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

Phase 2Active Not RecruitingNCT05848011

MacroGenics154 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

154

Conditions

Androgen-Independent Prostatic Cancer

Interventions

lorigerlimabBIOLOGICAL

Lorigerlimab is a DART® molecule that binds PD-1 and CTLA-4

docetaxelDRUG

Docetaxel Injection is a cytotoxic anticancer drug approved to treat prostate cancer

PrednisoneDRUG

A corticosteroid drug approved for use with docetaxel in the treatment of prostate cancer

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (49)

United Medical Group

Miami, Florida, United States

Orlando Health Cancer Institute

Orlando, Florida, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Nebraska Cancer Specialists

Grand Island, Nebraska, United States

MD Anderson Cancer Center

Houston, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years

Secondary Outcomes

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

Time frame: 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.

Time frame: 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).

Time frame: 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%.

Time frame: 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%.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Every 3 weeks up to 2 years

Description 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

Time frame: 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.