when combined with other treatments, can enhance the immune system's ability to fight certain types of cancer. Another arm of this trial involves REGN5668 combined with ubamatamab (REGN4018), which was tested in patients with ovarian cancer, showing a 14.3% response rate and a 57.1% disease control rate. These findings suggest that using these drugs together might help treat ovarian cancer, but further research is needed to confirm their effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Module 2 Experimental Treatment 3 Interventions

REGN5668 and ubamatamab

Group II: Module 1 Experimental Treatment 3 Interventions

REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5632

A phase 1/2 study of ubamatamab (REGN4018), a MUC16 ... Ubamatamab is a MUC16 × cluster of differentiation 3 (MUC16×CD3) bispecific antibody that bridges MUC16 on tumor cells and CD3 on T cells to promote T-cell– ...

2. esmoopen.com esmoopen.com/article/S2059-7029(23)00041-8/fulltext

41P Phase I analysis of ubamatamab (MUC16xCD3 ... Objective responses were observed between 20–800 mg. In 42 pts receiving ≥1 full dose of ≥20 mg, ORR was 14.3% (95% CI, 5.4–28.5), disease control rate was 57.1 ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02502-9/fulltext

523MO Ubamatamab (REGN4018, MUC16xCD3 bispecific ... Serum ubamatamab concentrations increased dose-proportionally. No definitive dose-response relationship was observed in safety or efficacy between 20–800 mg.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03564340

NCT03564340 | Study of REGN4018 (Ubamatamab) ... The study will also look at any signs that ubamatamab alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus; To find out ...

5. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/novel-regeneron-bispecific-antibodies-show-encouraging-anti

Novel Regeneron Bispecific Antibodies Show Encouraging ... Dose-escalation results were presented for 78 patients with recurrent ovarian cancer who had received a median of 4.5 prior treatments ...

6. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(24)00777-7/fulltext

A phase I/II study of ubamatamab (REGN4018) ... Secondary endpoints include evaluation of duration of response and progression-free survival, safety, pharmacokinetics, and change from baseline in quality of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11627180/

Translational findings support regimen selection for first‐in ... Our findings demonstrate the value of ubamatamab preclinical data to aid efficient FIH study design. Some aspects may be generalized ...