Platform Study for Prostate Researching Translational Endpoints Correlated to Response to Inform Use of Novel Combinations

NCT03835533 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: PICI0033
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 6

Brief Summary

This study is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of immunotherapy combinations in participants with mCRPC who have received prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Metastatic Castration-resistant Prostate Cancer; Immunotherapy; Platform study; NKTR-214; Nivolumab; CDX-301; Poly-ICLC; INO-5151

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  An AE is any event that either occurs after the initiation of study drug, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, regardless of its relation to the drug. An SAE is any AE that suggests a significant hazard, contraindication, side effect, or untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Investigators recorded AEs during each participant interaction. Prior to initiation of study drug, only SAEs that were related to a protocol-mandated intervention were recorded. The AE row includes all participants who experienced at least one AE, including SAEs.

  For AEs, from initiation of study drug through 100 days after last dose, up to 24 months. For SAEs, from signing informed consent (prior to Screening) through 100 days after last dose, up to 24 months.

Secondary Outcomes (5)

• Composite Response Rate (CRR)

  Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

• Disease Control Rate (DCR)

  Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

• Radiographic Progression-free Survival (rPFS)

  Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

• Overall Survival (OS)

  From initiation of study drug until death due to any cause, up to 2.5 years

• Overall Survival (OS) at 12 Months

  At 12 months

Study Arms (3)

Cohort A: NKTR-214 + Nivolumab

EXPERIMENTAL

Drug: NKTR-214 (Cohort A); Drug: Nivolumab (Cohort A, B and C)

Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab

EXPERIMENTAL

Drug: Nivolumab (Cohort A, B and C); Radiation: Stereotactic body radiation therapy (SBRT) (Cohort B); Drug: CDX-301 (Cohort B and C); Drug: Poly-ICLC (Cohort B)

Cohort C: CDX-301 + INO-5151 + Nivolumab

EXPERIMENTAL

Drug: Nivolumab (Cohort A, B and C); Drug: CDX-301 (Cohort B and C); Drug: INO-5151 (Cohort C); Device: Cellectra 2000

Interventions

NKTR-214 (Cohort A) DRUG

NKTR-214 will be administered intravenously every 3 weeks for up to 2 years

Cohort A: NKTR-214 + Nivolumab

Nivolumab (Cohort A, B and C) DRUG

Nivolumab will be administered intravenously every 3 weeks for up to 2 years to cohort A, every 4 weeks for up to 2 years for cohort B and C.

Also known as: Opdivo

Cohort A: NKTR-214 + Nivolumab; Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab; Cohort C: CDX-301 + INO-5151 + Nivolumab

Stereotactic body radiation therapy (SBRT) (Cohort B) RADIATION

Radiation therapy will be administered at 30 - 50 Gy in 1 - 5 doses, starting on Day 1 or 2 of Cycle 1

Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab

CDX-301 (Cohort B and C) DRUG

CDX-301 will be subcutaneously once a day for 5 days for cohort B. CDX-301 will be subcutaneously once a day for 10 days of immune-priming lead-in for cohort C.

Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab; Cohort C: CDX-301 + INO-5151 + Nivolumab

Poly-ICLC (Cohort B) DRUG

Poly-ICLC will be administered intramuscularly twice weekly for 3 weeks starting on Day 1 of Cycle 1

Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab

INO-5151 (Cohort C) DRUG

INO-5151 will be administered intramuscularly on Day 8 of the Immune-priming Lead-in, and on day 1 of Cycle 1, 2 and 3, then every 12 weeks thereafter

Cohort C: CDX-301 + INO-5151 + Nivolumab

Cellectra 2000 DEVICE

Electroporation device

Cohort C: CDX-301 + INO-5151 + Nivolumab

Eligibility Criteria

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

You may qualify if:

• Metastatic castration resistant prostate cancer with castrate-level testosterone (\< 50 ng/dL) at screening.
• Disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
• Provide fresh pre-treatment core needle or incisional biopsy of a metastatic tumor lesion not previously irradiated. Fine needle aspiration is not acceptable.
• Additionally, if a pre-treatment biopsy is not medically feasible for participants with bone only disease, formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be provided.
• For all participants, in addition to fresh pre-treatment biopsy, consent for archival tissue is required.
• Must be willing to undergo tumor biopsy(ies) on treatment, if medically feasible.
• Have received and progressed on prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).
• Participants must discontinue antiandrogen therapy (ie, bicalutamide, flutamide, nilutamide) at least 4-6 weeks prior to registration with no evidence of prostate-specific antigen (PSA) decline after washout.
• Bicalutamide: Washout period at least 6 weeks
• Flutamide and nilutamide: Washout period at least 4 weeks
• Participants must discontinue therapies for mCRPC for 5 half-lives or 28 days, whichever is shorter.
• Participants will remain on gonadotropin-releasing hormone (GnRH) agents throughout this study.
• Prior chemotherapy is allowed if no progression of disease on chemotherapy as defined by PCWG3-modified RECIST 1.1.
• Prior treatment with sipuleucel-T, radium-223, or poly ADP ribose polymerase (PARP) inhibitor (eg, olaparib) is allowed.
• Tissue biopsy may be performed during washout period.

You may not qualify if:

• Has a diagnosis of immunodeficiency or conditions that need systemic corticosteroid replacement therapy \> 10 mg/day prednisone (or equivalent) or other immunosuppressive medications within 28 days prior to the first dose of study intervention. Inhaled steroids are permitted if necessary.
• Has any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring systemic treatment, or other conditions under control are permitted to enroll.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Known history of testing positive for human immunodeficiency virus (HIV), known acquired immunodeficiency syndrome (AIDS), or any positive test for hepatitis B or hepatitis C virus representing acute or chronic disease.
• Has received a live vaccine within 30 days of planned start of study intervention.
• Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study intervention. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

Sponsors & Collaborators

• Parker Institute for Cancer Immunotherapy: lead
• Bristol-Myers Squibb: collaborator
• Celldex Therapeutics: collaborator
• Cancer Research Institute, New York City: collaborator
• Inovio Pharmaceuticals: collaborator
• Oncovir, Inc.: collaborator

Study Sites (6)

Angeles Clinic

Los Angeles, California, 90025, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (23)

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MeSH Terms

Interventions

bempegaldesleukin; Nivolumab; Radiosurgery; poly ICLC

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Ute Dugan
• Organization: Parker Institute for Cancer Immunotherapy

udugan@parkerici.org

203-379-6757

Study Officials

• Parker Institute for Cancer Immunotherapy

  Parker Institute for Cancer Immunotherapy

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2019
• First Posted: February 8, 2019
• Study Start: June 21, 2019
• Primary Completion: October 3, 2022
• Study Completion: October 3, 2022
• Last Updated: April 12, 2024
• Results First Posted: April 12, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)