27T51 Therapy for Ovarian Cancer

Recruiting at 3 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Immunosuppressants, Gene therapy

Disqualifiers: Inadequate organ function, CNS pathology, others

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

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 27T51 for women with hard-to-treat ovarian, primary peritoneal, or fallopian tube cancer. Researchers aim to determine if this treatment, which uses modified immune cells (Anti-MUC16 CAR T-cells), is safe and effective. The trial consists of two parts: the first part identifies a safe dose, and the second part tests this dose alone or with other medicines. Women with recurring or resistant ovarian cancer and noticeable tumors might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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 treatments for autoimmune diseases or have had cellular or gene therapy, you may not be eligible to participate.

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

Research has shown that 27T51 is a new type of treatment called CAR T cell therapy, targeting a protein often found in ovarian cancer. This treatment is being tested for safety. Like other CAR T cell therapies, 27T51 might cause immune system-related side effects, such as cytokine-associated toxicities. Another possible side effect is 'on-target, off-tumor' toxicity, where healthy cells might also be affected. Researchers closely monitor these reactions during the trial.

The trial also examines how 27T51 works when combined with other drugs, cemiplimab and bevacizumab. Cemiplimab is already used in some cancer treatments, so its safety is well-known. Bevacizumab is FDA-approved for other uses, indicating it is considered safe within certain limits.

As this is an early-phase trial, the main goal is to find the highest dose that remains safe. Researchers carefully monitor any side effects to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the 27T51 therapy for ovarian cancer because it offers a fresh approach compared to traditional treatments like surgery, chemotherapy, and targeted therapies. The 27T51 monotherapy is unique due to its novel mechanism of action, potentially offering benefits as a standalone treatment. Additionally, when combined with Cemiplimab, an immune checkpoint inhibitor, and Bevacizumab, an anti-angiogenic drug, it could enhance the immune system's ability to fight cancer and inhibit blood vessel growth that tumors need to thrive. This combination strategy might improve outcomes where standard treatments may not be as effective.

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

Studies have shown that 27T51, a type of CAR T cell therapy, targets a protein called MUC16, often found on ovarian cancer cells. Early research demonstrated that this treatment effectively shrinks tumors. In this trial, some participants will receive 27T51 monotherapy, while others will receive 27T51 combined with Cemiplimab, a drug that helps the immune system fight cancer, to potentially enhance its effects. Additionally, another group will receive 27T51 combined with both Cemiplimab and Bevacizumab, which prevents tumors from growing new blood vessels, to assess if this combination might increase the treatment's effectiveness. Researchers are studying these combination therapies to determine if they can offer better results for patients with difficult-to-treat ovarian cancer. ^{1 4 5 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 recurrent or hard-to-treat ovarian, primary peritoneal, or fallopian tube cancer. Participants should have tried other treatments that didn't work well. The study will exclude certain individuals based on specific medical criteria not listed here.

Inclusion Criteria

Participants must have at least 1 measurable tumor lesion as defined by the response evaluation criteria in solid tumors (RECIST) 1.1

Expected survival ≥ 3 months

My cancer is ovarian, peritoneal, or fallopian tube and has come back or didn't respond to treatment.

Exclusion Criteria

Absolute lymphocyte count (ALC) < 100 cells/μL at time of leukapheresis

I haven't had serious bleeding or blood clotting issues in the last month.

I have a known brain condition that is significant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Dose Escalation

Test the safety of 27T51 in a small number of participants to find the highest dose without unacceptable side effects

Up to 18 months

Phase 1b Dose Expansion

Test 27T51 at the established dose level(s) and may include other medications given in combination

Up to 48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 27T51

Trial Overview The trial is testing a new CAR T cell therapy called 27T51 alone and in combination with Cemiplimab and Bevacizumab. It has two parts: finding the highest safe dose (Phase 1a) and then using this dose to further evaluate safety and effectiveness (Phase 1b).

How Is the Trial Designed?

Group I: Dose Expansion - Arm C Experimental Treatment 3 Interventions

27T51+Cemiplimab+Bevacizumab

Group II: Dose Expansion - Arm B Experimental Treatment 2 Interventions

27T51+Cemiplimab

Group III: Dose Expansion - Arm A Experimental Treatment 1 Intervention

27T51 monotherapy

Group IV: Dose Escalation Experimental Treatment 1 Intervention

27T51 monotherapy

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

The study developed a fourth-generation CAR T cell therapy targeting the MUC1 antigen, which is highly expressed in cholangiocarcinoma (CCA) and linked to poor patient outcomes, showing promise as a new treatment option.

Anti-MUC1-CAR4 T cells demonstrated significant cytotoxic activity against CCA cell lines, achieving up to 66% cell killing, while sparing normal cholangiocytes, indicating a targeted and potentially safer therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-mucin 1 chimeric antigen receptor T cells for adoptive T cell therapy of cholangiocarcinoma. Supimon, K., Sangsuwannukul, T., Sujjitjoon, J., et al.[2021]

Chimeric antigen receptor-modified T (CAR-T) cell therapy shows promising clinical efficacy in treating ovarian cancer, as supported by various preclinical experiments and clinical trials.

While CAR-T therapy offers a novel approach to cancer treatment, it is associated with side effects and toxicities, including cytokine release syndrome and 'on-target, off-tumor' effects, which need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cell therapy in ovarian cancer: from the bench to the bedside. Zhu, X., Cai, H., Zhao, L., et al.[2019]

The study developed a novel CAR T cell therapy targeting the MUC-16ecto antigen in ovarian cancer, showing that the addition of IL-12 enhances T cell proliferation and IFNγ secretion, leading to improved antitumor efficacy in mouse models.

To ensure safety in potential clinical applications, the CAR T cells include an elimination gene that allows for their removal in case of unexpected side effects, making this approach both innovative and cautious.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. Koneru, M., Purdon, TJ., Spriggs, D., et al.[2021]

Engineered CAR T cells targeting both Muc16 and WT1 antigens in ovarian cancer show enhanced anticancer activity, especially against tumors with low Muc16 expression, indicating a promising approach to improve treatment efficacy.

The use of a bispecific T cell engager (BiTE) allows these CAR T cells to recruit additional T cells to attack cancer cells, demonstrating a novel strategy to overcome the limitations of traditional CAR T cell therapies in heterogeneous tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual targeting ovarian cancer by Muc16 CAR-T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1. Mun, SS., Peraro, L., Meyerberg, J., et al.[2023]

A new preclinical mouse model for MUC1-positive ovarian tumors was developed, which closely mimics human ovarian cancer, showing increased metastasis and immune suppression, making it a valuable tool for testing therapies.

Vaccination with dendritic cells loaded with a MUC1 peptide effectively activates the immune response and prolongs survival in these mice, highlighting MUC1 as a promising target for immune-based treatments in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunobiology of human mucin 1 in a preclinical ovarian tumor model. Budiu, RA., Elishaev, E., Brozick, J., et al.[2021]

Engineered CAR T cells targeting both Muc16 and WT1 antigens in ovarian cancer show enhanced anticancer activity, especially against tumors with low Muc16 expression, indicating a promising approach to overcome treatment resistance.

The use of a bispecific T cell engager (BiTE) allows these CAR T cells to recruit additional T cells to attack cancer cells, enhancing the overall effectiveness of the therapy in both laboratory and mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual targeting ovarian cancer by Muc16 CAR T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1. Mun, SS., Meyerberg, J., Peraro, L., et al.[2023]

Citations

1. physicianresources.roswellpark.org physicianresources.roswellpark.org/news/clinical-trial-offers-car-t-cell-therapy-targeting-muc16-for-recurrent/refractory-ovarian-cancer

Clinical Trial Offers CAR T-Cell Therapy Targeting MUC16 ... This trial is designed to evaluate an experimental CAR T-cell therapy targeting MUC16, a well-established ovarian cancer antigen.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06080

A Study to Learn if 27T51, a Mucin-16 (MUC16) Protein ... The study drug is a MUC16 targeting immune cell therapy focused on adult female participants with recurrent or difficult to treat epithelial ovarian, primary ...

3. withpower.com withpower.com/trial/phase-1-carcinoma-ovarian-epithelial-5-2024-ed43a

27T51 Therapy for Ovarian Cancer Engineered CAR T cells targeting both Muc16 and WT1 antigens in ovarian cancer show enhanced anticancer activity, especially against tumors with low Muc16 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11573523/

Emerging strategies to overcome ovarian cancer: advances in ... In this study, a partial response was observed in two patients (8.7%), one with OC and one with uterine cancer, with a response duration of 14.8 ...

5. sigma.larvol.com sigma.larvol.com/moa.php?MoaId=874605&tab=newstrac

MUC16-targeted CAR-T immunotherapy News Our findings demonstrate that CA125 targeting CR and CAR can synergistically kill ovarian cancer cells, indicating that CA125 targeting by the two binding ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-muc16-car-t-cells-27t51?pn=1

Clinical Trials Using Anti-MUC16 CAR T-cells 27T51 - NCI Review the clinical trials studying anti-muc16 car t-cells 27t51 on this list and use the filters to refine the results by age and location.

7. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy00000019MHEAY/nct06469281

A Study to Learn if 27T51, a Mucin-16 (MUC16) Protein ... This study is researching an experimental CAR T cell therapy called 27T51, referred to as study drug. The study drug is a MUC16 targeting immune cell therapy ...