Safety Study of MGD009 in B7-H3-expressing Tumors

Breast Cancer Clinical Trial

Official title:

Phase 1, First-in-Human, Open Label, Dose Escalation Study of MGD009, A Humanized B7-H3 x CD3 Dual-Affinity Re-Targeting (DART) Protein in Patients With Unresectable or Metastatic B7-H3-Expressing Neoplasms

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02628535
• Other study ID #: CP-MGD009-01
• Status: Terminated
• Phase: Phase 1
• Start date: September 2015
• Est. completion date: November 25, 2019

Study information

• Verified date: February 2022
• 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 of MGD009 when given to patients with B7-H3-expressing tumors. The study will also evaluate what is the highest dose of MGD009 that can be given safely. Assessments will be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics (PD) and to evaluate potential anti-tumor activity of MGD009.

Description:

This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy follow-up study of MGD009 administered intravenously (IV) on an every-other-week schedule for up to one year (14 cycles).

The dose escalation phase is designed to characterize the safety and tolerability of MGD009 and to define the maximum tolerated or maximum administered dose (MTD/MAD). This phase will enroll patients with mesothelioma, bladder cancer, melanoma, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), ovarian cancer, thyroid cancer, triple-negative breast cancer (TNBC), pancreatic cancer, colon cancer, soft tissue sarcoma, or prostate cancer.

In the cohort expansion phase, 6 cohorts of 16 patients each will be enrolled to further evaluate the safety and potential efficacy of MGD009 administered at the MTD/MAD dose in patients with mesothelioma, bladder cancer, melanoma, SCCHN, NSCLC, or other specific tumors that express high levels of B7-H3. Pre- and on-study biopsies are required for melanoma patients in the cohort expansion phase. Two additional cohorts (up to15 patients each) will evaluate the use of prophylaxis therapies to mitigate toxicity.

The survival follow-up phase consists of the 2-year period after the final dose of study drug.

All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 67
• Est. completion date: November 25, 2019
• Est. primary completion date: November 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically and/or cytologically proven unresectable locally advanced or metastatic tumors that express B7-H3 on the membrane or vasculature. The requirement for previous systemic therapy may be waived if a person was intolerant of standard front-line therapy

• Dose escalation phase prior systemic treatment requirements:

• pleural mesothelioma, pancreatic cancer: 1-3 prior treatments

• urothelial, SCHNN, prostate, soft tissue sarcoma, prostate cancer, TNBC, ccRCC, NSCLC:

1-5 prior treatments

• ovarian cancer: 2-4 prior treatments

• colon cancer: 2-4 prior treatments

• cutaneous melanoma: at least 1 prior treatment (including immunotherapy).

• Patients with prior immune checkpoint inhibitors must have related toxicities reduced to Grade 0, 1, or baseline

• Measurable disease per RECIST 1.1 criteria

• Easter Cooperative Oncology Group (ECOG) performance status 0 or 1

• Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria:

• Patients with central nervous system (CNS) involvement must have been treated, be asymptomatic, do not exhibit progression of CNS metastases on MRI or CT within 28 days, and do not have concurrent leptomeningeal disease or cord compression.

• Clinically significant pulmonary compromise within 28 days of first dose, including pneumonia, pneumonitis, requirement for supplemental oxygen). use to maintain adequate oxygenation, or pleural effusion sufficient to warrant pleurocentesis or any history of = Grade 3 drug induced or radiation pneumonitis.

• History of autoimmune disease with certain exceptions such as vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic therapy within the past 2 years, patients with history of Hashimoto's or Grave's disease that are now euthyroid clinically and by lab testing

• History of clinically-significant cardiovascular disease, or cardiac arrhythmias, including atrial fibrillation at screening or day of treatment

• History of clinically-significant gastrointestinal (GI) disease; GI perforation within 1 year; GI bleeding or acute pancreatitis within 3 months; or diverticulitis within 4 weeks of first study drug administration

• Active viral, 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 (PCR)

• Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome

• History of allogeneic bone marrow, stem cell, or solid organ transplant

• Treatment with systemic cancer therapy or investigational therapy within 3 weeks of first study drug administration; radiation within 2 weeks; corticosteroids (greater than or equal to 10 mg prednisone or equivalent per day) or other immune suppressive drugs within 2 weeks of first study drug administration

• Trauma or major surgery within 4 weeks of first study drug administration

• Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGD009

Related Conditions & MeSH terms

• Bladder Cancer
• Breast Cancer
• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Colon Cancer
• Melanoma
• Mesothelioma
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Prostate Cancer
• Sarcoma
• Soft Tissue Sarcoma
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Thyroid Cancer

Intervention

Biological:
• MGD009
B7-H3 x CD3 DART protein

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Saint Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	UCLA	Los Angeles	California
United States	Henry-Joyce Cancer Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	New York University	New York	New York
United States	Stanford University School of Medicine	Palo Alto	California
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	University of California - San Francisco	San Francisco	California
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	adverse events, serious adverse events	28 days after last dose of study drug
Secondary	Peak plasma concentration	PK of MGD009	8 days
Secondary	Number of participants that develop anti-drug antibodies	Proportion of patients who develop anti-MGD0009 antibodies, immunogenicity	first dose through 28 days after last dose of study drug
Secondary	Change in tumor volume	Anti-tumor activity of MGD009 using both conventional RECIST 1.1 and immune-related RECIST criteria.	Weeks 6, 15, 24, 33, 42, 51, 60, 69, 78, 87, 96, 105