Overview
This is a multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of ATG-019, a dual inhibitor of PAK4 and NAMPT, alone or co-administered with starting dose of 500 mg niacin ER in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL).
Description
This is a multi-center, open-label clinical study with separate Dose Escalation and Expansion Phases to assess preliminary safety, tolerability, and efficacy of ATG-019, a dual inhibitor of PAK4 and NAMPT, alone or co-administered with starting dose of 500 mg niacin ER (may be titrated to 1,000 mg of daily dose, per label), in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL) for which all standard therapeutic options considered useful by the investigator have been exhausted and with PD at study entry. The MTD and RP2D will be determined.
Eligibility
Inclusion Criteria:
- Written informed consent obtained prior to any screening procedures and in accordance with local and institutional guidelines.
- Age 18 years.
- Patients with histologically or cytologically confirmed, NHL or advanced solid tumors which have progressed despite standard therapy, for whom no standard therapy exists, or who have refused standard therapy.
- Patients must have objective evidence of PD on study entry:
- Advanced solid tumors: Measureable disease as defined by RECIST 1.11.
- NHL: Measureable disease including target lesion(s) as defined by the Cheson 2014 Classification2 for initial evaluation and staging.
- Eastern Cooperative Oncology Group (ECOG) performance status of 1.
- Adequate hepatic function.
- Adequate renal function.
- Life expectancy of 3 months.
- Adequate hematopoietic function.
- Female patients of child-bearing potential must agree to use dual methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at Screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential.
Exclusion Criteria:
- Female patients who are pregnant or lactating.
- Time since the last prior therapy for treatment of advanced solid tumors or NHL**:
- Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anti-cancer therapy 4 weeks prior to C1D1.
- Palliative steroids for disease related symptoms within 7 days prior to C1D1.
- Known central nervous system metastases.
- Major surgery within 4 weeks before C1D1.
- Impaired cardiac function or clinically significant cardiac diseases.
- Active infection with completion of therapeutic antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
- Patients diagnosed with tuberculosis and had received treatment.
- Patients with a known history of human immunodeficiency virus (HIV).
- Known, active hepatitis A, B, or C infection.
- Serious psychiatric or medical conditions that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give consent.