A Study of PRT1419 in Patients With Advanced Solid Tumors

A Phase 1, Open-Label, Multicenter, Dose Escalation 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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Sarcoma; Cervical Cancer; Breast Cancer; Head and Neck Cancer; Esophageal Cancer; Lung Cancer
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Sidney Kimmel Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRT1419; PRT1419 will be administered by intravenous infusion	Drug: PRT1419; PRT1419 will be administered by intravenous infusion

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

Collaborators and Investigators

• Sponsor: Prelude Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): February 6, 2023
• Study Completion (Actual): February 6, 2023

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: MCL1
• Other Study ID Numbers: PRT1419-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No