MGC018 With or Without MGA012 in Advanced Solid Tumors

Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03729596
• Other study ID #: CP-MGC018-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 21, 2018
• Est. completion date: March 18, 2023

Study information

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

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 143
• Est. completion date: March 18, 2023
• Est. primary completion date: March 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor, Adult
• Melanoma
• Metastatic Castrate Resistant Prostate Cancer
• Non Small Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate

Locations

Country	Name	City	State
Australia	St Vincent's Health Network (Kinghorn Cancer Centre)	Darlinghurst
Australia	Austin Health - Olivia Newton John Cancer Center	Heidelberg
Australia	Calvary Mater NewCastle	Waratah
Australia	The University of Queensland - Princess Alexandra Hospital (PAH)	Woolloongabba
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Onkologii	Krakow
Poland	Med-Polonia Sp. z o.o.	Poznan
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Oddzial Badan Wczesnych Faz	Warsaw
Poland	Magodent Sp. z o.o. Szpital Elblaska Oddzial Onkologii Klinicznej/ Chemioterapii	Warszawa
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol	Barcelona
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
United States	The Johns Hopkins Kimmel Cancer Center	Baltimore	Maryland
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Virginia Cancer Specialist	Fairfax	Virginia
United States	START Midwest	Grand Rapids	Michigan
United States	Carolina Biooncology Institute	Huntersville	North Carolina
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UCLA Department of Medicine - Hematology/Oncology	Santa Monica	California
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Countries where clinical trial is conducted

United States,  Australia,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Best PSA response	For prostate cancer patients, the greatest change from baseline in PSA.	Every 3 weeks up to 24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 .
Secondary	Immunogenicity	Percent of patients with anti-drug antibodies against vobramitamab duocarmazine	Every 3 weeks through end of treatment, up to 24 months