MGC018 With or Without MGA012 in Advanced Solid Tumors
Primary Purpose
Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Cancer, Melanoma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
vobramitamab duocarmazine
Sponsored by
![MacroGenics](https://trials-media.s3.amazonaws.com/orgs/macrogenics.jpeg)
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of Head and Neck focused on measuring antibody-drug conjugate (ADC), B7-H3
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
Sites / Locations
- UCLA Department of Medicine - Hematology/Oncology
- Sibley Memorial Hospital
- The Johns Hopkins Kimmel Cancer Center
- START Midwest
- Nebraska Methodist Hospital
- Comprehensive Cancer Centers of Nevada
- Carolina Biooncology Institute
- Inova Schar Cancer Institute
- Virginia Cancer Specialist
- St Vincent's Health Network (Kinghorn Cancer Centre)
- Austin Health - Olivia Newton John Cancer Center
- Calvary Mater NewCastle
- The University of Queensland - Princess Alexandra Hospital (PAH)
- Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii
- Med-Polonia Sp. z o.o.
- Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz
- Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii
- Hospital Universitario Vall d'Hebron
- Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol
- Hospital Universitario HM Sanchinarro
- Hospital Ruber Internacional
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
mCRPC expansion
NSCLC expansion
TNBC expansion
Melanoma expansion
SCCHN expansion
Arm Description
0.5 mg/kg IV every 3 weeks
1.0 mg/kg IV every 3 weeks
2.0 mg/kg IV every 3 weeks
3.0 mg/kg IV every 3 weeks
4.0 mg/kg IV every 3 weeks
3.0 mg/kg IV every 3 weeks
3.0 mg/kg IV every 3 weeks
3.0 mg/kg IV every 3 weeks
3.0 mg/kg IV every 3 weeks
3.0 mg/kg IV every 3 weeks
Outcomes
Primary Outcome Measures
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.
Number of patients with dose limiting toxicities (DLT)
Maximum tolerated or maximum administered dose of vobramitamab duocarmazine
Secondary Outcome Measures
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.
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
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.
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.
Overall survival (OS) of vobramitamab duocarmazine
Efficacy assessed as the time from the first dose date to the date of death from any cause.
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
Best PSA response
For prostate cancer patients, the greatest change from baseline in PSA.
Area under the curve
Area under the plasma concentration versus time curve of vobramitamab duocarmazine
Cmax
Maximum Plasma Concentration of vobramitamab duocarmazine
Tmax
Time to reach maximum (peak) plasma concentration of vobramitamab duocarmazine
Ctrough
Trough plasma concentration of vobramitamab duocarmazine
CL
Total body clearance of the drug from plasma of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
Vss
Apparent volume of distribution at steady state of vobramitamab duocarmazine
t1/2
Terminal half life of vobramitamab duocarmazine
Immunogenicity
Percent of patients with anti-drug antibodies against vobramitamab duocarmazine
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03729596
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Business decision
Study Start Date
November 21, 2018 (Actual)
Primary Completion Date
March 18, 2023 (Actual)
Study Completion Date
March 18, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MacroGenics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Dose escalation will use a 3+3+3 design to identify an MAD or MTD, followed by a Cohort Expansion.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
143 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
0.5 mg/kg IV every 3 weeks
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
1.0 mg/kg IV every 3 weeks
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
2.0 mg/kg IV every 3 weeks
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
3.0 mg/kg IV every 3 weeks
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
4.0 mg/kg IV every 3 weeks
Arm Title
mCRPC expansion
Arm Type
Experimental
Arm Description
3.0 mg/kg IV every 3 weeks
Arm Title
NSCLC expansion
Arm Type
Experimental
Arm Description
3.0 mg/kg IV every 3 weeks
Arm Title
TNBC expansion
Arm Type
Experimental
Arm Description
3.0 mg/kg IV every 3 weeks
Arm Title
Melanoma expansion
Arm Type
Experimental
Arm Description
3.0 mg/kg IV every 3 weeks
Arm Title
SCCHN expansion
Arm Type
Experimental
Arm Description
3.0 mg/kg IV every 3 weeks
Intervention Type
Biological
Intervention Name(s)
vobramitamab duocarmazine
Other Intervention Name(s)
MGC018
Intervention Description
Anti-B7H3 antibody drug conjugate
Primary Outcome Measure Information:
Title
Number of patients with Adverse Events of vobramitamab duocarmazine as assessed by CTCAE v4.03
Description
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.
Time Frame
Throughout the study up to 24 months
Title
Number of patients with dose limiting toxicities (DLT)
Description
Maximum tolerated or maximum administered dose of vobramitamab duocarmazine
Time Frame
up to 42 days from first dose
Secondary Outcome Measure Information:
Title
Best overall response (BOR) of vobramitamab duocarmazine
Description
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.
Time Frame
Throughout the study for up to 24 months
Title
Objective response rate (ORR) of vobramitamab duocarmazine
Description
The percentage of participants who achieve a complete response (CR or partial response (PR) to treatment with vobramitamab duocarmazine
Time Frame
Efficacy evaluations every 9 weeks throughout the study for up to 24 months
Title
Progression free survival (PFS) of vobramitamab duocarmazine
Description
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.
Time Frame
Every 9 weeks for up to 24 months
Title
Duration of response (DoR) of vobramitamab duocarmazine
Description
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.
Time Frame
Throughout the study for up to 48 months
Title
Overall survival (OS) of vobramitamab duocarmazine
Description
Efficacy assessed as the time from the first dose date to the date of death from any cause.
Time Frame
Every 9 weeks for up to 24 months
Title
PSA response rate
Description
Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA) with confirmation at least 3 weeks later
Time Frame
Every 3 weeks up to 24 months
Title
Best PSA response
Description
For prostate cancer patients, the greatest change from baseline in PSA.
Time Frame
Every 3 weeks up to 24 months
Title
Area under the curve
Description
Area under the plasma concentration versus time curve of vobramitamab duocarmazine
Time Frame
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
Title
Cmax
Description
Maximum Plasma Concentration of vobramitamab duocarmazine
Time Frame
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
Title
Tmax
Description
Time to reach maximum (peak) plasma concentration of vobramitamab duocarmazine
Time Frame
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
Title
Ctrough
Description
Trough plasma concentration of vobramitamab duocarmazine
Time Frame
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
Title
CL
Description
Total body clearance of the drug from plasma of vobramitamab duocarmazine and vobramitamab duocarmazine+retifanlimab
Time Frame
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
Title
Vss
Description
Apparent volume of distribution at steady state of vobramitamab duocarmazine
Time Frame
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
Title
t1/2
Description
Terminal half life of vobramitamab duocarmazine
Time Frame
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 .
Title
Immunogenicity
Description
Percent of patients with anti-drug antibodies against vobramitamab duocarmazine
Time Frame
Every 3 weeks through end of treatment, up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashley Ward, M.D.
Organizational Affiliation
MacroGenics
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Department of Medicine - Hematology/Oncology
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Sibley Memorial Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20016
Country
United States
Facility Name
The Johns Hopkins Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
START Midwest
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49546
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Carolina Biooncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Inova Schar Cancer Institute
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Virginia Cancer Specialist
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
St Vincent's Health Network (Kinghorn Cancer Centre)
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
Facility Name
Austin Health - Olivia Newton John Cancer Center
City
Heidelberg
ZIP/Postal Code
3084
Country
Australia
Facility Name
Calvary Mater NewCastle
City
Waratah
ZIP/Postal Code
2298
Country
Australia
Facility Name
The University of Queensland - Princess Alexandra Hospital (PAH)
City
Woolloongabba
ZIP/Postal Code
4105
Country
Australia
Facility Name
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie Oddział Kliniczny Onkologii
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
Facility Name
Med-Polonia Sp. z o.o.
City
Poznań
ZIP/Postal Code
60-693
Country
Poland
Facility Name
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Oddział Badań Wczesnych Faz
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Magodent Sp. z o.o. Szpital Elbląska Oddział Onkologii Klinicznej/ Chemioterapii
City
Warszawa
ZIP/Postal Code
01-748
Country
Poland
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Institut Català D'Oncologia - Hospital Universitari Germans Trias I Pujol
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario HM Sanchinarro
City
Madrid
ZIP/Postal Code
20850
Country
Spain
Facility Name
Hospital Ruber Internacional
City
Madrid
ZIP/Postal Code
28034
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
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MGC018 With or Without MGA012 in Advanced Solid Tumors
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