A Study of PRT1419 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief 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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 in Patients With Advanced Solid Tumors

Conditions
-----------------
Sarcoma, Melanoma, Lung Cancer, Breast Cancer, Esophageal Cancer, Cervical Cancer, Head and Neck Cancer

Intervention / Treatment
-----------------
* Drug: PRT1419


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRT1419<br>PRT1419 will be administered by intravenous infusion | Drug: PRT1419<br>* PRT1419 will be administered by intravenous infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLT) of PRT1419 | Dose limiting toxicities will be evaluated through the first cycle | Baseline through Day 28 | 
| Maximally tolerated dose (MTD) and/or optimal biological dose (OBD) | The MTD and/or OBD will be established for further investigation in participants with advanced solid tumors. | Baseline through approximately 2 years | 
| Recommended phase 2 dose (RP2D) and schedule of PRT1419 | The RP2D will be established for further investigation in participants with advanced solid tumors. | Baseline through approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments | Safety and tolerability will be assessed by recording adverse events (AEs) and serious adverse events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) | Baseline through approximately 2 years | 
| Pharmacokinetic profile of PRT1419: maximum observed plasma concentration | PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration | Baseline through approximately 2 years | 
| Anti-tumor activity of PRT1419: measurement of objective responses | Anti-tumor activity of PRT1419 will be based on the measurement of objective responses | Baseline through approximately 2 years | 
| Progression-free survival | Progression-free survival will be calculated from the first administration of PRT1419 until death or until the criteria for disease progression are met | Baseline through approximately 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MCL1