A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors
- Conditions
- Non-small Cell Lung CancerAndrogen-Independent Prostatic CancerLaryngeal Squamous Cell CarcinomaMelanomaCastration-Resistant Prostatic CancerAndrogen-Insensitive Prostatic CancerHormone Refractory Prostatic CancerAnal CancerAnal NeoplasmHead and Neck Squamous Cell Carcinoma
- Interventions
- Biological: vobramitamab duocarmazine 2.0 mg (Arm A)Biological: vobramitamab duocarmazine 2.7 mg (Arm B)
- Registration Number
- NCT05551117
- Lead Sponsor
- MacroGenics
- Brief Summary
Study CP-MGC018-03 is an open-label, two-part, Phase 2 study. Part 1 of the study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT). ARAT includes abiraterone, enzalutamide, or apalutamide.
Participants may have received up to 1 prior docetaxel-containing regimen, but no other chemotherapy agents.
This part of the study will assess the efficacy and tolerability of vobramitamab duocarmazine (MGC018) in two experimental arms (2.0 mg/kg every 4 weeks \[Q4W\] and 2.7 mg/kg Q4W) . Approximately 100 participants will be randomized 1:1.
Part 2 of the study will enroll participants with locally advanced or metastatic solid tumors. Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab duocarmazine at a dose of 2.7 mg/kg every 4 weeks. Up to 200 participants may be enrolled in Part 2.
In both parts, vobramitamab duocarmazine will be administered intravenously (IV) in clinic on Day 1 of each 4-week cycle. Vobramitamab duocarmazine will be administered until criteria for treatment discontinuation are met. Participants will undergo regular testing for signs of disease progression using computed tomography (CT) scans, magnetic resonance imaging (MRI), bone scans, and prostate-specific antigen (PSA) blood tests. Routine examinations and blood tests will be performed and evaluated by the study doctor.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 382
- Part 1 only: Histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features.
- Part 2 only: Histologically confirmed SCC or the anus, melanoma, HNSCC, squamous NSCLC, or SCLC.
- Part 1 only: Received 1 prior ARAT for metastatic or non-metastatic, castration-sensitive or castration-resistant prostate cancer. A second ARAT regimen of <60 days used as bridging to lutetium-177 is permitted. Up to 3 total prior lines of therapy for mCRPC are permitted..
- Part 2 only: At least 1 prior line of systemic therapy for unresectable or metastatic disease and no more than 2 prior lines of cytotoxic chemotherapy. Participants with HNSCC or melanoma must have received prior PD-1 or PD-L1 inhibitor for advanced or metastatic disease.
- All participants must have ≥ 1 metastatic lesion, according to RECIST 1.1 or PCWG3 criteria, that is present on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan obtained ≤ 28 days prior to initiation of study treatment.
- All participants must have tumor progression, according to disease-specific criteria, following their most recent anti-cancer therapy.
- All participants must have and available archival or formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for participants with metastasis to internal organs
- All participants have acceptable physical condition and laboratory values.
- All participants of childbearing potential must agree to use highly effective methods of birth control.
- All participants must not be pregnant, planning to be pregnant, or breastfeeding.
- Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
- Part 1 only: Received >1 prior taxane-containing regimen for prostate cancer. A second taxane regimen of <60 days used as bridging for lutetium-177 is permitted.
- Part 1 only: Received >3 total prior therapies for mCRPC
- Part 1 only: Participants with known BRCA or ATM mutation (germline or somatic) are not eligible unless they received prior treatment with a PARP inhibitor where available, indicated and tolerated.
- Another hematologic or solid tumor ≥ stage 1 malignancy that completed surgery, last dose of radiotherapy, or last dose of systemic anti-cancer therapy ≤ 2 years from first dose of study treatment. Participants who had curative therapy for non-melanomatous skin cancer or for localized malignancy are eligible.
- Untreated, symptomatic central nervous system (CNS) metastasis.
- Prior treatment with any B7-H3 targeted agent for cancer,
- Contradictions to the use of corticosteroid treatment
- Prior stem cell, tissue, or solid organ transplant.
- Part 1 only: Use of products that have published anti-prostate cancer activity or are known to decrease PSA.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: MGC018 2.0 mg (Arm A) vobramitamab duocarmazine 2.0 mg (Arm A) MGC018 2.0 mg/kg every 4 weeks Part 1: MGC018 2.7 mg (Arm B) vobramitamab duocarmazine 2.7 mg (Arm B) MGC018 2.7 mg/kg every 4 weeks Part 2 vobramitamab duocarmazine MGC018 2.7 mg/kg every 4 weeks Part 1: Control Arm Abiraterone Patients are administered abiraterone or enzalutamide Part 1: Control Arm Enzalutamide Patients are administered abiraterone or enzalutamide
- Primary Outcome Measures
Name Time Method Part 1: Radiographic progression free survival (rPFS) as determined by the investigator Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years The landmark analysis for 6 month rPFS rate will occur when all participants on Part 1 have been on study for at least 6 months. rPFS is defined as the time from the date of randomization to the date of first documented progressive disease (PD) per Prostate Cancer Working Group 3 (PCWG3) or death from any cause, whichever occurs first.
Part 2: Objective response rate (ORR) per investigator assessment of Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years The ORR is defined as the percentage of participants in the response evaluable population who achieve a best overall response of conplete response (CR) or partial response (PR), per RECIST version 1.1 criterial CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of diameters of target lesions.
- Secondary Outcome Measures
Name Time Method Part 1: ORR per PCWG3 criteria as determined by the investigator Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years The percentage of participants experiencing a complete response (CR) or partial response (PR) to treatment. CR + PR = ORR
Part 1: Median duration of response (DoR) per PCWG3 criteria as determined by the investigator Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years The DoR will be calculated as the time from the date of initial tumor response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first.
Part 1: Tumor size change over time Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years Part 1: Prostate-specific Cancer Antigen (PSA) response rate per PCWG3 criteria Every 4 weeks throughout study participation, up to 2 years PSA response is defined as a ≥ 50% decline in PSA from baseline with PSA confirmation ≥ 3 weeks after the first documented reduction in PSA of ≥ 50%.
Part 1: Time to PSA progression per PCWG3 criteria Every 4 weeks throughout study participation, up to 2 years In participants with a decrease in PSA from baseline, PSA progression is defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥ 3 weeks later.
In participants with no decrease in PSA from baseline, PSA progression is defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline value after 12 weeks.
Time to PSA progression is defined as the time from the date of randomization to the first PSA progression.Part 1: Duration of PSA response per PCWG3 criteria Every 4 weeks throughout study participation, up to 2 years Duration of PSA response is defined as the time from the date of first documented PSA response to the earliest date of PSA progression.
Part 1: PSA percent change over time Every 4 weeks throughout study participation, up to 2 years Part 1: Time to first symptomatic skeletal event (SSE) Every 4 weeks throughout the study, up to 2 years An SSE is defined as any of the following events: new symptomatic pathological fracture, requirement for radiation therapy to relieve bone pain, spinal cord compression, or tumor-related orthopedic surgical intervention. The time to first SSE is defined as the time from the date of randomization to the first occurrence of SSE.
Number of participants with adverse event (AEs), serious AEs (SAEs), and AEs leading to study treatment discontinuation. Throughout the study, up to 2 years Number of participants who develop anti-drug antibodies Throughout the study, up to 2 years Part 2: Median DoR per investigator assessment of RECIST 1.1 criteria Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years The DoR will be calculated as the time from the date of initial tumor response (CR or PR) to the date of first documented progressive disease (PD) or death from any cause, whichever occurs first.
Part 2: Median Progression free survival (PFS) per investigator assessment of RECIST 1.1 criteria Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years PFS is defined as the time from the date of the first dose to the date of first PD per RECIST 1.1 criteria or death from any cause, whichever occurs first.
Trial Locations
- Locations (63)
Institut Catala d'Oncologia Hospitalet
🇪🇸Barcelona, Spain
Przychodnia Lekarska "KOMED"
🇵🇱Konin, Wlkp, Poland
Gustave Roussy
🇫🇷Villejuif, Val De Marne, France
CHRU Brest
🇫🇷Brest, France
Pontchartrain Cancer Center
🇺🇸Covington, Louisiana, United States
Clinique Victor Hugo
🇫🇷Le Mans, Sarthe, France
Compassionate Cancer Care Medical Group
🇺🇸Fountain Valley, California, United States
University of California Los Angeles (UCLA) Community Cancer Care
🇺🇸Los Angeles, California, United States
The University of Florida Health System - UF Health Urology - Jacksonville
🇺🇸Jacksonville, Florida, United States
Mid Florida Hematology and Oncology Center
🇺🇸Orange City, Florida, United States
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Barbara Ann Karmanos Cancer Institute - Hudson-Webber Cancer Research Center
🇺🇸Detroit, Michigan, United States
Masonic Cancer Center, University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
VA Portland Health Care Services
🇺🇸Portland, Oregon, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
University of Virginia Comprehensive Cancer Center
🇺🇸Charlottesville, Virginia, United States
Virginia Cancer Specalists
🇺🇸Fairfax, Virginia, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Ramsay Health Care - Westmead Private Hospital
🇦🇺Westmead, New South Wales, Australia
The University of Queensland (UQ) - Princess Alexandra Hospital (PAH)
🇦🇺Woolloongabba, Queensland, Australia
Cabrini Health- Malvern
🇦🇺Malvern, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Cliniques Universitaires Saint-Luc
🇧🇪Woluwe-Saint-Lambert, Brussles, Belgium
(Grand Hopital de Charleroi) GHDC
🇧🇪Charleroi, Hainaut, Belgium
Centre Hospitalier de Ardenne - Libramont - Clinique du Sein
🇧🇪Libramont, Luxembourg, Belgium
Centre Hospitalier Universitaire (CHU) - Universite Catholique de Louvain (UCL) - Namur - Site Godinne (Cliniques Universitaires UCL de Mont-Godinne)
🇧🇪Godinne, Namur, Belgium
Algemeen Ziekenhuis Maria Middelares
🇧🇪Gent, Belgium
Centre Antoine-Lacassagne
🇫🇷Nice Cedex 2, AM, France
Institut de Cancerologie Strasbourg Europe (ICANS)
🇫🇷Strasbourg, Bas Rhin, France
Institut Bergonié
🇫🇷Bordeaux, Gironde, France
Institut régional du Cancer de Montpellier - ICM Val d'Aurelle
🇫🇷Montpellier, Herault, France
Hôpital d'Instruction des Armées Bégin
🇫🇷Saint-Mandé, Ile De France, France
Hopital Foch
🇫🇷Suresnes, Ile De France, France
Centre Hospitalier Privé Saint-Grégoire
🇫🇷Saint-Grégoire, Ille Et Vilaine, France
Institut Mutualiste Montsouris
🇫🇷Paris, France
AOU San Luigi Gonzaga Oncology Department
🇮🇹Orbassano, TO, Italy
Ospedale dell'Angelo
🇮🇹Mestre, Venice, Italy
Radiation Oncology Unit, Azienda Ospedaliera Universitaria Careggi, University of Florence
🇮🇹Florence, Italy
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Azienda Provinciale per i Servizi Sanitari - Presidio Ospedaliero S. Chiara
🇮🇹Trento, Italy
Kyungpook National University Chilgok Hospital
🇰🇷Bugok, Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang, Kyonggi, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Seoul National University Hopital
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System, Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Meical Cemter
🇰🇷Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Szpital im. Fryderyka Chopina
🇵🇱Otwock, Mazowieckie, Poland
Magodent Szpital Elblaska
🇵🇱Warszawa, Mazowieckie, Poland
Medical Concierge Centrum Medyczne
🇵🇱Warszawa, Mazowieckie, Poland
Grochowski Hospital
🇵🇱Warszawa, Mazowieckie, Poland
Szpital Wojewodzki im. Mikolaja Kopernika
🇵🇱Koszalin, Zachodniopomorskie, Poland
Hospital Universitari Parc Taulí
🇪🇸Sabadell, Barcelona, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Seville, Spain
Hospital Del Mar
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Lucus Augusti
🇪🇸Lugo, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
The Royal Marsden NHS Trust
🇬🇧Sutton, Surrey, United Kingdom
Oxford University Hospitals NHS- Churchill Hospital
🇬🇧Oxford, United Kingdom