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
- 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
- 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
- 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