a study of prt1419 in patients with advanced solid tumors

Conditions: Sarcoma; Melanoma; Lung Cancer; Breast Cancer; Esophageal Cancer; Cervical Cancer; Head and Neck Cancer

Summary: this is a phase 1 dose-escalation study of prt1419, a myeloid cell leukemia 1 (mcl1) inhibitor, in patients with advanced solid tumors. the purpose of this study is to define the dosing schedule, maximally tolerated dose and/or estimate the optimal biological dose to be used in subsequent development of prt1419.

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.

Eligibility criteria:
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.

Keywords: mcl1