This study is a Phase 1 open-label, dose escalation, cohort expansion, and efficacy
follow-up study of MGA271 administered intravenously (IV) on a weekly schedule for up to 51
doses in combination with IV pembrolizumab administered on an every-3-week schedule for up
to 17 doses.
The dose escalation phase is designed to characterize the safety and tolerability of the
combination of MGA271 and pembrolizumab and to define the maximum tolerated or maximum
administered dose (MTD/MAD). Only patients with melanoma will be enrolled in this study
In the cohort expansion phase, 3 cohorts of 16 patients each will be enrolled to further
evaluate the safety and potential efficacy of the combination administered at the MTD/MAD
dose in patients with melanoma, NSCLC, and SCCHN. Pre- and on-study biopsies are required
for melanoma patients in the cohort expansion phase.
The efficacy follow-up period consists of the 2-year period after the final dose of study
All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid
Tumors (RECIST) and immune-related response criteria (irRC).
- Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN,
or squamous cell NSCLC that express B7-H3.
- Melanoma that has progressed during or following at least 1 and up to 5 prior
systemic treatments for unresectable locally advanced or metastatic disease, or
melanoma patients who are intolerable of or have refused standard first line cancer
therapy. Pre- and on-study biopsy required.
- SCCHN that has progressed during or following at least 1 and up to 5 prior systemic
treatments for metastatic or recurrent disease deemed to be incurable. Patient who
refuse radical resection for recurrent disease or are intolerant of or refused
standard first line therapy are eligible to enroll
- Squamous cell NSCLC that has progressed during or following 1 - 5 prior systemic
therapies for unresectable locally advanced or metastatic disease (at least one
docetaxel, gemcitabine, or platinum analogue based therapy), or are intolerant of or
refused standard first line cancer therapy.
- Measurable disease per RECIST 1.1 criteria
- Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
- Acceptable laboratory parameters and adequate organ reserve.
- Patients with a history of symptomatic central nervous system metastases, unless
treated and asymptomatic
- Patients with history of autoimmune disease with certain exceptions such as vitiligo,
resolved chilhood atopic dermatitis, psoriasis not requiring systemic therapy within
the past 2 years, patients with history of Grave's disease that are now euthyroid
clinically and by lab testing
- History of allogeneic bone marrow, stem cell, or solid organ transplant
- Treatment with systemic cancer therapy or investigational therapy within 4 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
- History of clinically-significant cardiovascular disease; gastrointestinal
perforation; gastrointestinal bleeding, acute pancreatitis 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
- Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient
contained in the drug or vehicle formulation for MGA271 or pembrolizumab.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both