Clinical Trial 18393

Cancer Type: Thoracic
Interventions:MGA271; Pembrolizumab (Keytruda)

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Scott Antonia

Overview

Study Title

A Phase 1, Open-Label, Dose Escalation Study of MGA271 in Combination with Pembrolizumab in Patients with B7-H3-Expressing Melanoma, Squamous Cell Cancer of the Head and Neck, or Squamous Cell Non-Small Cell Lung Cancer

Summary

The purpose of this study is to evaluate the safety of enoblituzumab (MGA271) in combination with Keytruda (pembrolizumab) when given to patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non small cell lung cancer (NSCLC), and other B7-H3 expressing cancers. The study will also evaluate what is the highest dose of enoblituzumab that can be given safely when given with pembrolizumab. Assessments will also be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics) and to evaluate potential anti-tumor activity of MGA271 in combination with pembrolizumab.

Objective

The primary objective of this study is to characterize the safety, tolerability, dose-limiting toxicities (DLT), andmaximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of MGA271when administered intravenously (IV) weekly in combination with 2 mg/kg pembrolizumab administered IV every 3 weeks to patients with B7-H3 expressing, unresectable locally-advanced or metastatic melanoma,SCCHN, or squamous cell NSCLC.

Inclusion Criteria

  • Histologically-proven, unresectable, locally advanced or metastatic melanoma, Squamous Cell Cancer of the Head and Neck (SCCHN), Non-Small Cell Lung Cancer (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. Patients 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. Additional criteria may apply.
  • 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. Must have received at least one platinum-containing regimen. 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. 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. . 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.
  • Triple-negative breast cancer (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.
  • Clear cell renal cell carcinoma (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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Easter Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Acceptable laboratory parameters and adequate organ reserve.

  • Exclusion Criteria

  • A history of symptomatic central nervous system metastases, unless treated and asymptomatic
  • 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.