REGN2810 Followed by Chemoimmunotherapy for Newly Metastatic Hormone-sensitive Prostate Cancer

NCT03951831 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAS1863
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to determine the safety and activity of combined hormonal chemoimmunotherapy in a single-arm phase II trial of REGN2810, androgen deprivation therapy (ADT), and docetaxel in patients with newly metastatic, hormone-sensitive prostate cancer (mHSPC), using a primary endpoint of undetectable prostate-specific antigen (PSA) at 6 months, defined from start of combination therapy (week 10) until 6 months (week 37).

Conditions

Prostate Cancer Metastatic

Keywords

Cancer; Chemoimmunotherapy; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects Achieving Undetectable PSA at 6 months after Combination Treatment

  The percentage of subject achieving undetectable PSA levels at 6 months after the combination will use measured to determine safety and activity of combined hormonal chemoimmunotherapy.

  6 months

Secondary Outcomes (2)

• Time to Development of Castrate Resistance

  6 months

• Radiographic Response

  6 months

Study Arms (1)

ADT Followed by Chemoimmunotherapy

EXPERIMENTAL

REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.

Drug: REGN2810; Drug: Degarelix; Drug: Leuprolide Acetate; Drug: Docetaxel

Interventions

REGN2810 DRUG

Cemiplimab (REGN 2810) is administered starting at week 4 at a dose of 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease.

Also known as: Cemiplimab

ADT Followed by Chemoimmunotherapy

Degarelix DRUG

Degarelix is administered subcutaneously (SC) at a dose of 240mg once.

Also known as: Firmagon

ADT Followed by Chemoimmunotherapy

Leuprolide Acetate DRUG

Leuprolide acetate is provided at a dose of 22.5mg SC every 3 months.

Also known as: Lupron

ADT Followed by Chemoimmunotherapy

Docetaxel DRUG

Docetaxel is administered starting at week 10 at a dose of 75 mg/m2 every 21 days for up to 6 cycles.

Also known as: Taxotere

ADT Followed by Chemoimmunotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Age ≥18 years of age on day of signing informed consent.
• Have life expectancy \> 12 months.
• Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Have histologically or cytologically confirmed prostate cancer from prostate biopsy, radical prostatectomy, TURP or from biopsy of a metastatic site. Rarely pathology is not available but if clinical situation confirms prostate cancer (such as prior response to androgen ablation and/or metastatic disease typical of prostate cancer, i.e. involving bone or pelvic/extra pelvic lymph nodes or para-aortic lymph nodes, AND an elevated serum concentration of PSA typical of prostate cancer) pathology is not required and patient can be enrolled after discussed with study PI..
• Have metastatic disease that is either measurable or evaluable (non-measurable).
• Have evaluable (non-measurable) or measurable disease, based on RECIST 1.1, with at least one lesion amenable to biopsy.
• Have testosterone level ≥ 150ng/dL.
• Have not been on androgen deprivation therapy or novel hormonal agents (e.g., abiraterone, enzalutamide, apalutamide) for at least 6 months prior to enrollment in trial and must not have exceeded 24 months of therapy
• Have not received any adjuvant or neoadjuvant chemotherapy or immunotherapy.
• Have not had prior bilateral surgical orchiectomy.
• Have not received palliative radiation within 14 days of starting ADT on study treatment.
• Have adequate organ and marrow function as defined below:
• Leukocytes ≥3,000/microliters (mcL)
• Absolute Neutrophil Count ≥1,500/mcL

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Received ADT or other hormonal agents within 6 months prior to entering the study or in the metastatic setting with the exception of 5-alpha reductase inhibitors (e.g.
• finasteride and dutasteride) and first-generation androgen receptor inhibitor (e.g.
• bicalutamide) in setting of normal testosterone. Advise subject to continue the 5-alpha reductase inhibitor for the duration of the study if already started. Advise subject to stop the androgen receptor inhibitor for duration of the study
• Received prior immunotherapy (including inhibitors of programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-CTLA4, or Sipuleucel-T).
• Received prior chemotherapy for prostate cancer treatment.
• Received radiation within 2 weeks prior to entering study.
• Is receiving any other investigational agents concurrently.
• Had a solid organ or hematologic transplant.
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a diagnosed malignant disease, other than the tumor type being treated in this study. Note: Patients with a prior or concurrent malignancy of low metastatic potential that does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included (e.g., patients with a history of nonmelanoma skin cancer, carcinoma in situ of the cervix, early stage cancers treated with curative intent, non-muscle invasive bladder cancer, stage I renal cancer)Has a known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis.
• Peripheral neuropathy must be ≤ grade 1
• Has an active infection requiring systemic therapy.
• Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including dialysis.

Sponsors & Collaborators

• Mark Stein: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Hawley JE, Obradovic AZ, Dallos MC, Lim EA, Runcie K, Ager CR, McKiernan J, Anderson CB, Decastro GJ, Weintraub J, Virk R, Lowy I, Hu J, Chaimowitz MG, Guo XV, Zhang Y, Haffner MC, Worley J, Stein MN, Califano A, Drake CG. Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer. Cancer Cell. 2023 Nov 13;41(11):1972-1988.e5. doi: 10.1016/j.ccell.2023.10.006. Epub 2023 Nov 2.

  PMID: 37922910 DERIVED

MeSH Terms

Conditions

Neoplasms; Prostatic Neoplasms

Interventions

cemiplimab; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Leuprolide; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Mark N. Stein, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Clinical Professor of Medical Oncology

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 15, 2019
• Study Start: May 16, 2019
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)