A Study of PRT1419 in Patients With Advanced Solid Tumors

This is a multicenter, open-label, dose-escalation Phase 1 study of PRT1419, a MCL1 inhibitor, evaluating patients with relapsed or refractory solid tumors, including breast, lung, sarcoma and melanoma as part of a 28-day treatment cycle. The study will employ a "3+3" dose escalation design. The dose may be escalated until a dose limiting toxicity is identified.

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
• Left ventricular ejection fraction of ≥ 50%
• Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use a highly effective method of contraception during the trial
• Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ Grade 1)
• All patients on prior investigational agents must wait at least 5 half-lives of the agent in question, or 28 days, whichever is longer before study entry
• Most recent lab values meet the following criteria:

• Absolute neutrophil count > 1.0 x 10^3/μL;
• Platelet count > 75,000/μL;
• Hemoglobin > 9.0 g/dL
• Histologically confirmed advanced or metastatic solid tumor indicated below that is relapsed, refractory, or intolerant to available therapies with known benefit:

• Sarcoma not amendable to curative treatment with surgery or radiotherapy;
• Melanoma (non-resectable or metastatic);
• Small cell lung cancer (extensive-stage);
• Non-small cell lung cancer;
• Triple negative breast cancer (histopathologically or cytologically confirmed).
• Esophageal cancer
• Cervical cancer
• Head and neck cancer

Exclusion criteria

• Known hypersensitivity to any of the components of PRT1419
• Primary malignancies of the CNS, or uncontrolled CNS metastases, including impending spinal cord compression
• Female patients who are pregnant or lactating
• Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
• Mean QTcF interval of >480 msec
• History of heart failure, additional risk factors for arrhythmias or requiring concomitant medications that prolong the QT/QTc interval
• HIV positive; known active hepatitis B or C
• Uncontrolled intercurrent illnesses
• Treatment with strong inhibitors of CYP2C8
• Prior exposure to an MCL1 inhibitor
• History of another malignancy except:

• Malignancy treated with curative intent with no known active disease for >2 years at study entry;
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
• Adequately treated carcinoma in situ without evidence of disease;
• Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.