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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03729596




Registration number
NCT03729596
Ethics application status
Date submitted
30/10/2018
Date registered
2/11/2018

Titles & IDs
Public title
MGC018 With or Without MGA012 in Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
CP-MGC018-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Squamous Cell Carcinoma of Head and Neck 0 0
Triple Negative Breast Cancer 0 0
Melanoma 0 0
Advanced Solid Tumor, Adult 0 0
Metastatic Castrate Resistant Prostate Cancer 0 0
Non Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - vobramitamab duocarmazine

Experimental: Cohort 1 - 0.5 mg/kg IV every 3 weeks

Experimental: Cohort 2 - 1.0 mg/kg IV every 3 weeks

Experimental: Cohort 3 - 2.0 mg/kg IV every 3 weeks

Experimental: Cohort 4 - 3.0 mg/kg IV every 3 weeks

Experimental: Cohort 5 - 4.0 mg/kg IV every 3 weeks

Experimental: mCRPC expansion - 3.0 mg/kg IV every 3 weeks

Experimental: NSCLC expansion - 3.0 mg/kg IV every 3 weeks

Experimental: TNBC expansion - 3.0 mg/kg IV every 3 weeks

Experimental: Melanoma expansion - 3.0 mg/kg IV every 3 weeks

Experimental: SCCHN expansion - 3.0 mg/kg IV every 3 weeks


Treatment: Other: vobramitamab duocarmazine
Anti-B7H3 antibody drug conjugate

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of patients with Adverse Events of vobramitamab duocarmazine as assessed by CTCAE v4.03
Timepoint [1] 0 0
Throughout the study up to 24 months
Primary outcome [2] 0 0
Number of patients with dose limiting toxicities (DLT)
Timepoint [2] 0 0
up to 42 days from first dose
Secondary outcome [1] 0 0
Best overall response (BOR) of vobramitamab duocarmazine
Timepoint [1] 0 0
Throughout the study for up to 24 months
Secondary outcome [2] 0 0
Objective response rate (ORR) of vobramitamab duocarmazine
Timepoint [2] 0 0
Efficacy evaluations every 9 weeks throughout the study for up to 24 months
Secondary outcome [3] 0 0
Progression free survival (PFS) of vobramitamab duocarmazine
Timepoint [3] 0 0
Every 9 weeks for up to 24 months
Secondary outcome [4] 0 0
Duration of response (DoR) of vobramitamab duocarmazine
Timepoint [4] 0 0
Throughout the study for up to 48 months
Secondary outcome [5] 0 0
Overall survival (OS) of vobramitamab duocarmazine
Timepoint [5] 0 0
Every 9 weeks for up to 24 months
Secondary outcome [6] 0 0
PSA response rate
Timepoint [6] 0 0
Every 3 weeks up to 24 months
Secondary outcome [7] 0 0
Best PSA response
Timepoint [7] 0 0
Every 3 weeks up to 24 months
Secondary outcome [8] 0 0
Area under the curve
Timepoint [8] 0 0
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 outcome [9] 0 0
Cmax
Timepoint [9] 0 0
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 outcome [10] 0 0
Tmax
Timepoint [10] 0 0
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 outcome [11] 0 0
Ctrough
Timepoint [11] 0 0
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 outcome [12] 0 0
CL
Timepoint [12] 0 0
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 outcome [13] 0 0
Vss
Timepoint [13] 0 0
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 outcome [14] 0 0
t1/2
Timepoint [14] 0 0
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 outcome [15] 0 0
Immunogenicity
Timepoint [15] 0 0
Every 3 weeks through end of treatment, up to 24 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St Vincent's Health Network (Kinghorn Cancer Centre) - Darlinghurst
Recruitment hospital [2] 0 0
Austin Health - Olivia Newton John Cancer Center - Heidelberg
Recruitment hospital [3] 0 0
Calvary Mater NewCastle - Waratah
Recruitment hospital [4] 0 0
The University of Queensland - Princess Alexandra Hospital (PAH) - Woolloongabba
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
4105 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Poland
State/province [9] 0 0
Krakow
Country [10] 0 0
Poland
State/province [10] 0 0
Poznan
Country [11] 0 0
Poland
State/province [11] 0 0
Warsaw
Country [12] 0 0
Poland
State/province [12] 0 0
Warszawa
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MacroGenics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ashley Ward, M.D.
Address 0 0
MacroGenics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.