MGC018 With or Without MGA012 in Advanced Solid Tumors
- Conditions
- Metastatic Castrate Resistant Prostate CancerMelanomaNon Small Cell Lung CancerSquamous Cell Carcinoma of Head and NeckTriple Negative Breast CancerAdvanced Solid Tumor, Adult
- Interventions
- Biological: vobramitamab duocarmazine
- Registration Number
- NCT03729596
- Lead Sponsor
- MacroGenics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 143
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 5 vobramitamab duocarmazine 4.0 mg/kg IV every 3 weeks SCCHN expansion vobramitamab duocarmazine 3.0 mg/kg IV every 3 weeks Cohort 2 vobramitamab duocarmazine 1.0 mg/kg IV every 3 weeks Melanoma expansion vobramitamab duocarmazine 3.0 mg/kg IV every 3 weeks Cohort 1 vobramitamab duocarmazine 0.5 mg/kg IV every 3 weeks mCRPC expansion vobramitamab duocarmazine 3.0 mg/kg IV every 3 weeks Cohort 3 vobramitamab duocarmazine 2.0 mg/kg IV every 3 weeks Cohort 4 vobramitamab duocarmazine 3.0 mg/kg IV every 3 weeks NSCLC expansion vobramitamab duocarmazine 3.0 mg/kg IV every 3 weeks TNBC expansion vobramitamab duocarmazine 3.0 mg/kg IV every 3 weeks
- Primary Outcome Measures
Name Time Method Number of patients with Adverse Events of vobramitamab duocarmazine as assessed by CTCAE v4.03 Throughout the study up to 24 months 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.
Number of patients with dose limiting toxicities (DLT) up to 42 days from first dose Maximum tolerated or maximum administered dose of vobramitamab duocarmazine
- Secondary Outcome Measures
Name Time Method Best overall response (BOR) of vobramitamab duocarmazine Throughout the study for up to 24 months 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.
Objective response rate (ORR) of vobramitamab duocarmazine Efficacy evaluations every 9 weeks throughout the study for up to 24 months The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine
Progression free survival (PFS) of vobramitamab duocarmazine Every 9 weeks for up to 24 months 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.
Duration of response (DoR) of vobramitamab duocarmazine Throughout the study for up to 48 months 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.
Overall survival (OS) of vobramitamab duocarmazine Every 9 weeks for up to 24 months Efficacy assessed as the time from the first dose date to the date of death from any cause.
Tmax 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 Time to reach maximum (peak) plasma concentration of vobramitamab duocarmazine
PSA response rate Every 3 weeks up to 24 months Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later
Best PSA response Every 3 weeks up to 24 months For prostate cancer patients, the greatest change from baseline in PSA.
Area under the curve 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 plasma concentration versus time curve of vobramitamab duocarmazine
Cmax 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 Maximum Plasma Concentration of vobramitamab duocarmazine
Ctrough 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 Trough plasma concentration of vobramitamab duocarmazine
CL 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 Total body clearance of the drug from plasma of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
Vss 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 Apparent volume of distribution at steady state of vobramitamab duocarmazine
t1/2 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 . Terminal half life of vobramitamab duocarmazine
Immunogenicity Every 3 weeks through end of treatment, up to 24 months Percent of patients with anti-drug antibodies against vobramitamab duocarmazine
Trial Locations
- Locations (21)
The Johns Hopkins Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Virginia Cancer Specialist
🇺🇸Fairfax, Virginia, United States
UCLA Department of Medicine - Hematology/Oncology
🇺🇸Santa Monica, California, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz
🇵🇱Warsaw, Poland
Calvary Mater NewCastle
🇦🇺Waratah, Australia
St Vincent's Health Network (Kinghorn Cancer Centre)
🇦🇺Darlinghurst, Australia
The University of Queensland - Princess Alexandra Hospital (PAH)
🇦🇺Woolloongabba, Australia
Med-Polonia Sp. z o.o.
🇵🇱Poznań, Poland
Austin Health - Olivia Newton John Cancer Center
🇦🇺Heidelberg, Australia
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Ruber Internacional
🇪🇸Madrid, Spain
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii
🇵🇱Krakow, Poland
Carolina Biooncology Institute
🇺🇸Huntersville, North Carolina, United States
Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol
🇪🇸Barcelona, Spain
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii
🇵🇱Warszawa, Poland