MGD009/MGA012 Combination in Relapsed/Refractory Cancer

• ClinicalTrials.gov Identifier: NCT03406949
• Recruitment Status: Active, not recruiting
• First Posted: January 23, 2018
• Last Update Posted: August 21, 2020
• Sponsor: MacroGenics
• Information provided by (Responsible Party): MacroGenics

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of MGD009 administered in combination with MGA012 in patients with B7-H3- expressing tumors.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Biological: MGD009; Biological: MGA012	Phase 1

Detailed Description:

This study is a Phase 1, open-label, dose escalation, and cohort expansion study designed to characterize the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary antitumor activity of the combination of MGD009 and MGA012, each of which is administered by IV infusion.The study consists of a Dose Escalation Phase to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) (if no MTD is defined) of the combination, followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of the combination with the doses established in the Dose Escalation Phase. Patients with B7-H3-expressing unresectable, locally advanced, or metastatic solid tumors of any histology will be enrolled in the Dose Escalation Phase. Following the establishment of an MTD, additional patients with specific tumor types will enroll in the Cohort Expansion Phase.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: 3+3+3 dose escalation design followed by Cohort Expansion Phase.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open Label, Dose Escalation Study of MGD009, a Humanized B7-H3 x CD3 DART® Protein, in Combination With MGA012, an Anti-PD-1 Antibody, in Patients With Relapsed or Refractory B7-H3-Expressing Tumors
• Actual Study Start Date: February 27, 2018
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: MGD009 + MGA012; B7-H3 x CD3 DART protein + anti-PD-1 antibody	Biological: MGD009; B7-H3 x CD3 DART protein; Other Name: orlotamab; Biological: MGA012; anti-PD-1 antibody; Other Name: INCMGA00012

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 [ Time Frame: 30 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.
2. MTD/MAD [ Time Frame: 18 months ]
   Maximum Tolerated or Administrated Dose of MGD009 and MGA012

Secondary Outcome Measures :

1. AUC [ Time Frame: 30 months ]
   Area Under the Plasma Concentration versus Time Curve of MGD009 and MGA012
2. Cmax [ Time Frame: 30 months ]
   Maximum Plasma Concentration of MGD009 and MGA012
3. Tmax [ Time Frame: 30 months ]
   Time to reach maximum (peak) plasma concentration of MGD009 and MGA012
4. Ctrough [ Time Frame: 30 months ]
   Trough plasma concentration of MGD009 and MGA012
5. CL [ Time Frame: 30 months ]
   Total body clearance of the drug from plasma of MGD009 and MGA012
6. Vss [ Time Frame: 30 months ]
   Apparent volume of distribution at steady state of MGD009 and MGA012
7. t1/2 [ Time Frame: 30 months ]
   Terminal half life of MGD009 and MGA012
8. ADA [ Time Frame: 30 months ]
   Percent of patients with anti-drug antibody to MGD009 and MGA012
9. Anti-tumor activity [ Time Frame: 30 months ]
   Conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related response criteria (irRECIST)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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:

  1. No concurrent treatment for the CNS disease (e.g. surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent)
  2. No progression of CNS metastases on MRI or CT for at least 14 days after last day of prior therapy for the CNS metastases
  3. 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

Contacts and Locations

Locations

United States, California

City of Hope Medical Center

Duarte, California, United States, 91010

University of Southern California

Los Angeles, California, United States, 90033

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02214

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

START (South Texas Accelerated Research Therapeutics) - Midwest

Grand Rapids, Michigan, United States, 49546

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

Mary Crowley Cancer Center

Dallas, Texas, United States, 75251

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

Sponsors and Collaborators

MacroGenics

Investigators

• Study Director: Stacie Goldberg, MD; MacroGenics

More Information

• Responsible Party: MacroGenics
• ClinicalTrials.gov Identifier: NCT03406949
• Other Study ID Numbers: CP-MGD009-02
• First Posted: January 23, 2018
• Last Update Posted: August 21, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No