A Phase 2, Randomized, Open-Label, Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- docetaxel
- Conditions
- Androgen-Independent Prostatic Cancer
- Sponsor
- MacroGenics
- Enrollment
- 154
- Locations
- 108
- Primary Endpoint
- Median radiographic progression free survival (rPFS) determined by investigator review.
- Status
- Completed
- Last Updated
- 15 days ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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 shows evidence of disease progression after receiving at least 1 prior androgen receptor axis-targeted therapy (ARAT) regimen (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide).
- •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.
Arms & Interventions
Lorigerlimab + Docetaxel and Prednisone
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).
Intervention: docetaxel
Lorigerlimab + Docetaxel and Prednisone
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).
Intervention: lorigerlimab
Standard of care docetaxel and prednisone
Docetaxel 75 mg/m\^2 IV every 3 weeks and prednisone 5 mg orally twice daily.(up to 7 months)
Intervention: docetaxel
Lorigerlimab + Docetaxel and Prednisone
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).
Intervention: Prednisone
Standard of care docetaxel and prednisone
Docetaxel 75 mg/m\^2 IV every 3 weeks and prednisone 5 mg orally twice daily.(up to 7 months)
Intervention: Prednisone
Outcomes
Primary Outcomes
Median radiographic progression free survival (rPFS) determined by investigator review.
Time Frame: Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years
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.
Secondary Outcomes
- Objective response rate (ORR) per PCWG3 criteria(Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years)
- Duration of response (DoR)(Every 9 weeks for the first year, then every 12 weeks for up to 4 years)
- Time to response (TTR)(Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years)
- PSA50 response rate(Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years)
- PSA90 response rate(Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years)
- Time to PSA progression(Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years)
- Duration of PSA response(Every 3 weeks up to 2 years, followed by every 23 weeks for up to 2 more years.)
- Overall survival (OS)(Throughout the study up to 4 years)
- Time to First Symptomatic Skeletal Event (SSE)(Throughout the study up to 4 years)
- Time to pain progression using the BPI-sf questionnaire(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(Every 3 weeks up to 2 years)
- Pain interference using the BPI-sf questionnaire(Every 3 weeks up to 2 years)
- Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire(Every 3 weeks up to 2 years)
- Description of types of adverse events (AEs) between treatment groups.(Throughout treatment up to 27 months)
- Lorigerlimab maximum concentration or concentration at the end of infusion (Cmax)(Every 21-day cycle throughout the study, for an average of 1 year.)
- Lorigerlimab area under the concentration time curve (AUC)(Every 21-day cycle throughout the study, for an average of 1 year.)
- Trough drug concentration (Ctrough or Cmin)(Every 21-day cycle throughout the study, for an average of 1 year.)
- Clearance (CL)(Every 21-day cycle throughout the study, for an average of 1 year.)
- Volume of distribution (Vz)(Every 21-day cycle throughout the study, for an average of 1 year.)
- Terminal half-life(Every 21-day cycle throughout the study, for an average of 1 year.)
- Number of participants who develop anti-drug antibodies(Throughout the study, up to 2 years)