A Study of PRT1419 in Patients With Advanced Solid Tumors

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.