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).
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
43
NKTR-214 will be administered intravenously every 3 weeks for up to 2 years
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.
Radiation therapy will be administered at 30 - 50 Gy in 1 - 5 doses, starting on Day 1 or 2 of Cycle 1
Angeles Clinic
Los Angeles, California, United States
University of California San Francisco
San Francisco, California, United States
Mount Sinai
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
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.
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.
Composite Response Rate (CRR)
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.
Time frame: 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)
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
Poly-ICLC will be administered intramuscularly twice weekly for 3 weeks starting on Day 1 of Cycle 1
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
Electroporation device
Oregon Health & Science University
Portland, Oregon, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Time frame: 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)
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.
Time frame: Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 20 months
Overall Survival (OS)
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.
Time frame: From initiation of study drug until death due to any cause, up to 2.5 years
Overall Survival (OS) at 12 Months
Defined as the overall survival probability at 12 months, calculated using the Kaplan-Meier method.
Time frame: At 12 months