Clinical trial NCT03729596: MGC018 With or Without MGA012 in Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Squamous Cell Carcinoma of Head and Neck
Triple Negative Breast Cancer
Melanoma
Advanced Solid Tumor, Adult
Metastatic Castrate Resistant Prostate Cancer
Non Small Cell Lung Cancer
Keywords: antibody-drug conjugate (ADC)
B7-H3
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2018-11-02
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with Adverse Events of vobramitamab duocarmazine as assessed by CTCAE v4.03
timeFrame: Throughout the study up to 24 months
measure: Number of patients with dose limiting toxicities (DLT)
timeFrame: up to 42 days from first dose
Secondary outcomes:
measure: Best overall response (BOR) of vobramitamab duocarmazine
timeFrame: Throughout the study for up to 24 months
measure: Objective response rate (ORR) of vobramitamab duocarmazine
timeFrame: Efficacy evaluations every 9 weeks throughout the study for up to 24 months
measure: Progression free survival (PFS) of vobramitamab duocarmazine
timeFrame: Every 9 weeks for up to 24 months
measure: Duration of response (DoR) of vobramitamab duocarmazine
timeFrame: Throughout the study for up to 48 months
measure: Overall survival (OS) of vobramitamab duocarmazine
timeFrame: Every 9 weeks for up to 24 months
measure: PSA response rate
timeFrame: Every 3 weeks up to 24 months
measure: Best PSA response
timeFrame: Every 3 weeks up to 24 months
measure: Area under the curve
timeFrame: 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
measure: Cmax
timeFrame: 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
measure: Tmax
timeFrame: 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
measure: Ctrough
timeFrame: 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
measure: CL
timeFrame: 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
measure: Vss
timeFrame: 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
measure: t1/2
timeFrame: 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 .
measure: Immunogenicity
timeFrame: Every 3 weeks through end of treatment, up to 24 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Department of Medicine - Hematology/Oncology
state: California
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: The Johns Hopkins Kimmel Cancer Center
state: Maryland
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Huntersville
country: United States
facility: Carolina Biooncology Institute
state: North Carolina
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialist
state: Virginia
city: Darlinghurst
country: Australia
facility: St Vincent's Health Network (Kinghorn Cancer Centre)
city: Heidelberg
country: Australia
facility: Austin Health - Olivia Newton John Cancer Center
city: Waratah
country: Australia
facility: Calvary Mater NewCastle
city: Woolloongabba
country: Australia
facility: The University of Queensland - Princess Alexandra Hospital (PAH)
city: Krakow
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii
city: Poznań
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz
city: Warszawa
country: Poland
facility: Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
Study officials:
affiliation: MacroGenics
name: Ashley Ward, M.D.
role: STUDY_DIRECTOR
References: