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

October 24, 2023 updated by: Parker Institute for Cancer Immunotherapy

A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, non-randomized, exploratory platform protocol designed to assess the safety and antitumor activity of multiple immunotherapy combinations in participants with mCRPC who have received prior therapy. The platform study will consist of 2 stages: Stage 1, an initial stage to evaluate safety, biomarkers, and clinical activity of a combination and Stage 2, an expanded cohort, when warranted, based on the safety, clinical activity, and/or biomarker results from Stage 1. The Sponsor intends to modify and/or add new combinations to the protocol as data emerge from this and other trials.

Participants must provide consent for archival tissue from a prior biopsy or surgery for prostate cancer and must consent to baseline and on-treatment biopsies, if medically feasible. Participants will be assigned to receive one of the enrolling combination study interventions and will be monitored for safety and response.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90025
        • Angeles Clinic
      • San Francisco, California, United States, 94158
        • University of California San Francisco
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10029
        • Mount Sinai
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Md Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. Metastatic castration resistant prostate cancer with castrate-level testosterone (< 50 ng/dL) at screening.
  2. Disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria.

  3. Provide fresh pre-treatment core needle or incisional biopsy of a metastatic tumor lesion not previously irradiated. Fine needle aspiration is not acceptable.

    1. 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.
    2. For all participants, in addition to fresh pre-treatment biopsy, consent for archival tissue is required.
  4. Must be willing to undergo tumor biopsy(ies) on treatment, if medically feasible.
  5. Have received and progressed on prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).

  6. 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.

    1. Bicalutamide: Washout period at least 6 weeks
    2. Flutamide and nilutamide: Washout period at least 4 weeks

  7. Participants must discontinue therapies for mCRPC for 5 half-lives or 28 days, whichever is shorter.

    1. Participants will remain on gonadotropin-releasing hormone (GnRH) agents throughout this study.
    2. Prior chemotherapy is allowed if no progression of disease on chemotherapy as defined by PCWG3-modified RECIST 1.1.
    3. Prior treatment with sipuleucel-T, radium-223, or poly ADP ribose polymerase (PARP) inhibitor (eg, olaparib) is allowed.
    4. Tissue biopsy may be performed during washout period.

Key Exclusion Criteria:

  1. 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.
  2. 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.
  3. Has a known history of active TB (Bacillus Tuberculosis).
  4. Has known history of, or any evidence of active, non-infectious pneumonitis.
  5. 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.

  6. 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.

  7. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A: NKTR-214 + Nivolumab
Drug: NKTR-214 (Cohort A)
NKTR-214 will be administered intravenously every 3 weeks for up to 2 years
Drug: Nivolumab (Cohort A, B and C)
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.
Other Names:
  • Opdivo
Experimental: Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab
Drug: Nivolumab (Cohort A, B and C)
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.
Other Names:
  • Opdivo
Radiation: Stereotactic body radiation therapy (SBRT) (Cohort B)
Radiation therapy will be administered at 30 - 50 Gy in 1 - 5 doses, starting on Day 1 or 2 of Cycle 1
Drug: CDX-301 (Cohort B and C)
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.
Drug: Poly-ICLC (Cohort B)
Poly-ICLC will be administered intramuscularly twice weekly for 3 weeks starting on Day 1 of Cycle 1
Experimental: Cohort C: CDX-301 + INO-5151 + Nivolumab
Drug: Nivolumab (Cohort A, B and C)
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.
Other Names:
  • Opdivo
Drug: CDX-301 (Cohort B and C)
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.
Drug: INO-5151 (Cohort C)
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
Device: Cellectra 2000
Electroporation device

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time Frame: 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.

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Response Rate (CRR)
Time Frame: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

CRR is a composite endpoint where response is defined as a participant meeting at least one of the following:

  1. circulating tumor cells (CTC) change from unfavorable (≥ 5 cells/7.5 mL of blood) to favorable (<= 4 cells/7.5 mL of blood);
  2. ≥ 50% reduction in Prostate-Specific Antigen (PSA) from baseline, with a repeat assessment confirming the results at least 3 weeks later;
  3. Per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; >=30% decrease in the sum of the longest diameter of target lesions). A repeat tumor assessment must confirm the CR/PR results at least 3 weeks later.
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)
Time Frame: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months
Per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a complete response (CR) is defined as disappearance of all target and non-target lesions and a partial response (PR) as a >=30% decrease in the sum of the longest diameter of target lesions. A repeat tumor assessment must confirm the CR/PR results at least 3 weeks later. DCR = CR + PR + stable disease lasting at least 6 months.
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)
Time Frame: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months

Defined as time from initiation of study intervention to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first). Per Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1, radiographic progression is defined using as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new non-bone lesions, or at least 2 new bone lesions relative to the first post-treatment scan that are confirmed on a subsequent scan.

rPFS and confidence intervals were estimated using the Kaplan-Meier method.
Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months
Overall Survival (OS)
Time Frame: From initiation of study drug until death due to any cause, up to 2.5 years
Defined as the time from initiation of study invention until death due to any cause. OS and confidence intervals were estimated using the Kaplan-Meier method.
From initiation of study drug until death due to any cause, up to 2.5 years
Overall Survival (OS) at 12 Months
Time Frame: At 12 months
Defined as the overall survival probability at 12 months, calculated using the Kaplan-Meier method.
At 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Parker Institute for Cancer Immunotherapy

Collaborators

Bristol-Myers Squibb
Cancer Research Institute, New York City
Celldex Therapeutics
Oncovir, Inc.
Inovio Pharmaceuticals

Investigators

  • Study Director: Parker Institute for Cancer Immunotherapy, Parker Institute for Cancer Immunotherapy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2019

Primary Completion (Actual)

October 3, 2022

Study Completion (Actual)

October 3, 2022

Study Registration Dates

First Submitted

February 7, 2019

First Submitted That Met QC Criteria

February 7, 2019

First Posted (Actual)

February 8, 2019

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

October 24, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PICI0033

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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