MGD009/MGA012 Combination in Relapsed/Refractory Cancer

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03406949
• Other study ID #: CP-MGD009-02
• Status: Completed
• Phase: Phase 1
• Start date: February 27, 2018
• Est. completion date: April 27, 2022

Study information

• Verified date: May 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 and tolerability, pharmacokinetics (PK) pharmacodynamics and preliminary antitumor activity of obrindatamab administered in combination with retifanlimab in patients with B7-H3- expressing tumors.

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 obrindatamab and retifanlimab, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 27, 2022
• Est. primary completion date: April 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Biological:
• obrindatamab
B7-H3 x CD3 DART protein
• retifanlimab
anti-PD-1 antibody

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mary Crowley Cancer Center	Dallas	Texas
United States	City of Hope Medical Center	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	START (South Texas Accelerated Research Therapeutics) - Midwest	Grand Rapids	Michigan
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Southern California	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
MacroGenics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	MTD/MAD	Maximum Tolerated or Administrated Dose of obrindatamab and retifanlimab	18 months
Secondary	AUC	Area Under the Plasma Concentration versus Time Curve of obrindatamab and retifanlimab	30 months
Secondary	Cmax	Maximum Plasma Concentration of obrindatamab and retifanlimab	30 months
Secondary	Tmax	Time to reach maximum (peak) plasma concentration of obrindatamab and retifanlimab	30 months
Secondary	Ctrough	Trough plasma concentration of obrindatamab and retifanlimab	30 months
Secondary	CL	Total body clearance of the drug from plasma of obrindatamab and retifanlimab	30 months
Secondary	Vss	Apparent volume of distribution at steady state of obrindatamab and retifanlimab	30 months
Secondary	t1/2	Terminal half life of obrindatamab and retifanlimab	30 months
Secondary	ADA	Percent of patients with anti-drug antibody to obrindatamab and retifanlimab	30 months
Secondary	Anti-tumor activity	Conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related response criteria (irRECIST)	30 months