Clinical trial NCT05848011: A Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 2, Randomized, Open-Label, Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2023-05-08
Enrollment: 154
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Median radiographic progression free survival (rPFS) determined by investigator review.
timeFrame: Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years
Secondary outcomes:
measure: Objective response rate (ORR) per PCWG3 criteria
timeFrame: Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years
measure: Duration of response (DoR)
timeFrame: Every 9 weeks for the first year, then every 12 weeks for up to 4 years
measure: Time to response (TTR)
timeFrame: Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years
measure: PSA50 response rate
timeFrame: Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years
measure: PSA90 response rate
timeFrame: Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years
measure: Time to PSA progression
timeFrame: Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years
measure: Duration of PSA response
timeFrame: Every 3 weeks up to 2 years, followed by every 23 weeks for up to 2 more years.
measure: Overall survival (OS)
timeFrame: Throughout the study up to 4 years
measure: Time to First Symptomatic Skeletal Event (SSE)
timeFrame: Throughout the study up to 4 years
measure: Time to pain progression using the BPI-sf questionnaire
timeFrame: Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years
measure: Pain severity using the Brief Pain Index - short form (BPI-sf) questionnaire
timeFrame: Every 3 weeks up to 2 years
measure: Pain interference using the BPI-sf questionnaire
timeFrame: Every 3 weeks up to 2 years
measure: Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire
timeFrame: Every 3 weeks up to 2 years
measure: Description of types of adverse events (AEs) between treatment groups.
timeFrame: Throughout treatment up to 27 months
measure: Lorigerlimab maximum concentration or concentration at the end of infusion (Cmax)
timeFrame: Every 21-day cycle throughout the study, for an average of 1 year.
measure: Lorigerlimab area under the concentration time curve (AUC)
timeFrame: Every 21-day cycle throughout the study, for an average of 1 year.
measure: Trough drug concentration (Ctrough or Cmin)
timeFrame: Every 21-day cycle throughout the study, for an average of 1 year.
measure: Clearance (CL)
timeFrame: Every 21-day cycle throughout the study, for an average of 1 year.
measure: Volume of distribution (Vz)
timeFrame: Every 21-day cycle throughout the study, for an average of 1 year.
measure: Terminal half-life
timeFrame: Every 21-day cycle throughout the study, for an average of 1 year.
measure: Number of participants who develop anti-drug antibodies
timeFrame: Throughout the study, up to 2 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: United Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Grand Island
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System Cancer Center
state: Virginia
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: North Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: St Leonards
country: Australia
facility: North Shore Private Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Brussel
country: Belgium
facility: Cliniques universitaires Saint-Luc (CUSL), Brussels
city: Gent
country: Belgium
facility: UZ GENT
city: Libramont
country: Belgium
facility: Centre Hospital de l'Ardenne
city: Plovdiv
country: Bulgaria
facility: Comprehensive Cancer Center
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski
city: Bordeaux
country: France
facility: Institut Bergonie
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Quimper
country: France
facility: Centre Hospitalier Quimper
city: Saint-Grégoire
country: France
facility: CHP Saint Grégoire
city: Saint-Mandé
country: France
facility: Hia Begin
city: Suresnes
country: France
facility: Hopital Foch
city: Batumi
country: Georgia
facility: LTD High Tech Hosp Medcenter
city: Tbilisi
country: Georgia
facility: First University Clinic TSMU
city: Tbilisi
country: Georgia
facility: LTD Consilium Medulla
city: Tbilisi
country: Georgia
facility: Ltd Gidmedi
city: Tbilisi
country: Georgia
facility: LtD L.M.National Urology Center
city: Tbilisi
country: Georgia
facility: LTD MMT Hospital
city: Tbilisi
country: Georgia
facility: LTD Todua Clinic
city: Tbilisi
country: Georgia
facility: Onc. Scient. Research Center
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED
city: Kraków
country: Poland
facility: Pratia McM Kraków
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock, Szpital im. Fryderyka Chopina
city: Warsaw
country: Poland
facility: LuxMed Onkologia
city: Warsaw
country: Poland
facility: Medical Concierge
city: Warsaw
country: Poland
facility: Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o., Oddział Chemioterapii
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
city: Barcelona
country: Spain
facility: H U Germans Tries i Pujol
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Parc Tauli
city: Barcelona
country: Spain
facility: Hospital Sant Pau
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia Hospitalet_ICO Hospitalet
city: Barcelona
country: Spain
facility: Vall d' Hebron Institute of Oncology (VHIO)
city: Madrid
country: Spain
facility: Hospital 12 de octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: FIVO: Instituto Valenciano de Oncología
city: Headington
country: United Kingdom
facility: Churchill Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: MacroGenics
name: Denise Casey, M.D.
role: STUDY_DIRECTOR
References: