A Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer

A Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer

A Phase 2, Randomized, Open-Label, Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer

The purpose of this study is to determine whether the amount of time before disease progression can be prolonged in participants with metastatic castration-resistant prostate cancer (MCRPC) who receive lorigerlimab in addition to the standard of care (SOC) of docetaxel and prednisone. About 150 participants with mCRPC will be enrolled. Participants will be randomized in a 2:1 ratio to receive lorigerlimab with docetaxel and prednisone (experimental arm) or docetaxel and prednisone alone (standard-of-care arm). Lorigerlimab+docetaxel or docetaxel will be administered intravenously (IV) in clinic on Day 1 of each 3-week cycle. Prednisone will be administered orally twice daily. Lorigerlimab will be administered for up to 35 cycles. Docetaxel and prednisone will be administered up to 10 cycles until treatment discontinuation criteria are met. Participants will undergo regular testing for signs of disease progression using computed tomography (CT) scans, magnetic resonance imaging (MRI) and prostate-specific antigen (PSA) blood tests. Participants will be asked to complete questionnaires about their health and well-being. Routine examinations and blood tests will be performed and evaluated by the study doctor. Participants who have disease progression standard-of-care arm have the option of continuing on the study to receive lorigerlimab monotherapy.

Androgen-Independent Prostatic Cancer, Androgen-Independent Prostatic Neoplasms, Prostate Cancer Recurrent, Androgen-Insensitive Prostatic Cance, Androgen-Resistant Prostatic Cancer, Hormone Refractory Prostatic Cancer, Immunotherapy, Immune Checkpoint Inhibitor, Inhibitory Checkpoint Molecule

Lorigerlimab 6 mg/kg IV (up to 2 years) and docetaxel 75 mg/m^2 IV every 3 weeks (up to 7 months) and prednisone 5 mg orally twice daily (up to 7 months).

The rPFS is defined as the time from the date of randomization to the date of first documented PD per Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first.

ORR is defined as the number of participants who have a best overall response of confirmed complete response (CR) or partial response (PR) without prior confirmed bone progression

DoR is the time from the date of initial tumor response (CR or PR) to the date of first disease progression or death from any cause, whichever occurs first.

PSA50 response is defined as a ≥ 50% decline in PSA from baseline with confirmation at least 3 weeks after the first documented reduction in PSA of ≥ 50%.

PSA90 response is defined as a ≥ 90% decline in PSA from baseline with confirmation at least 3 weeks after the first documented reduction in PSA of ≥ 90%.

Time to PSA progression is defined as the time from the date of randomization to the first documented PSA progression.

Duration of PSA response is defined as the time from the date of first PSA response to the earliest date of PSA progression.

Time to first SSE is defined as the time from the date of randomization to the first occurrence of SSE from any cause.

Time to pain progression is defined as the time interval from randomization to the first date a participant experiences pain progression. Higher scores indicate more severe pain.

The BPI-sf pain severity score consists of 4 items that assess pain at its worst, least, average, and current pain intensity. The pain severity score is the average of the 4 item scores. Higher scores indicate more severe pain.

The BPI-sf pain interference score includes 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The pain interference score is the average of the 7 interference items. Higher scores indicate more interference from pain in daily life.

The FACT-P consists of 27 items from the Functional Assessment of Cancer Therapy-General (FACT-G) that measure physical, social/family, emotional, and functional well-being and 12 items that compose the Prostate Cancer Subscale (PCS). Higher scores indicate greater impact of prostate cancer on daily life.

Number of participants with adverse events (AEs), serious adverse events (SAEs), and AEs leading to study treatment discontinuation

Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, Cycle 1 Day 8, and Cycle 1 Day 15. Pre-infusion, EOI and 2-4 hours after EOI on Cycle 2 Days 1. Pre-infusion and EOI on Day 1 of Cycles 3 to 12 (21-day cycle)

Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, Cycle 1 Day 8, and Cycle 1 Day 15. Pre-infusion, EOI and 2-4 hours after EOI on Cycle 2 Days 1. Pre-infusion and EOI on Day 1 of Cycles 3 to 12 (21-day cycle)

Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, Cycle 1 Day 8, and Cycle 1 Day 15. Pre-infusion, EOI and 2-4 hours after EOI on Cycle 2 Days 1. Pre-infusion and EOI on Day 1 of Cycles 3 to 12 (21-day cycle)

Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, Cycle 1 Day 8, and Cycle 1 Day 15. Pre-infusion, EOI and 2-4 hours after EOI on Cycle 2 Days 1. Pre-infusion and EOI on Day 1 of Cycles 3 to 12 (21-day cycle)

The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream.

Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, Cycle 1 Day 8, and Cycle 1 Day 15. Pre-infusion, EOI and 2-4 hours after EOI on Cycle 2 Days 1. Pre-infusion and EOI on Day 1 of Cycles 3 to 12 (21-day cycle)

Terminal elimination half-life is the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%

Cycle 1, Day 1: Predose, end of infusion (EOI [1 hour]), 2-4 hours after EOI, Cycle 1 Day 8, and Cycle 1 Day 15. Pre-infusion, EOI and 2-4 hours after EOI on Cycle 2 Days 1. Pre-infusion and EOI on Day 1 of Cycles 3 to 12 (21-day cycle)

Inclusion Criteria: Metastatic castration-resistant adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features Participants must have ≥ 1 metastatic (measurable or non-measurable per PCWG3) lesion Participant has prostate cancer progression at study entry based on PCWG3 criteria Participant has received at least 1 and no more than 2 prior androgen receptor axis-targeted therapy (ARAT) regimens (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide) for mCRPC. Patients with known history of documented breast cancer gene (BRCA) mutation (germline or somatic) must have received an approved poly ADP ribose polymerase (PARP) inhibitor regimen Participants must have adequate performance status, life expectancy and laboratory values Exclusion Criteria: Any condition preventing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures. Received prior chemotherapy for mCRPC, prior treatment with radiopharmaceuticals, or checkpoint inhibitors for prostate cancer. Current active or chronic infections Any clinically significant heart . lung, or gastrointestinal disorders. Allergy to any of the study treatments or components of the study treatments.