A Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer
- Conditions
- Androgen-Independent Prostatic CancerAndrogen-Independent Prostatic NeoplasmsProstate Cancer RecurrentAndrogen-Insensitive Prostatic CanceAndrogen-Resistant Prostatic CancerHormone Refractory Prostatic CancerImmunotherapyImmune Checkpoint InhibitorInhibitory Checkpoint Molecule
- Interventions
- Registration Number
- NCT05848011
- Lead Sponsor
- MacroGenics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 154
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of care docetaxel and prednisone docetaxel Docetaxel 75 mg/m\^2 IV every 3 weeks and prednisone 5 mg orally twice daily.(up to 7 months) Standard of care docetaxel and prednisone Prednisone Docetaxel 75 mg/m\^2 IV every 3 weeks and prednisone 5 mg orally twice daily.(up to 7 months) Lorigerlimab + Docetaxel and Prednisone lorigerlimab 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). Lorigerlimab + Docetaxel and Prednisone docetaxel 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). Lorigerlimab + Docetaxel and Prednisone 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).
- Primary Outcome Measures
Name Time Method Median radiographic progression free survival (rPFS) determined by investigator review. 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 Outcome Measures
Name Time Method 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 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
Duration of response (DoR) Every 9 weeks for the first year, then every 12 weeks for up to 4 years 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.
Time to response (TTR) Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years TTR is defined as the time from the start of treatment to the first objective response (CR or PR).
PSA50 response rate Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years 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 rate Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years 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 Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years Time to PSA progression is defined as the time from the date of randomization to the first documented PSA progression.
Duration of PSA response Every 3 weeks up to 2 years, followed by every 23 weeks for up to 2 more years. Duration of PSA response is defined as the time from the date of first PSA response to the earliest date of PSA progression.
Overall survival (OS) Throughout the study up to 4 years OS is defined as the time from the date of randomization to the date of death from any cause.
Time to First Symptomatic Skeletal Event (SSE) Throughout the study up to 4 years 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 using the BPI-sf questionnaire Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years 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.
Pain severity using the Brief Pain Index - short form (BPI-sf) questionnaire Every 3 weeks up to 2 years 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.
Pain interference using the BPI-sf questionnaire Every 3 weeks up to 2 years 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.
Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire Every 3 weeks up to 2 years 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.
Description of types of adverse events (AEs) between treatment groups. Throughout treatment up to 27 months Number of participants with adverse events (AEs), serious adverse events (SAEs), and AEs leading to study treatment discontinuation
Lorigerlimab maximum concentration or concentration at the end of infusion (Cmax) Every 21-day cycle throughout the study, for an average of 1 year. The highest measured concentration of lorigerlimab in the bloodstream.
Lorigerlimab area under the concentration time curve (AUC) Every 21-day cycle throughout the study, for an average of 1 year. AUC is the total amount of lorigerlimab in bloodstream after drug administration
Trough drug concentration (Ctrough or Cmin) Every 21-day cycle throughout the study, for an average of 1 year. Trough concentration is the concentration measured before a subsequent dose of lorigerlimab
Clearance (CL) Every 21-day cycle throughout the study, for an average of 1 year. Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time
Volume of distribution (Vz) Every 21-day cycle throughout the study, for an average of 1 year. The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream.
Terminal half-life Every 21-day cycle throughout the study, for an average of 1 year. Terminal elimination half-life is the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%
Number of participants who develop anti-drug antibodies Throughout the study, up to 2 years
Trial Locations
- Locations (58)
Institut Català d'Oncologia Hospitalet_ICO Hospitalet
🇪🇸Barcelona, Spain
Vall d' Hebron Institute of Oncology (VHIO)
🇪🇸Barcelona, Spain
Hospital 12 de octubre
🇪🇸Madrid, Spain
Hospital Parc Tauli
🇪🇸Barcelona, Spain
Hospital Sant Pau
🇪🇸Barcelona, Spain
Ltd Gidmedi
🇬🇪Tbilisi, Georgia
LtD L.M.National Urology Center
🇬🇪Tbilisi, Georgia
United Medical Group
🇺🇸Miami, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Nebraska Cancer Specialists
🇺🇸Grand Island, Nebraska, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Virginia Health System Cancer Center
🇺🇸Charlottesville, Virginia, United States
Concord Repatriation General Hospital
🇦🇺Concord, Australia
Peter MacCallum Cancer Centre
🇦🇺North Melbourne, Australia
North Shore Private Hospital
🇦🇺St Leonards, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Cliniques universitaires Saint-Luc (CUSL), Brussels
🇧🇪Brussel, Belgium
UZ GENT
🇧🇪Gent, Belgium
Centre Hospital de l'Ardenne
🇧🇪Libramont, Belgium
CHU de Liège
🇧🇪Liège, Belgium
Comprehensive Cancer Center
🇧🇬Plovdiv, Bulgaria
UMHAT Sv. Ivan Rilski
🇧🇬Sofia, Bulgaria
Institut Bergonie
🇫🇷Bordeaux, France
Clinique Victor Hugo
🇫🇷Le Mans, France
Centre Léon Bérard
🇫🇷Lyon, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Institut Mutualiste Montsouris
🇫🇷Paris, France
Centre Hospitalier Quimper
🇫🇷Quimper, France
CHP Saint Grégoire
🇫🇷Saint-Grégoire, France
Hia Begin
🇫🇷Saint-Mandé, France
Hopital Foch
🇫🇷Suresnes, France
Institut Gustave Roussy
🇫🇷Villejuif, France
LTD High Tech Hosp Medcenter
🇬🇪Batumi, Georgia
First University Clinic TSMU
🇬🇪Tbilisi, Georgia
LTD Consilium Medulla
🇬🇪Tbilisi, Georgia
LTD MMT Hospital
🇬🇪Tbilisi, Georgia
LTD Todua Clinic
🇬🇪Tbilisi, Georgia
Onc. Scient. Research Center
🇬🇪Tbilisi, Georgia
Przychodnia Lekarska KOMED
🇵🇱Konin, Poland
Pratia McM Kraków
🇵🇱Kraków, Poland
Europejskie Centrum Zdrowia Otwock, Szpital im. Fryderyka Chopina
🇵🇱Otwock, Poland
LuxMed Onkologia
🇵🇱Warsaw, Poland
Medical Concierge
🇵🇱Warsaw, Poland
Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o., Oddział Chemioterapii
🇵🇱Warsaw, Poland
Pan American Center for Oncology Trials, LLC
🇵🇷Rio Piedras, Puerto Rico
H U Germans Tries i Pujol
🇪🇸Barcelona, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Beata Maria Ana
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
FIVO: Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Churchill Hospital
🇬🇧Headington, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom