A Study of PRT1419 in Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04837677
• Other study ID #: PRT1419-02
• Status: Completed
• Phase: Phase 1
• Start date: August 11, 2021
• Est. completion date: February 6, 2023

Study information

• Verified date: March 2023
• Source: Prelude Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 6, 2023
• Est. primary completion date: February 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Cervical Cancer
• Esophageal Cancer
• Head and Neck Cancer
• Lung Cancer
• Melanoma
• Sarcoma

Intervention

Drug:
• PRT1419
PRT1419 will be administered by intravenous infusion

Locations

Country	Name	City	State
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Florida Cancer Specialists	Lake Mary	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Prelude Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLT) of PRT1419	Dose limiting toxicities will be evaluated through the first cycle	Baseline through Day 28
Primary	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
Primary	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	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
Secondary	Pharmacokinetic profile of PRT1419: maximum observed plasma concentration	PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration	Baseline through approximately 2 years
Secondary	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
Secondary	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