Dose Escalation Safety Study of TL32711 in Adults With Refractory Solid Tumors or Lymphoma

A Phase 1, Open-Label, Non-randomized, Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TL32711 in Adults With Refractory Solid Tumors or Lymphoma

A Phase 1 open-label, non-randomized dose escalation study to determine the maximum tolerated dose (MTD) and characterize the safety and tolerability of Birinapant (TL32711).

The purpose of this Phase 1 open-label, non-randomized dose escalation study is to determine the maximum tolerated dose (MTD) and characterize the safety and tolerability of Birinapant (TL32711) when administered as a 30 minute intravenous infusion once weekly for three weeks per repeated 4 week intervals in subjects with refractory solid tumors or lymphoma. Additionally study will assess anti-tumor activity, pharmacokinetics, and exploratory biomarkers as a measurement of pharmacodynamic effects.

Key Inclusion Criteria:

• Advanced metastatic or unresectable malignancy that is refractory to currently available standard therapies or no effective therapy exists. The subject's malignancy must be confirmed by prior pathologic study.
• Evaluable disease (measurable or non-measurable) by Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1) or Revised Response Criteria for Malignant Lymphoma (RRCML) (Cheson 2007).
• Life expectancy greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Adequate renal function, defined as serum creatinine ≤ 1.5 X upper limit of normal (ULN), or calculated creatinine clearance ≥ 60 ml/min.
• Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 3 X ULN and total bilirubin < 1.5 X ULN.
• Adequate bone marrow function, defined as absolute neutrophil (ANC) ≥ 1,500/mm3 (≥1.5 X106/L), platelet count ≥ 75,000/mm3 (≥ 75 X106/L), and hemoglobin ≥ 10 mg/dL in the absence of transfusion.

Key Exclusion Criteria:

• Recent anti-cancer treatment defined as:

  • Standard or investigational anti-cancer therapy within 4 weeks prior to first dose of TL32711. Exception: continued hormonal interventions for sensitive diseases.
  • Radiation therapy within 2 weeks prior to the first dose of TL32711.

• Clinically significant pulmonary illness resulting in Grade ≥ 2 hypoxia (National Cancer Institute Common Terminology criteria for Adverse Events [NCI CTCAE, v4]) or any requirement for supplemental oxygen, or pulse oximetry less than 90% saturation on room air.

• Symptomatic or uncontrolled brain metastases requiring current treatment (less than 4 weeks from last cranial radiation or 2 weeks from last steroids).

• Impaired cardiac function or clinically significant cardiac disease.

• Ongoing auto-immune disease or with history of an auto-immune disease within the past 5 years. Auto-immune disease include but are not limited to systemic lupus erythematosis, scleroderma, rheumatoid arthritis, psoriasis, psoriatic arthritis, ulcerative colitis and regional enteritis (Crohn's disease).

• Systemic or chronic topical corticosteroids or immunosuppressive therapy within 4 weeks prior to study entry or anticipated need of systemic corticosteroids or immunosuppressive therapy during study participation.

• Skin lesions of Grade ≥ 2 severity (NCI CTCAE v4), except alopecia.

• Lack of recovery of prior adverse events to Grade ≤1 severity (NCI CTCAE v 4) (except alopecia or neuropathy) due to medications administered prior to the first dose of TL32711.