Clinical Trials /

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

NCT03835533

Description:

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).

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Platform Study for Prostate Researching Translational Endpoints Correlated to Response to Inform Use of Novel Combinations
  • Official Title: A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: PICI0033
  • NCT ID: NCT03835533

Conditions

  • Metastatic Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
NKTR-214 (Cohort A)Cohort A: NKTR-214 + Nivolumab
Nivolumab (Cohort A, B and C)OpdivoCohort A: NKTR-214 + Nivolumab
CDX-301 (Cohort B and C)Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab
Poly-ICLC (Cohort B)Cohort B: SBRT + CDX-301 + Poly-ICLC + Nivolumab
INO-5151 (Cohort C)Cohort C: CDX-301 + INO-5151 + Nivolumab

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A: NKTR-214 + NivolumabExperimental
  • NKTR-214 (Cohort A)
  • Nivolumab (Cohort A, B and C)
Cohort B: SBRT + CDX-301 + Poly-ICLC + NivolumabExperimental
  • Nivolumab (Cohort A, B and C)
  • CDX-301 (Cohort B and C)
  • Poly-ICLC (Cohort B)
Cohort C: CDX-301 + INO-5151 + NivolumabExperimental
  • Nivolumab (Cohort A, B and C)
  • CDX-301 (Cohort B and C)
  • INO-5151 (Cohort C)

Eligibility Criteria

        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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events
Time Frame:Up to 2.5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 2.5 years
Safety Issue:
Description:ORR is a composite endpoint where response is defined as a participant meeting at least one of the following: circulating tumor cells change from unfavorable to favorable ; ≥ 50% reduction in Prostate-Specific Antigen (PSA) from baseline; confirmed complete response (CR) or partial response (PR)
Measure:Disease control rate
Time Frame:At 9 months
Safety Issue:
Description:Defined as CR, PR, or stable disease (SD) for 9 months as best response by Prostate Cancer Clinical Trials Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Measure:Radiographic progression-free survival (rPFS)
Time Frame:Up to 2.5 years
Safety Issue:
Description: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)
Measure:Overall survival (OS)
Time Frame:Up to 2.5 years
Safety Issue:
Description:Defined as the time from initiation of study invention until death due to any cause
Measure:Overall survival (OS) at 12 months
Time Frame:At 12 months
Safety Issue:
Description:Defined as the time from initiation of study invention until death due to any cause

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Parker Institute for Cancer Immunotherapy

Trial Keywords

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

Last Updated