Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab in Refractory Cancer

Primary Outcome Measures

• Number of participants with adverse events [ Time Frame: one year ]

Secondary Outcome Measures

• Peak plasma concentration [ Time Frame: 7 weeks ] PK of MGA271 in combination with pembrolizumab
• Number of participants that develop anti-drug antibodies [ Time Frame: One year ] Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
• Change in tumor volume [ Time Frame: Weeks 6, 15, 24, 33, 42, 51 ] Anti-tumor activity of MGA271 in combination with pembrolizumab using both conventional RECIST 1.1 and immune-related RECIST criteria.

Eligibility

Inclusion Criteria

Histologically-proven, unresectable, locally advanced or metastatic melanoma, SCCHN, NSCLC, and other cancers 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 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

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 cancer therapy. For squamous cell carcinoma, or adenocarcinoma without known activating mutation: the prior systemic therapy is at least one platinum analogue. For adenocarcinoma with known activating driver mutation: the prior systemic therapy is at least TKI directed

Mesothelioma that has progressed during or following at least 1 and up to 3 prior systemic treatments for unresectable locally advanced or metastatic disease. The prior systemic chemotherapy must have included a pemetrexed (anti-folate)-based regimen in combination with platinum agent. For patients in whom pemetrexed was contraindicated or not tolerated or not an approved therapy (e.g., peritoneal mesothelioma), prior therapy with a first-line platinum-based regimen is required.

Urothelial cancer arising in the bladder, renal pelvis, ureter or urethra that has progressed during or following at least 1 and up to 5 prior systemic treatments for unresectable locally advanced or metastatic disease (includes anti-PD-L1,anti-PD-1, but excludes other experimental therapies). Patients must have received at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], dose-dense methotrexate/vinblastine/doxorubicin/cisplatin [DDMVAC], or carboplatinum/gemcitabine). No more than 5 prior systemic regimens allowed.

Thyroid cancer that has progressed during or following at least 1 and up to 5 prior chemotherapy regimen(s). Prior therapy excludes experimental therapies given in Phase 1 trials.

Pancreatic cancer that has progressed during or following at least 1 and up to 3 prior chemotherapy regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.

Ovarian cancer that has progressed during or following at least 2 and up to 4 prior therapeutic regimens (e.g., 2 prior platinum containing regimens or if platinum resistant, a liposomal doxorubicin or topotecan containing regimen). Prior therapy excludes experimental therapies given in Phase 1 trials

Colon cancer that has progressed during or following at least 2 and up to 4 prior therapeutic regimens (e.g., fluoropyrimidine and/or irinotecan and/or oxaliplatin and/or anti-EGFR antibody containing regimens). Prior therapy excludes experimental therapies given in Phase 1 trials.

Prostate cancer that has progressed during or following at least 1 and up to 5 prior therapeutic regimens (e.g., abiraterone, enzalutamide, docetaxel). Prior therapy excludes experimental therapies given in Phase 1 trials.

Soft tissue sarcoma that has progressed during or following at least 1 and up to 5 prior therapeutic regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.

TNBC that has progressed during or following at least 1 and up to 5 prior therapeutic regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.

ccRCC that has progressed during or following at least 1 and up to 5 prior therapeutic regimens. Prior therapy excludes experimental therapies given in Phase 1 trials.

Measurable disease per RECIST 1.1 criteria

Easter Cooperative Oncology Group (ECOG) performance status 0 or 1

Acceptable laboratory parameters and adequate organ reserve.

Exclusion Criteria

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 deficiency syndrome

Known hypersensitivity to recombinant proteins, polysorbate 80, or any excipient contained in the drug or vehicle formulation for MGA271 or pembrolizumab.