MGC018 With or Without MGA012 in Advanced Solid Tumors

A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of MGC018 (Anti-B7-H3 Antibody Drug Conjugate) Alone and in Combination With MGA012 (Anti-PD-1 Antibody) in Patients With Advanced Solid Tumors

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of vobramitamab duocarmazine (MGC018) in patients with advanced solid tumors. Patients with solid tumors will be enrolled in the Dose Escalation Phase; Cohort Expansion will include metastatic castrate-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Patients who do not experience unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles for up to two years. Patients in Cohort Expansion will be followed for survival every 3 months for 2 years following last dose.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Non Small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Cancer; Metastatic Castrate Resistant Prostate Cancer; Advanced Solid Tumor, Adult
• Intervention / Treatment: Biological: vobramitamab duocarmazine

Detailed Description

This Phase 1/2 study will characterize safety, dose-limiting toxicities (DLTs), and maximum tolerated/administered dose (MTD/MAD) and anti-tumor activity for vobramitamab duocarmazine as monotherapy (Module A) in patients with advanced solid tumors. Patients with solid tumors will be enrolled in the Dose Escalation Phase; Cohort Expansion will include metastatic castrate-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma. Patients who do not experience unacceptable toxicity or meet criteria for permanent discontinuation may undergo additional cycles for up to two years. Patients in Cohort Expansion will be followed for survival every 3 months for 2 years following last dose.

Module B, vobramitamab duocarmazine in combination with retifanlimab will not enroll.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst, Australia, 2010
    • St Vincent's Health Network (Kinghorn Cancer Centre)
  • Heidelberg, Australia, 3084
    • Austin Health - Olivia Newton John Cancer Center
  • Waratah, Australia, 2298
    • Calvary Mater Newcastle
  • Woolloongabba, Australia, 4105
    • The University of Queensland - Princess Alexandra Hospital (PAH)
• Poland
  • Krakow, Poland, 31-501
    • Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii
  • Poznań, Poland, 60-693
    • Med-Polonia Sp. z o.o.
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz
  • Warszawa, Poland, 01-748
    • Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain
    • Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol
  • Madrid, Spain, 28034
    • Hospital Ruber Internacional
  • Madrid, Spain, 20850
    • Hospital Universitario HM Sanchinarro
• United States
  • California
    • Santa Monica, California, United States, 90404
      • UCLA Department of Medicine - Hematology/Oncology
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • The Johns Hopkins Kimmel Cancer Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression.
• Eastern Cooperative Oncology Group performance status of ≤2
• Life expectancy ≥ 12 weeks for dose escalation phase and ≥ 24 weeks for cohort expansion phase
• Measurable disease. Prostate cancer patients with bone only disease are eligible.
• Acceptable laboratory parameters and adequate organ reserve.
• Dose Escalation Phase: Patients with histologically proven, unresectable, locally advanced or metastatic solid tumors for whom no therapy with demonstrated clinical benefit is available.

Module A Cohort Expansion:

• mCRPC that has progressed with one prior line of chemotherapy for metastatic disease and no more than two prior lines of anti-hormonal therapy.
• NSCLC: metastatic disease after standard cytotoxic, targeted, and biologic or checkpoint inhibitor therapy. No more than 2 prior lines of chemotherapy.
• TNBC: Locally advance or metastatic disease that has progressed following at least one systemic therapy.
• SCCHN that has progressed during or following at least one systemic therapy for metastatic or recurrent unresectable disease. No more than 2 prior lines of chemotherapy.
• Melanoma that has progressed during or following at least one systemic treatment for unresectable locally advanced or metastatic disease. Patients who are intolerant of or refused standard therapy are eligible.

Exclusion Criteria:

• Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on MRI, CT or PET within 6 months, or history of leptomeningeal disease or cord compression at the time of enrollment.
• Prior treatment with B7-H3 targeted agents for cancer.
• Treatment with systemic cancer therapy, biologic agents, or anti-hormonal therapy (mCRPC) within 4 weeks, prior small molecule targeted or kinase inhibitors within 14 days or 5 half-lives, prior radioligand within 6 months
• Clinically significant cardiovascular disease.
• Clinically significant pulmonary compromise or requirement for supplemental oxygen.
• History of clinically-significant cardiovascular disease, including but not limited to pericarditis or pericardial effusion.
• Active viral (including confirmed or presumed COVID-19), bacterial, or systemic fungal infection requiring parenteral treatment within 7 days of first study drug administration.
• Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction.
• Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
• Major trauma or major surgery within 4 weeks of first study drug administration.
• Clinically significant venous insufficiency.
• > Grade 1 peripheral neuropathy.
• Evidence of pleural effusion.
• Evidence of ascites.
• Serum testosterone >50 ng/dl or >1.7 nmol/L in mCRPC in Module A Cohort Expansion Phase

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 0.5 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: Cohort 2; 1.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: Cohort 3; 2.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: Cohort 4; 3.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: Cohort 5; 4.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: mCRPC expansion; 3.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: NSCLC expansion; 3.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: TNBC expansion; 3.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: Melanoma expansion; 3.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018
Experimental: SCCHN expansion; 3.0 mg/kg IV every 3 weeks	Biological: vobramitamab duocarmazine; Anti-B7H3 antibody drug conjugate; Other Names: MGC018

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with Adverse Events of vobramitamab duocarmazine as assessed by CTCAE v4.03	Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.	Throughout the study up to 24 months
Number of patients with dose limiting toxicities (DLT)	Maximum tolerated or maximum administered dose of vobramitamab duocarmazine	up to 42 days from first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response (BOR) of vobramitamab duocarmazine	The best response recorded from the start of the study treatment until the end of treatment with vobramitamab duocarmazine, taking into account any requirement for confirmation of response.	Throughout the study for up to 24 months
Objective response rate (ORR) of vobramitamab duocarmazine	The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine	Efficacy evaluations every 9 weeks throughout the study for up to 24 months
Progression free survival (PFS) of vobramitamab duocarmazine	Efficacy assessed as the first dose date to the date of first documented progression using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first.	Every 9 weeks for up to 24 months
Duration of response (DoR) of vobramitamab duocarmazine	Efficacy assessed as the time from the date of initial objective response to the date of first documented progression RECIST v1.1, or the date of death from any cause, whichever occurs first.	Throughout the study for up to 48 months
Overall survival (OS) of vobramitamab duocarmazine	Efficacy assessed as the time from the first dose date to the date of death from any cause.	Every 9 weeks for up to 24 months
PSA response rate	Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later	Every 3 weeks up to 24 months
Best PSA response	For prostate cancer patients, the greatest change from baseline in PSA.	Every 3 weeks up to 24 months
CL	Total body clearance of the drug from plasma of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab	Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months
Area under the curve	Area under the plasma concentration versus time curve of vobramitamab duocarmazine	Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months
Cmax	Maximum Plasma Concentration of vobramitamab duocarmazine	Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months
Tmax	Time to reach maximum (peak) plasma concentration of vobramitamab duocarmazine	Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months
Ctrough	Trough plasma concentration of vobramitamab duocarmazine	Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months
Vss	Apparent volume of distribution at steady state of vobramitamab duocarmazine	Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months
t1/2	Terminal half life of vobramitamab duocarmazine	Cycle 1 (each cycle is 21 days) and Cycle 2: Predose, end of infusion (EOI), 1, 4, 24, 72 hours post-infusion and predose on Days 8, 15 and 22; Predose and EOI samples collected at Day 1 Cycle 3 and afterwards for up to 24 months .
Immunogenicity	Percent of patients with anti-drug antibodies against vobramitamab duocarmazine	Every 3 weeks through end of treatment, up to 24 months

Collaborators and Investigators

• Sponsor: MacroGenics
• Investigators: Study Director: Ashley Ward, M.D., MacroGenics

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2018
• Primary Completion (Actual): March 18, 2023
• Study Completion (Actual): March 18, 2023

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: B7-H3; antibody-drug conjugate (ADC)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms
• Other Study ID Numbers: CP-MGC018-01

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