REGN4336 + Cemiplimab for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+17 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Regeneron Pharmaceuticals
Must be taking: Androgen deprivation therapy
Must not be taking: Corticosteroids, Biologics, Immunosuppressives, others
Disqualifiers: Autoimmune disease, Neurodegenerative disease, Infections, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This trial is testing a new cancer drug called REGN4336, alone or with other drugs, to see if it is safe and effective. It aims to help the immune system attack cancer cells. The study focuses on finding the right dose and understanding side effects.
Will I have to stop taking my current medications?
The trial requires that you stop taking any approved systemic therapy at least 3 weeks before starting the study drugs. If you're on corticosteroids, you need to be on a low dose (10 mg prednisone/day or less) at least 1 week before starting the trial.
What data supports the effectiveness of the drug REGN4336 + Cemiplimab for prostate cancer?
The research highlights that bispecific antibodies like the PSMAxCD3 antibody can target prostate-specific membrane antigens on cancer cells, potentially offering a dual anticancer effect. However, while bispecific antibodies are promising in theory, they have not yet been successful in treating solid tumors like prostate cancer.12345
What makes the drug REGN4336 + Cemiplimab unique for prostate cancer?
REGN4336 + Cemiplimab is unique because it combines a bispecific antibody that targets prostate-specific membrane antigen (PSMA) on cancer cells with an immune checkpoint inhibitor, potentially enhancing the immune system's ability to attack prostate cancer cells. This approach is novel as it leverages both targeted and immune-based strategies, which are not yet standard for prostate cancer treatment.12567
Eligibility Criteria
Adults with advanced prostate cancer that's resistant to castration and has worsened despite treatment, including at least one second-generation anti-androgen therapy. Participants must have a PSA level of ≥4 ng/mL and cannot be on high-dose steroids or have had certain recent treatments like systemic biologics, PSMA-targeting therapies, or suffer from significant autoimmune diseases.Inclusion Criteria
My prostate cancer has spread, is resistant to hormone therapy, and my PSA is 4 or higher.
My prostate cancer is confirmed but not as a pure small cell type.
My cancer has worsened after 2 or more treatments, including a modern anti-androgen therapy.
Exclusion Criteria
I have an autoimmune disease treated with immune-weakening drugs in the last 5 years.
I haven't taken high doses of steroids or similar medicines in the last week.
I haven't taken any immune therapy (except Sipuleucel-T) recently.
See 4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Determine a safe dose of REGN4336 when given alone or in combination with cemiplimab or REGN5678
28 to 42 days
Dose Expansion
Test how well REGN4336 works to shrink tumors either alone or in combination with cemiplimab or REGN5678
Up to 5 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Cemiplimab (Monoclonal Antibodies)
- REGN4336 (Monoclonal Antibodies)
Trial OverviewThe trial is testing REGN4336 alone and combined with Cemiplimab to evaluate safety, tolerability, dosage levels (Dose Escalation), and preliminary effectiveness in reducing tumor size (Dose Expansion) based on objective response rate criteria. It also examines the drugs' pharmacokinetics—their movement through the body.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Module 3-Combo TherapyExperimental Treatment3 Interventions
REGN4336 + REGN5678
Group II: Module 2-Combo TherapyExperimental Treatment3 Interventions
REGN4336 + Cemiplimab
Group III: Module 1- MonotherapyExperimental Treatment2 Interventions
REGN4336
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:
University of Pennsylvania Perelman Center for Advanced MedicinePhiladelphia, PA
Froedtert and Medical College of WisconsinMilwaukee, WI
Regeneron Study SitePhiladelphia, PA
Stanford University Medical Center - Blake Wilbur DrivePalo Alto, CA
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Regeneron PharmaceuticalsLead Sponsor
References
Protocol of a prospective, multicentre phase I study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration-resistant prostate carcinoma. [2021]Prostate cancer is the second most common cancer in men worldwide. When the disease becomes resistant to androgen-deprivation therapy, treatment options are sparse. To address the high medical need in castration-resistant prostate cancer (CRPC), we generated a novel PSMAxCD3 bispecific antibody termed CC-1. CC-1 binds to prostate-specific membrane antigen that is expressed on prostate cancer cells and tumour vessels, thereby allowing a dual anticancer effect.
Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives. [2021]Prostate carcinoma (PC) is the second most common cancer in men. When the disease becomes unresponsive to androgen deprivation therapy, the remaining treatment options are of limited benefit. Despite intense efforts, none of the T cell-based immunotherapeutic strategies that meanwhile have become a cornerstone for treatment of other malignancies is established in PC. This refers to immune checkpoint inhibition (CI), which generally reinforces T cell immunity as well as chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) that stimulate the T cell receptor/CD3-complex and mobilize T cells in a targeted manner. In general, compared to CAR-T cells, bsAb would have the advantage of being an "off the shelf" reagent associated with less preparative effort, but at present, despite enormous efforts, neither CAR-T cells nor bsAbs are successful in solid tumors. Here, we focus on the various bispecific constructs that are presently in development for treatment of PC, and discuss underlying concepts and the state of clinical evaluation as well as future perspectives.
Targeted therapies for prostate cancer. [2019]The development of targeted therapies for prostate cancer has exploited various elements of prostate biology. The androgen-dependence of prostate cancer continues to be the focus for the development of new drugs and the analysis of details of the intermolecular interactions of the androgen receptor. Importantly, new applications of androgen ablation therapy have proven to have the greatest effect on cause-specific and overall survival during the last decade. Prostate epithelial cells express a number of tissue-specific proteins that have been the target either for antibody-directed therapies, in the case of prostate-specific membrane antigen, or target-activated therapies in the case of prostate-specific antigen, a serine protease. Prostate-specific proteins have also been targeted by the development of vaccines that have entered clinical trials. Humanized monoclonal antibodies and small molecules designed to inhibit oncogenic signalling pathways have been subjected to clinical trials in prostate cancer with limited success. The application of pathway inhibitors to prostate cancer therapy has been limited because no common dominant oncogenic mutation affecting signal kinase activation in prostate cancer has yet been identified. The interaction of signal kinase inhibitors with androgen ablation and with cytotoxic chemotherapy remains to be explored.
Novel agents in the management of castration resistant prostate cancer. [2022]Prostate cancer (PCa) is a leading cause of cancer mortality in men and despite high cure rates with surgery and/or radiation, 30-40% of patients will eventually develop advanced disease. Androgen deprivation is the first line therapy for standard of care for men with advanced disease. Eventually however all men will progress to castration-resistant prostate cancer (CRPC). Insight into the molecular mechanisms of androgen resistance has led to the development of alternative novel hormonal agents. Newer hormonal agents such as abiraterone, enzalutamide and TOK-001; and the first cancer vaccine, Sipuleucel T have been approved for use in men with CRPC. The recognition of the importance of bone health and morbidity associated with skeletal related events has led to the introduction of the receptor activator of nuclear factor kappa-B-ligand inhibitor denosumab. Other molecularly targeted therapies have shown promise in pre-clinical studies, but this has not consistently translated into clinical efficacy. It is increasingly evident that CRPC is a heterogeneous disease and an individualized approach directed at identifying primary involvement of specific pathways could maximize the benefit from targeted therapies. This review focuses on targeted therapy for PCa with special emphasis on therapies that have been Food and Drug Administration approved for use in men with CRPC.
A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer. [2016]This phase II open-label study evaluated the effect of concurrent or sequential administration of abiraterone acetate plus prednisone (AA + P) on sipuleucel-T manufacture and immune responses in metastatic castration-resistant prostate cancer (mCRPC) patients.
Antagonizing CD105 and androgen receptor to target stromal-epithelial interactions for clinical benefit. [2023]Androgen receptor signaling inhibitors (ARSIs) are standard of care for advanced prostate cancer (PCa) patients. Eventual resistance to ARSIs can include the expression of androgen receptor (AR) splice variant, AR-V7, expression as a recognized means of ligand-independent androgen signaling. We demonstrated that interleukin (IL)-6-mediated AR-V7 expression requires bone morphogenic protein (BMP) and CD105 receptor activity in both PCa and associated fibroblasts. Chromatin immunoprecipitation supported CD105-dependent ID1- and E2F-mediated expression of RBM38. Further, RNA immune precipitation demonstrated RBM38 binds the AR-cryptic exon 3 to enable AR-V7 generation. The forced expression of AR-V7 by primary prostatic fibroblasts diminished PCa sensitivity to ARSI. Conversely, downregulation of AR-V7 expression in cancer epithelia and associated fibroblasts was achieved by a CD105-neutralizing antibody, carotuximab. These compelling pre-clinical findings initiated an interventional study in PCa patients developing ARSI resistance. The combination of carotuximab and ARSI (i.e., enzalutamide or abiraterone) provided disease stabilization in four of nine assessable ARSI-refractory patients. Circulating tumor cell evaluation showed AR-V7 downregulation in the responsive subjects on combination treatment and revealed a three-gene panel that was predictive of response. The systemic antagonism of BMP/CD105 signaling can support ARSI re-sensitization in pre-clinical models and subjects that have otherwise developed resistance due to AR-V7 expression.
Phase I and clinical pharmacology of a type I and II, 5-alpha-reductase inhibitor (LY320236) in prostate cancer: elevation of estradiol as possible mechanism of action. [2019]To study the safety, pharmacokinetics, biologic activity, and preliminary efficacy of the bispecific 5-alpha-reductase inhibitor (LY320236) in prostate cancer.