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

Study Overview
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Brief Summary
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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.

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

Conditions
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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

Intervention / Treatment
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* Biological: lorigerlimab
* Drug: docetaxel
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lorigerlimab + Docetaxel and Prednisone<br>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). | Biological: lorigerlimab<br>* Lorigerlimab is a DART® molecule that binds PD-1 and CTLA-4<br>* Other names: MGD019;Drug: docetaxel<br>* Docetaxel Injection is a cytotoxic anticancer drug approved to treat prostate cancer<br>* Other names: Taxotere®;Drug: Prednisone<br>* A corticosteroid drug approved for use with docetaxel in the treatment of prostate cancer<br>|
| Other: Standard of care docetaxel and prednisone<br>Docetaxel 75 mg/m^2 IV every 3 weeks and prednisone 5 mg orally twice daily.(up to 7 months) | Drug: docetaxel<br>* Docetaxel Injection is a cytotoxic anticancer drug approved to treat prostate cancer<br>* Other names: Taxotere®;Drug: Prednisone<br>* A corticosteroid drug approved for use with docetaxel in the treatment of prostate cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median radiographic progression free survival (rPFS) determined by investigator review. | 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. | Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) per PCWG3 criteria | 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 | Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years | 
| Duration of response (DoR) | 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. | Every 9 weeks for the first year, then every 12 weeks for up to 4 years | 
| Time to response (TTR) | TTR is defined as the time from the start of treatment to the first objective response (CR or PR). | Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years | 
| PSA50 response rate | 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%. | Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years | 
| PSA90 response rate | 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%. | Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years | 
| Time to PSA progression | Time to PSA progression is defined as the time from the date of randomization to the first documented PSA progression. | Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years | 
| Duration of PSA response | Duration of PSA response is defined as the time from the date of first PSA response to the earliest date of PSA progression. | Every 3 weeks up to 2 years, followed by every 23 weeks for up to 2 more years. | 
| Overall survival (OS) | OS is defined as the time from the date of randomization to the date of death from any cause. | Throughout the study up to 4 years | 
| Time to First Symptomatic Skeletal Event (SSE) | Time to first SSE is defined as the time from the date of randomization to the first occurrence of SSE from any cause. | Throughout the study up to 4 years | 
| Time to pain progression using the BPI-sf questionnaire | 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. | Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years | 
| Pain severity using the Brief Pain Index - short form (BPI-sf) questionnaire | 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. | Every 3 weeks up to 2 years | 
| Pain interference using the BPI-sf questionnaire | 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. | Every 3 weeks up to 2 years | 
| Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire | 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. | Every 3 weeks up to 2 years | 
| Comparison of types of adverse events (AEs) between treatment groups. | Number of participants with adverse events (AEs), serious adverse events (SAEs), and AEs leading to study treatment discontinuation | Throughout treatment up to 27 months | 
| Lorigerlimab maximum concentration or concentration at the end of infusion (Cmax) | The highest measured concentration of lorigerlimab 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) | 
| Lorigerlimab area under the concentration time curve (AUC) | AUC is the total amount of lorigerlimab in bloodstream after drug administration | 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) | 
| Trough drug concentration (Ctrough or Cmin) | Trough concentration is the concentration measured before a subsequent dose of lorigerlimab | 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) | 
| Clearance (CL) | Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time | 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) | 
| Volume of distribution (Vz) | 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 half-life | 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) | 
| Number of participants who develop anti-drug antibodies |  | Throughout the study, up to 2 years |