Phase II, Open-label, Single-center Study Evaluating Safety and Activity of Androgen Deprivation Therapy Followed by Chemoimmunotherapy for Newly Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

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

Sponsors

Lead sponsor: Mark Stein

Collaborator: Regeneron Pharmaceuticals

Source Columbia University
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).

Detailed Description

The slow progress for notable trials in metastatic, hormone-sensitive disease is attributed to the long duration of follow-up required, as well as the focus on time-to-event end points, i.e. overall survival, in clinical trial design. These landmark trials (CHAARTED, STAMPEDE, LATITUDE), which used overall survival as their endpoints, required, on average, 10 years from start of trial to first peer-reviewed publication. Given the challenge of using traditional measures of response (RECIST criteria) when designing prostate cancer clinical trials, the Prostate Cancer Working group 2 (PCWG2) made trial-design recommendations. One was to separate treatment outcomes into early measures of response and later time-to-event measures of progression. The goal is to shift the trial objective to capture and reflect the actual effect of the tested treatment and, in doing so, provide a more timely drug development milieu for the metastatic patient. These early measure of response end points, such as undetectable PSA with testosterone recovery, are now being actively integrated into clinical trial design.

Overall Status Recruiting
Start Date May 2019
Completion Date December 2020
Primary Completion Date September 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of Subjects Achieving Undetectable PSA at 6 months after Combination Treatment 6 months
Enrollment 20
Condition
Intervention

Intervention type: Drug

Intervention name: REGN2810

Description: 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.

Arm group label: ADT Followed by Chemoimmunotherapy

Other name: Cemiplimab

Intervention type: Drug

Intervention name: Degarelix

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

Arm group label: ADT Followed by Chemoimmunotherapy

Other name: Firmagon

Intervention type: Drug

Intervention name: Leuprolide Acetate

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

Arm group label: ADT Followed by Chemoimmunotherapy

Other name: Lupron

Intervention type: Drug

Intervention name: Docetaxel

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

Arm group label: ADT Followed by Chemoimmunotherapy

Other name: Taxotere

Eligibility

Criteria:

Inclusion Criteria:

1. Be willing and able to provide written informed consent for the trial.

2. Age ≥18 years of age on day of signing informed consent.

3. Have life expectancy > 12 months.

4. Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

5. Have histologically or cytologically confirmed prostate cancer. Rarely pathology is not available but if clinical situation confirms prostate cancer (such as prior response to androgen ablation) pathology is not required and patient can be enrolled after discussed with study Principal Investigator (PI).

6. Have metastatic disease that is either measurable or evaluable (non-measurable).

7. Have evaluable (non-measurable) or measurable disease, based on RECIST 1.1, with at least one lesion amenable to biopsy.

8. Have testosterone level ≥ 150ng/dL.

9. 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 and have shown to have no evidence of disease (PSA < 0.1 ng/dL after prostatectomy plus hormonal therapy and < 0.5 ng/dL and not have doubled above nadir after radiation therapy plus hormonal therapy) at least 12 months after completing adjuvant or neoadjuvant hormonal therapy in order to confirm hormone sensitive state.

10. Have not received any adjuvant or neoadjuvant chemotherapy or immunotherapy.

11. Have not had prior surgical orchiectomy.

12. Have not received palliative radiation within 14 days of starting ADT on study treatment.

13. Have adequate organ and marrow function as defined below:

- Leukocytes ≥3,000/microliters (mcL)

- Absolute Neutrophil Count ≥1,500/mcL

- Platelets ≥100,000

- Hemoglobin ≥ 8.0g/dL (without transfusion in past 2 weeks)

- Prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT) ≤ 1.5 upper limit of normal (ULN) (except if on therapeutic anticoagulation in which case the patient can be enrolled if stable and anti-coagulation levels are appropriate for their condition per good clinical practice).

- Aspartate aminotransferase (AST)(SGOT)/ alanine aminotransferase (ALT)(SGPT) ≤2.5 × institutional ULN

- Total bilirubin within normal institutional limits. Note: Patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g. Gilbert's syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator.

- Creatinine clearance of ≥ 30 mL/min. Creatinine clearance (CrCl) should be calculated at screening using the Cockcroft-Gault formula.

14. Agree to undergo serial tumor biopsies, unless medically contraindicated in the opinion of the treating physician, and discussed with the principal investigator

15. The effects of REGN2810 on the developing human fetus are unknown. For this reason and because REGN2810 agents [as well as other therapeutic agents used in this trial] are known to be teratogenic, men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of REGN2810 administration. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

The subject must be excluded from participating in the trial if the subject:

1. Received ADT or other hormonal agents within 6 months prior to entering the study or in the metastatic setting.

2. Received prior immunotherapy (including inhibitors of programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-CTLA4, or Sipuleucel-T).

3. Received prior chemotherapy for prostate cancer treatment.

4. Received radiation within 2 weeks prior to entering study.

5. Is receiving any other investigational agents concurrently.

6. Had a solid organ or hematologic transplant.

7. 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).

8. 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.

9. Has a diagnosed additional malignancy within 2 years prior to first dose of trial treatment with the exception of curatively treated basal cell carcinoma of the skin or squamous cell carcinoma of the skin.

10. Has a known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis.

11. Peripheral neuropathy must be ≤ grade 1.

12. Has an active infection requiring systemic therapy.

13. 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.

14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

15. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

16. Has untreated active Hepatitis B (HBV).

17. Has dual infection with HBV/Hepatitis C Virus (HCV) or other hepatitis combinations at study entry.

18. Has received a live vaccine within 30 days of planned start of study therapy (Cycle 1, Day 1). Note: The killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.

19. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 must be excluded.

Gender: Male

Minimum age: 18 Years

Maximum age: 99 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Mark Stein, MD Principal Investigator Associate Professor of Medicine
Overall Contact

Last name: Lisa Olmos, RN

Phone: 212-342-5162

Email: [email protected]

Location
facility status contact investigator Columbia University Irving Medical Center Mark Stein, MD [email protected] Mark Stein, MD Principal Investigator
Location Countries

United States

Verification Date

May 2019

Responsible Party

Responsible party type: Sponsor-Investigator

Investigator affiliation: Columbia University

Investigator full name: Mark Stein

Investigator title: Associate Clinical Professor of Medical Oncology

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: ADT Followed by Chemoimmunotherapy

Arm group type: Experimental

Description: 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.

Patient Data No
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov