Clinical trial NCT05551117: A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors
Official title: A Phase 2, Open-label, Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Castration-Resistant Prostatic Cancer
Androgen-Independent Prostatic Cancer
Androgen-Insensitive Prostatic Cancer
Androgen-Resistant Prostatic Cancer
Hormone Refractory Prostatic Cancer
Anal Cancer
Anal Neoplasm
Carcinoma, Squamous Cell of Head and Neck
Head and Neck Squamous Cell Carcinoma
Laryngeal Squamous Cell Carcinoma
Oral Squamous Cell Carcinoma
Malignant Melanoma
Melanoma
Non-small Cell Lung Cancer
Non-small Cell Carcinoma
Small-cell Lung Cancer
Small Cell Carcinoma
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2022-09-22
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Part 1: Radiographic progression free survival (rPFS) as determined by the investigator
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
measure: Part 2: Objective response rate (ORR) per investigator assessment of Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
Secondary outcomes:
measure: Part 1: ORR per PCWG3 criteria as determined by the investigator
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
measure: Part 1: Median duration of response (DoR) per PCWG3 criteria as determined by the investigator
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
measure: Part 1: Tumor size change over time
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
measure: Part 1: Prostate-specific Cancer Antigen (PSA) response rate per PCWG3 criteria
timeFrame: Every 4 weeks throughout study participation, up to 2 years
measure: Part 1: Time to PSA progression per PCWG3 criteria
timeFrame: Every 4 weeks throughout study participation, up to 2 years
measure: Part 1: Duration of PSA response per PCWG3 criteria
timeFrame: Every 4 weeks throughout study participation, up to 2 years
measure: Part 1: PSA percent change over time
timeFrame: Every 4 weeks throughout study participation, up to 2 years
measure: Part 1: Time to first symptomatic skeletal event (SSE)
timeFrame: Every 4 weeks throughout the study, up to 2 years
measure: Number of participants with adverse event (AEs), serious AEs (SAEs), and AEs leading to study treatment discontinuation.
timeFrame: Throughout the study, up to 2 years
measure: Number of participants who develop anti-drug antibodies
timeFrame: Throughout the study, up to 2 years
measure: Part 2: Median DoR per investigator assessment of RECIST 1.1 criteria
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
measure: Part 2: Median Progression free survival (PFS) per investigator assessment of RECIST 1.1 criteria
timeFrame: Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA) Community Cancer Care
state: California
city: Jacksonville
country: United States
facility: The University of Florida Health System - UF Health Urology - Jacksonville
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Covington
country: United States
facility: Pontchartrain Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute - Hudson-Webber Cancer Research Center
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Portland
country: United States
facility: VA Portland Health Care Services
state: Oregon
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specalists
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Westmead
country: Australia
facility: Ramsay Health Care - Westmead Private Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: The University of Queensland (UQ) - Princess Alexandra Hospital (PAH)
state: Queensland
city: Malvern
country: Australia
facility: Cabrini Health- Malvern
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
state: Brussles
city: Charleroi
country: Belgium
facility: (Grand Hopital de Charleroi) GHDC
state: Hainaut
city: Libramont
country: Belgium
facility: Centre Hospitalier de Ardenne - Libramont - Clinique du Sein
state: Luxembourg
city: Godinne
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) - Universite Catholique de Louvain (UCL) - Namur - Site Godinne (Cliniques Universitaires UCL de Mont-Godinne)
state: Namur
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis Maria Middelares
city: Nice Cedex 2
country: France
facility: Centre Antoine-Lacassagne
state: AM
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe (ICANS)
state: Bas Rhin
city: Bordeaux
country: France
facility: Institut Bergonié
state: Gironde
city: Montpellier
country: France
facility: Institut régional du Cancer de Montpellier - ICM Val d'Aurelle
state: Herault
city: Saint-Mandé
country: France
facility: Hôpital d'Instruction des Armées Bégin
state: Ile De France
city: Suresnes
country: France
facility: Hopital Foch
state: Ile De France
city: Saint-Grégoire
country: France
facility: Centre Hospitalier Privé Saint-Grégoire
state: Ille Et Vilaine
city: Le Mans
country: France
facility: Clinique Victor Hugo
state: Sarthe
city: Villejuif
country: France
facility: Gustave Roussy
state: Val De Marne
city: Brest
country: France
facility: CHRU Brest
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga Oncology Department
state: TO
city: Mestre
country: Italy
facility: Ospedale dell'Angelo
state: Venice
city: Florence
country: Italy
facility: Radiation Oncology Unit, Azienda Ospedaliera Universitaria Careggi, University of Florence
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Trento
country: Italy
facility: Azienda Provinciale per i Servizi Sanitari - Presidio Ospedaliero S. Chiara
city: Bugok
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
state: Daegu
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
state: Kyonggi
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hopital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Meical Cemter
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Otwock
country: Poland
facility: Szpital im. Fryderyka Chopina
state: Mazowieckie
city: Warszawa
country: Poland
facility: Magodent Szpital Elblaska
state: Mazowieckie
city: Warszawa
country: Poland
facility: Medical Concierge Centrum Medyczne
state: Mazowieckie
city: Warszawa
country: Poland
facility: Grochowski Hospital
state: Mazowieckie
city: Konin
country: Poland
facility: Przychodnia Lekarska "KOMED"
state: Wlkp
city: Koszalin
country: Poland
facility: Szpital Wojewodzki im. Mikolaja Kopernika
state: Zachodniopomorskie
city: Sabadell
country: Spain
facility: Hospital Universitari Parc Taulí
state: Barcelona
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Seville
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia Hospitalet
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Trust
state: Surrey
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS- Churchill Hospital
Study officials:
affiliation: MacroGenics
name: Liudmila Schafer, M.D.
role: STUDY_DIRECTOR
References: