A Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration Resistant Prostate Cancer and Other Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

— Tamarack  

Official title:

A Phase 2, Open-label, Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05551117
• Other study ID #: CP-MGC018-03
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 13, 2023
• Est. completion date: May 2027

Study information

• Verified date: April 2024
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 squamous cell carcinoma (SCC) of the anus, melanoma, head and neck squamous cell carcinoma (HNSCC), squamous non-small cell lung carcinoma (NSCLC), and small cell lung carcinoma (SCLC). Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab docarmazine 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 for up to 26 cycles, approximately 2 years, 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 382
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• 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.

Related Conditions & MeSH terms

• Anal Cancer
• Anal Neoplasm
• Anus Neoplasms
• Carcinoma
• Carcinoma, Small Cell
• Carcinoma, Squamous Cell
• Carcinoma, Squamous Cell of Head and Neck
• Castration-Resistant Prostatic Cancer
• Head and Neck Squamous Cell Carcinoma
• Laryngeal Squamous Cell Carcinoma
• Lung Neoplasms
• Malignant Melanoma
• Melanoma
• Non-small Cell Carcinoma
• Non-small Cell Lung Cancer
• Oral Squamous Cell Carcinoma
• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant
• Small Cell Carcinoma
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• vobramitamab duocarmazine 2.0 mg (Arm A)
2.0 mg/kg intravenous (IV) every 4 weeks
• vobramitamab duocarmazine 2.7 mg (Arm B)
2.7 mg.kg IV every 4 weeks
• vobramitamab duocarmazine
2.7 mg.kg IV every 4 weeks

Locations

Country	Name	City	State
Australia	Cabrini Health- Malvern	Malvern	Victoria
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Ramsay Health Care - Westmead Private Hospital	Westmead	New South Wales
Australia	The University of Queensland (UQ) - Princess Alexandra Hospital (PAH)	Woolloongabba	Queensland
Belgium	(Grand Hopital de Charleroi) GHDC	Charleroi	Hainaut
Belgium	Algemeen Ziekenhuis Maria Middelares	Gent
Belgium	Centre Hospitalier Universitaire (CHU) - Universite Catholique de Louvain (UCL) - Namur - Site Godinne (Cliniques Universitaires UCL de Mont-Godinne)	Godinne	Namur
Belgium	Centre Hospitalier de Ardenne - Libramont - Clinique du Sein	Libramont	Luxembourg
Belgium	Cliniques Universitaires Saint-Luc	Woluwe-Saint-Lambert	Brussles
France	Institut Bergonié	Bordeaux	Gironde
France	CHRU Brest	Brest
France	Clinique Victor Hugo	Le Mans	Sarthe
France	Institut régional du Cancer de Montpellier - ICM Val d'Aurelle	Montpellier	Herault
France	Centre Antoine-Lacassagne	Nice Cedex 2	AM
France	Institut Mutualiste Montsouris	Paris
France	Centre Hospitalier Privé Saint-Grégoire	Saint-Grégoire	Ille Et Vilaine
France	Hôpital d'Instruction des Armées Bégin	Saint-Mandé	Ile De France
France	Institut de Cancerologie Strasbourg Europe (ICANS)	Strasbourg	Bas Rhin
France	Hopital Foch	Suresnes	Ile De France
France	Gustave Roussy	Villejuif	Val De Marne
Italy	Radiation Oncology Unit, Azienda Ospedaliera Universitaria Careggi, University of Florence	Florence
Italy	Ospedale dell'Angelo	Mestre	Venice
Italy	AOU San Luigi Gonzaga Oncology Department	Orbassano	TO
Italy	Istituto Oncologico Veneto	Padova
Italy	Azienda Provinciale per i Servizi Sanitari - Presidio Ospedaliero S. Chiara	Trento
Korea, Republic of	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	Asan Medical Center	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Samsung Meical Cemter	Seoul
Korea, Republic of	Seoul National University Hopital	Seoul
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul
Poland	Przychodnia Lekarska "KOMED"	Konin	Wlkp
Poland	Szpital Wojewodzki im. Mikolaja Kopernika	Koszalin	Zachodniopomorskie
Poland	Szpital im. Fryderyka Chopina	Otwock	Mazowieckie
Poland	Grochowski Hospital	Warszawa	Mazowieckie
Poland	Magodent Szpital Elblaska	Warszawa	Mazowieckie
Poland	Medical Concierge Centrum Medyczne	Warszawa	Mazowieckie
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitari Parc Taulí	Sabadell	Barcelona
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Seville
United Kingdom	Oxford University Hospitals NHS- Churchill Hospital	Oxford
United Kingdom	The Royal Marsden NHS Trust	Sutton	Surrey
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Gabrail Cancer Center	Canton	Ohio
United States	University of Virginia Comprehensive Cancer Center	Charlottesville	Virginia
United States	Pontchartrain Cancer Center	Covington	Louisiana
United States	Barbara Ann Karmanos Cancer Institute - Hudson-Webber Cancer Research Center	Detroit	Michigan
United States	Virginia Cancer Specalists	Fairfax	Virginia
United States	Compassionate Cancer Care Medical Group	Fountain Valley	California
United States	The University of Florida Health System - UF Health Urology - Jacksonville	Jacksonville	Florida
United States	University of California Los Angeles (UCLA) Community Cancer Care	Los Angeles	California
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	VA Portland Health Care Services	Portland	Oregon
United States	Fred Hutchinson Cancer Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Italy,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Radiographic progression free survival (rPFS) as determined by the investigator	The 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. Three arms will be compared: Arm A, Arm B, and control.	Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
Primary	Part 2: Objective response rate (ORR) per investigator assessment of Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria	The ORR is defined as the percentage of participants in the response evaluable poplaiton 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.	Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
Secondary	Part 1: ORR per PCWG3 criteria as determined by the investigator	The number of participants experiencing a complete response (CR) or partial response (PR) to treatment.	as determined by the investigator
Secondary	Part 1: Duration of response (DoR) per PCWG3 criteria as determined by the investigator	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.	Every 8 weeks throughout study participation, up to 2 years
Secondary	Part 1: Prostate-specific Cancer Antigen (PSA) response rate per PCWG3 criteria	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%.	Every 4 weeks throughout study participation, up to 2 years
Secondary	Part 1: Time to PSA progression per PCWG3 criteria	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.	Every 4 weeks throughout study participation, up to 2 years
Secondary	Part 1: Duration of PSA response per PCWG3 criteria	Duration of PSA response is defined as the time from the date of first documented PSA response to the earliest date of PSA progression.	Every 4 weeks throughout study participation, up to 2 years
Secondary	Part 1: PSA percent change over time		Every 4 weeks throughout study participation, up to 2 years
Secondary	Part 1: Best PSA percent change		Every 4 weeks throughout study participation, up to 2 years
Secondary	Part 1: Time to first symptomatic skeletal event (SSE)	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.	Every 4 weeks throughout the study, up to 2 years
Secondary	Number of participants with adverse event (AEs), serious AEs (SAEs), and AEs leading to study treatment discontinuation.		Throughout the study, up to 2 years
Secondary	Number of participants who develop anti-drug antibodies		Throughout the study, up to 2 years
Secondary	Part 2: DoR per investigator assessment of RECIST 1.1 criteria	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.	Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years
Secondary	Part 2: Progression free survival (PFS) per investigator assessment of RECIST 1.1 criteria	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.	Every 8 weeks for the first 24 weeks, then every 12 weeks, up to 2 years