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

Immunotherapy Clinical Trial

Official title:

A Phase 2, Randomized, Open-Label, Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05848011
• Other study ID #: CP-MGD019-02
• Status: Recruiting
• Phase: Phase 2
• Start date: September 28, 2023
• Est. completion date: September 2027

Study information

• Verified date: April 2024
• Source: MacroGenics
• Contact: Global Trial Manager
• Phone: 301-251-5172
• Email: info[@]macrogenics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 2027
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Immune Checkpoint Inhibitor
• Immunotherapy
• Prostate Cancer Recurrent
• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant

Intervention

Biological:
• lorigerlimab
Lorigerlimab is a DART® molecule that binds PD-1 and CTLA-4

Drug:
• docetaxel
Docetaxel Injection is a cytotoxic anticancer drug approved to treat prostate cancer
• Prednisone
A corticosteroid drug approved for use with docetaxel in the treatment of prostate cancer

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	North Melbourne
Belgium	Cliniques universitaires Saint-Luc (CUSL), Brussels	Brussel
Belgium	UZ GENT	Gent
Belgium	Centre Hospital de l'Ardenne	Libramont
Belgium	CHU de Liège	Liège
Bulgaria	MHAT Dr. Tota Venkova	Gabrovo
Bulgaria	Comprehensive Cancer Center	Plovdiv
Bulgaria	UMHAT Sv. Ivan Rilski	Sofia
France	Institut Bergonie	Bordeaux
France	Clinique Victor Hugo	Le Mans
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
Georgia	LTD High Tech Hosp Medcenter	Batumi
Georgia	First University Clinic TSMU	Tbilisi
Georgia	LTD Consilium Medulla	Tbilisi
Georgia	LtD L.M.National Urology Center	Tbilisi
Georgia	LTD MMT Hospital	Tbilisi
Georgia	LTD Todua Clinic	Tbilisi
Georgia	Onc. Scient. Research Center	Tbilisi
Poland	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. Rafala Masztaka Sp. z o.o., Oddzial Chemioterapii	Warsaw
Puerto Rico	Pan American Center for Oncology Trials, LLC	Rio Piedras
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Parc Tauli	Barcelona
Spain	Hospital Sant Pau	Barcelona
Spain	Hospital 12 de octubre	Madrid
Spain	Hospital Beata Maria Ana	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	FIVO: Instituto Valenciano de Oncología	Valencia
United Kingdom	Churchill Hospital	Headington
United Kingdom	Charing Cross Hospital	London
United Kingdom	Royal Marsden Hospital	Sutton
United Kingdom	Musgrove Park Hospital	Taunton
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia Health System Cancer Center	Charlottesville	Virginia
United States	Nebraska Cancer Specialists	Grand Island	Nebraska
United States	MD Anderson Cancer Center	Houston	Texas
United States	United Medical Group	Miami	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	START Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  France,  Georgia,  Poland,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years
Secondary	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	Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years
Secondary	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.	Every 9 weeks for the first year, then every 12 weeks for up to 4 years
Secondary	Time to response (TTR)	TTR is defined as the time from the start of treatment to the first objective response (CR or PR).	Every 9 weeks for the first year, followed by every 12 weeks for up to 3 more years
Secondary	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%.	Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years
Secondary	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%.	Every 3 weeks up to 2 years, followed by every 12 weeks for up to 2 more years
Secondary	Time to PSA progression	Time to PSA progression is defined as the time from the date of randomization to the first documented PSA progression.	Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years
Secondary	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.	Every 3 weeks up to 2 years, followed by every 23 weeks for up to 2 more years.
Secondary	Overall survival (OS)	OS is defined as the time from the date of randomization to the date of death from any cause.	Throughout the study up to 4 years
Secondary	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.	Throughout the study up to 4 years
Secondary	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.	Every 9 weeks for the first year, followed by every 12 weeks for up to 2 more years
Secondary	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.	Every 3 weeks up to 2 years
Secondary	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.	Every 3 weeks up to 2 years
Secondary	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.	Every 3 weeks up to 2 years
Secondary	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	Throughout treatment up to 27 months
Secondary	Lorigerlimab maximum concentration or concentration at the end of infusion (Cmax)	The highest measured concentration of lorigerlimab in the bloodstream.	Every 21-day cycle throughout the study, for an average of 1 year.
Secondary	Lorigerlimab area under the concentration time curve (AUC)	AUC is the total amount of lorigerlimab in bloodstream after drug administration	Every 21-day cycle throughout the study, for an average of 1 year.
Secondary	Trough drug concentration (Ctrough or Cmin)	Trough concentration is the concentration measured before a subsequent dose of lorigerlimab	Every 21-day cycle throughout the study, for an average of 1 year.
Secondary	Clearance (CL)	Drug clearance is the amount of drug removed from the bloodstream by the body per unit of time	Every 21-day cycle throughout the study, for an average of 1 year.
Secondary	Volume of distribution (Vz)	The volume of distribution is related to how much drug is distributed to body tissues, or remains in the bloodstream.	Every 21-day cycle throughout the study, for an average of 1 year.
Secondary	Terminal half-life	Terminal elimination half-life is the time it takes for the concentration of the drug in plasma or serum to be reduced by 50%	Every 21-day cycle throughout the study, for an average of 1 year.
Secondary	Number of participants who develop anti-drug antibodies		Throughout the study, up to 2 years