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

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

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 Overview

• Status: Recruiting
• Conditions: Prostate Cancer Recurrent; Immunotherapy; Androgen-Independent Prostatic Cancer; Androgen-Resistant Prostatic Cancer; Hormone Refractory Prostatic Cancer; Immune Checkpoint Inhibitor; Androgen-Independent Prostatic Neoplasms; Androgen-Insensitive Prostatic Cance; Inhibitory Checkpoint Molecule
• Intervention / Treatment: Biological: lorigerlimab; Drug: docetaxel; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Global Trial Manager; Phone Number: 301-251-5172; Email: info@macrogenics.com

Study Locations

• Australia
  • North Melbourne, Australia
    • Recruiting
    • Peter Maccallum Cancer Centre
    • Principal Investigator: Shahneen Sandhu
• Belgium
  • Brussel, Belgium
    • Recruiting
    • Cliniques universitaires Saint-Luc (CUSL), Brussels
    • Principal Investigator: Jean Pascal Machiels
  • Gent, Belgium
    • Recruiting
    • UZ Gent
    • Principal Investigator: Sylvie Rottey
  • Libramont, Belgium
    • Recruiting
    • Centre Hospital de l'Ardenne
    • Principal Investigator: Frederic Forget
  • Liège, Belgium
    • Recruiting
    • CHU de Liege
    • Principal Investigator: Brieuc Sautois
• Bulgaria
  • Gabrovo, Bulgaria
    • Recruiting
    • MHAT Dr. Tota Venkova
    • Principal Investigator: Bonka Popova
  • Plovdiv, Bulgaria
    • Recruiting
    • Comprehensive Cancer Center
    • Principal Investigator: Antoaneta Tomova
  • Sofia, Bulgaria
    • Recruiting
    • UMHAT Sv. Ivan Rilski
    • Principal Investigator: Bozhil Robev
• France
  • Bordeaux, France
    • Recruiting
    • Institut Bergonie
    • Principal Investigator: Guilhem Roubaud
  • Le Mans, France
    • Recruiting
    • Clinique Victor Hugo
    • Principal Investigator: Eric Voog
  • Nice, France
    • Recruiting
    • Centre Antoine Lacassagne
    • Principal Investigator: Delphine Borchiellini
  • Paris, France
    • Recruiting
    • Institut Mutualiste Montsouris
    • Principal Investigator: Mostefa Bennamoun
  • Quimper, France
    • Recruiting
    • Centre Hospitalier Quimper
    • Principal Investigator: Friederike Schlurmann
  • Saint-Grégoire, France
    • Recruiting
    • CHP Saint Gregoire
    • Principal Investigator: Xavier Artignan
  • Saint-Mandé, France
    • Recruiting
    • HIA Bégin
    • Principal Investigator: Carole Helissey
  • Suresnes, France
    • Recruiting
    • Hopital Foch
    • Principal Investigator: Raffaele Ratta
  • Villejuif, France
    • Recruiting
    • Institut Gustave Roussy
    • Principal Investigator: Alice Bernard Tessier
• Georgia
  • Batumi, Georgia
    • Recruiting
    • LTD High Tech Hosp Medcenter
    • Principal Investigator: Tamta Makharadze
  • Tbilisi, Georgia
    • Recruiting
    • LTD Consilium Medulla
    • Principal Investigator: Giorgi Adeishvili
  • Tbilisi, Georgia
    • Recruiting
    • LTD MMT Hospital
    • Principal Investigator: Guram Karazanashvili
  • Tbilisi, Georgia
    • Recruiting
    • LTD Todua Clinic
    • Principal Investigator: Tamar Melkadze
  • Tbilisi, Georgia
    • Recruiting
    • First University Clinic TSMU
    • Principal Investigator: David Kochiashvili
  • Tbilisi, Georgia
    • Recruiting
    • LtD L.M.National Urology Center
    • Principal Investigator: Archil Chkhotua
  • Tbilisi, Georgia
    • Recruiting
    • Onc. Scient. Research Center
    • Principal Investigator: Amiran Matitashvili
• Poland
  • Konin, Poland
    • Recruiting
    • Przychodnia Lekarska KOMED
    • Principal Investigator: Bogusława Karaszewska
  • Kraków, Poland
    • Recruiting
    • Pratia MCM Krakow
    • Principal Investigator: Bożena Cybulska-Stopa
  • Warsaw, Poland
    • Recruiting
    • LuxMed Onkologia
    • Principal Investigator: Jakub Żołnierek
  • Warsaw, Poland
    • Recruiting
    • Medical Concierge
    • Principal Investigator: Piotr Radziszewski
  • Warsaw, Poland
    • Recruiting
    • Szpital Grochowski im. dr med. Rafała Masztaka Sp. z o.o., Oddział Chemioterapii
    • Principal Investigator: Iwona Skoneczna
• Puerto Rico
  • Rio Piedras, Puerto Rico
    • Recruiting
    • Pan American Center for Oncology Trials, LLC
    • Principal Investigator: Josselyn Molina-Avila
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital del Mar
    • Principal Investigator: Alejo Rodríguez-Vida
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic de Barcelona
    • Principal Investigator: Begoña Mellado
  • Barcelona, Spain
    • Recruiting
    • Hospital Sant Pau
    • Principal Investigator: Jose Maroto
  • Madrid, Spain
    • Recruiting
    • Hospital 12 de Octubre
    • Principal Investigator: Elena Castro
  • Madrid, Spain
    • Recruiting
    • Hospital Beata Maria Ana
    • Principal Investigator: Santiago Cabezas-Camarero
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Principal Investigator: Begona Pérez Valderrama
  • Valencia, Spain
    • Recruiting
    • FIVO: Instituto Valenciano de Oncología
    • Principal Investigator: Maria Jose Juan Fita
• United Kingdom
  • Headington, United Kingdom
    • Recruiting
    • Churchill Hospital
    • Principal Investigator: Mark Tuthill
  • London, United Kingdom
    • Recruiting
    • Charing Cross Hospital
    • Principal Investigator: Naveed Sarwar
  • Sutton, United Kingdom
    • Recruiting
    • Royal Marsden Hospital
    • Principal Investigator: Johann de Bono
  • Taunton, United Kingdom
    • Recruiting
    • Musgrove Park Hospital
    • Principal Investigator: Emma Gray
• United States
  • Florida
    • Miami, Florida, United States, 33135
      • Recruiting
      • United Medical Group
      • Principal Investigator: Alvaro Ocampo
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Orlando Health Cancer Institute
      • Principal Investigator: Hatem Hassanein
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: Xiao Wei
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Recruiting
      • Nebraska Cancer Specialists
      • Principal Investigator: Ralph Hauke, MD, FACP
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Sumit Subudhi
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region
      • Principal Investigator: Joseph Call, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia Health System Cancer Center
      • Principal Investigator: William Skelton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lorigerlimab + Docetaxel and 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).	Biological: lorigerlimab; Lorigerlimab is a DART® molecule that binds PD-1 and CTLA-4; Other Names: MGD019; Drug: docetaxel; Docetaxel Injection is a cytotoxic anticancer drug approved to treat prostate cancer; Other Names: Taxotere®; Drug: Prednisone; A corticosteroid drug approved for use with docetaxel in the treatment of prostate cancer
Other: Standard of care docetaxel and prednisone; Docetaxel 75 mg/m^2 IV every 3 weeks and prednisone 5 mg orally twice daily.(up to 7 months)	Drug: docetaxel; Docetaxel Injection is a cytotoxic anticancer drug approved to treat prostate cancer; Other Names: Taxotere®; Drug: Prednisone; A corticosteroid drug approved for use with docetaxel in the treatment of prostate cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who develop anti-drug antibodies		Throughout the study, up to 2 years
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: MacroGenics
• Investigators: Study Director: Denise Casey, M.D., MacroGenics

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: CP-MGD019-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes