The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics (PK)
pharmacodynamics and preliminary antitumor activity of MGC018 administered alone and in
combination with MGA012 in patients with advanced solid tumors.
This Phase 1/2, bifurcated-design study will characterize safety, dose-limiting toxicities
(DLTs), and maximum tolerated/administered dose (MTD/MAD) for MGC018 as monotherapy (Module
A) or in combination with MGA012 (Module B) in patients with advanced solid tumors. Module B
will commence after the MTD/MAD of MGC018 monotherapy is defined. Each module consists of a
Dose Escalation (3+3+3 design) followed by a Cohort Expansion Phase. Patients with solid
tumors of any histology will be enrolled in the Dose Escalation Phases; Cohort Expansion will
include disease-specific cohorts. Patients who do not experience DLT/unacceptable toxicity or
meet criteria for permanent discontinuation may undergo additional cycles. Patients will be
followed for survival every 3 months for 2 years following last dose.
- Tissue specimen available for retrospective analysis of B7-H3 and PD-L1 expression.
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Life expectancy ≥ 12 weeks
- Measurable disease
- Dose Escalation Phase: Patients with histologically proven, unresectable, locally
advanced or metastatic solid tumors 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
- Cohort Expansion Phase: Disease-specific prior therapy requirements to be specified.
- Acceptable laboratory parameters and adequate organ reserve.
- Patients with prior immune checkpoint inhibitors must have related toxicities reduced
to Grade 0, 1, or baseline, with the exception of well-controlled hypothyroidism.
- Patients with history of prior central nervous system (CNS) metastasis must have been
treated, be asymptomatic, and not have concurrent treatment for CNS disease,
progression of CNS metastases on MRI or CT for at least 21 days after last day of
prior therapy for the CNS metastases, or concurrent leptomeningeal disease or cord
compression at the time of enrollment.
- 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 Grave's disease that are now euthyroid clinically
and by lab testing.
- Patients who experienced the following immune checkpoint inhibitor-related AEs make
the patient ineligible despite the AE resolving to ≤ Grade 1 or baseline: ≥ Grade 3
ocular AE, neurologic toxicity, colitis, pneumonitis, renal toxicity; changes in liver
function tests that met criteria for Hy's Law.
- Prior treatment with orlotamab, enoblituzumab, or other B7-H3 targeted agents for
- Treatment with systemic cancer therapy within 3 weeks, investigational therapy within
4 weeks; 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.
- Clinically significant cardiovascular disease.
- Clinically significant pulmonary compromise or requirement for supplemental oxygen.
- History of clinically-significant cardiovascular disease.
- 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.
- Known positive testing for human immunodeficiency virus or history of acquired immune
- History of allogeneic bone marrow, stem cell, or solid organ transplant.
- Trauma or major surgery within 4 weeks of first study drug administration.