REGN4336 + Cemiplimab for Prostate Cancer
Palo Alto (17 mi)Age: 18+
Sex: Male
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Regeneron Pharmaceuticals
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.
Is the drug Cemiplimab, also known as REGN4336, a promising treatment for prostate cancer?Cemiplimab, also known as REGN4336, is a promising drug for prostate cancer because it is part of a new type of treatment called bispecific antibodies. These antibodies can target prostate cancer cells specifically, potentially offering a new way to fight the disease when other treatments are not effective.145610
What safety data exists for REGN4336 + Cemiplimab in prostate cancer treatment?The provided research does not contain specific safety data for REGN4336 + Cemiplimab. It discusses other treatments like the bispecific PSMAxCD3 antibody CC-1, Sipuleucel-T, Atezolizumab, and immune checkpoint inhibitors in prostate cancer, but not REGN4336 or Cemiplimab specifically.45789
What data supports the idea that REGN4336 + Cemiplimab for Prostate Cancer is an effective treatment?The available research does not provide specific data supporting the effectiveness of REGN4336 + Cemiplimab for prostate cancer. Instead, it discusses the challenges and current status of using similar treatments, like bispecific antibodies, in prostate cancer therapy. These treatments are still in development and have not yet shown success in solid tumors like prostate cancer. Other treatments, such as newer hormonal agents and cancer vaccines, have been approved for use in advanced prostate cancer, but the effectiveness of REGN4336 + Cemiplimab specifically is not detailed in the provided information.23456
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received treatment with an approved systemic therapy within 3 weeks of dosing, or any previous systemic biologic or immune-modulating therapy within 5 half-lives of the first dose of study therapy. Also, ongoing corticosteroid therapy over 10 mg prednisone/day is not allowed within 1 week prior to the first dose.
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 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.
I do not have an uncontrolled HIV, hepatitis B or C, or an immunodeficiency.
I've had cancer treatment within the last 3 weeks or am still recovering from side effects.
Treatment Details
The 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.
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
Thomas Jefferson University, Sidney Kimmel Center, Clinical Research OrganizationPhiladelphia, PA
More Trial Locations
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Who is running the clinical trial?
Regeneron PharmaceuticalsLead Sponsor
References
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.
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.
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.
Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study. [2022]Atezolizumab [anti-programmed death-ligand 1 (anti-PD-L1)] is well tolerated and efficacious in multiple cancers, but has not been previously evaluated in metastatic castration-resistant prostate cancer (mCRPC). This study examined the safety, efficacy, and biomarkers of atezolizumab monotherapy for mCRPC.
Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach. [2023]Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.
A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. [2023]Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride (radium-223) in men with mCRPC.
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.