MGD009/MGA012 Combination in Relapsed/Refractory Cancer

NCT03406949 | Completed Phase 1 FDA Drug

• 1 other identifier: CP-MGD009-02
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of obrindatamab administered in combination with retifanlimab in patients with B7-H3- expressing tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events 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.

  30 months

• MTD/MAD

  Maximum Tolerated or Administrated Dose of obrindatamab and retifanlimab

  18 months

Secondary Outcomes (9)

• AUC

  30 months

• Cmax

  30 months

• Tmax

  30 months

• Ctrough

  30 months

• CL

  30 months

Study Arms (1)

obrindatamab + retifanlimab

EXPERIMENTAL

B7-H3 x CD3 DART protein + anti-PD-1 antibody

Biological: obrindatamab; Biological: retifanlimab

Interventions

obrindatamab BIOLOGICAL

B7-H3 x CD3 DART protein

Also known as: MGD009

obrindatamab + retifanlimab

retifanlimab BIOLOGICAL

anti-PD-1 antibody

Also known as: INCMGA00012, MGA012

obrindatamab + retifanlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-proven, unresectable locally advanced or metastatic solid tumors of any histology that test positive for B7-H3 expression on tumor cells or vasculature for whom no approved therapy with demonstrated clinical benefit is available. For all tumor types, the requirement for previous systemic therapy may be waived if a patient was intolerant of or refused standard first-line therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Measurable disease, with the exception of prostate cancer
• Tissue specimen available for B7-H3 and PD-L1 expression testing
• Acceptable laboratory parameters
• Patients who have previously received an immune checkpoint inhibitor (e.g., anti- PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have toxicities related to the checkpoint inhibitor resolved to ≤ Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous hypothyroidism toxicity on a checkpoint inhibitor are eligible to enter study regardless of Grade resolution as long as the patient is well controlled on thyroid replacement hormones.

You may not qualify if:

• Patients with history of prior central nervous system (CNS) metastasis must have been treated, must be asymptomatic, and must not have any of the following at the time of enrollment:
• No concurrent treatment for the CNS disease (e.g. surgery, radiation, corticosteroids \>10 mg prednisone/day or equivalent)
• No progression of CNS metastases on MRI or CT for at least 14 days after last day of prior therapy for the CNS metastases
• No concurrent leptomeningeal disease or cord compression
• Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing
• Treatment with any, investigational therapy within the 4 weeks prior to the initiation of study drug administration
• Treatment with any systemic chemotherapy within 3 weeks
• Treatment with radiation therapy within 2 weeks
• History of allogeneic bone marrow, stem-cell, or solid organ transplant
• Treatment with systemic corticosteroids (\> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within 2 weeks
• Clinically significant cardiovascular or pulmonary disease
• Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Patients requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than one week prior to the initiation of study drug.
• Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome
• Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction

Sponsors & Collaborators

• MacroGenics: lead

Study Sites (10)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

START (South Texas Accelerated Research Therapeutics) - Midwest

Grand Rapids, Michigan, 49546, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Center

Dallas, Texas, 75251, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Study Officials

• Stephen L Eck, M.D.

  MacroGenics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3+3 dose escalation design followed by Cohort Expansion Phase.

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: January 23, 2018
• Study Start: February 27, 2018
• Primary Completion: April 27, 2022
• Study Completion: April 27, 2022
• Last Updated: May 19, 2022

Record last verified: 2022-05

Locations

US (10)