Androgen-Independent Prostatic Cancer, Androgen-Independent Prostatic Neoplasms, Androgen-Insensitive Prostatic Cance, Androgen-Resistant Prostatic Cancer, Hormone Refractory Prostatic Cancer, Immune Checkpoint Inhibitor, Immunotherapy, Inhibitory Checkpoint Molecule, Prostate Cancer Recurrent
Conditions
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.
Interventions
BIOLOGICALlorigerlimab
Lorigerlimab is a DART® molecule that binds PD-1 and CTLA-4
DRUGdocetaxel
Docetaxel Injection is a cytotoxic anticancer drug approved to treat prostate cancer
DRUGPrednisone
A corticosteroid drug approved for use with docetaxel in the treatment of prostate cancer
Sponsors
MacroGenics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Australia, Belgium, Bulgaria, France, Georgia, Poland, Puerto Rico, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORPepi Pencheva, M.D.
MacroGenics
Outcome results
None listed