A Study of PRT1419 in Patients With Advanced Solid Tumors

Sponsor
Prelude Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04837677
Collaborator
(none)
30
Enrollment
4
Locations
1
Arm
24.6
Anticipated Duration (Months)
7.5
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 in Patients With Advanced Solid Tumors
Actual Study Start Date :
Aug 11, 2021
Anticipated Primary Completion Date :
Aug 31, 2023
Anticipated Study Completion Date :
Aug 31, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: PRT1419

PRT1419 will be administered by intravenous infusion

Drug: PRT1419
PRT1419 will be administered by intravenous infusion

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicities (DLT) of PRT1419 [Baseline through Day 28]

    Dose limiting toxicities will be evaluated through the first cycle

  2. Maximally tolerated dose (MTD) and/or optimal biological dose (OBD) [Baseline through approximately 2 years]

    The MTD and/or OBD will be established for further investigation in participants with advanced solid tumors.

  3. Recommended phase 2 dose (RP2D) and schedule of PRT1419 [Baseline through approximately 2 years]

    The RP2D will be established for further investigation in participants with advanced solid tumors.

Secondary Outcome Measures

  1. Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments [Baseline through approximately 2 years]

    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)

  2. Pharmacokinetic profile of PRT1419: maximum observed plasma concentration [Baseline through approximately 2 years]

    PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration

  3. Anti-tumor activity of PRT1419: measurement of objective responses [Baseline through approximately 2 years]

    Anti-tumor activity of PRT1419 will be based on the measurement of objective responses

  4. Progression-free survival [Baseline through approximately 2 years]

    Progression-free survival will be calculated from the first administration of PRT1419 until death or until the criteria for disease progression are met

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Sarah Cannon Research Institute at HealthONEDenverColoradoUnited States80218
2Florida Cancer SpecialistsLake MaryFloridaUnited States32746
3Florida Cancer SpecialistsSarasotaFloridaUnited States34232
4Tennessee OncologyNashvilleTennesseeUnited States37203

Sponsors and Collaborators

  • Prelude Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Prelude Therapeutics
ClinicalTrials.gov Identifier:
NCT04837677
Other Study ID Numbers:
  • PRT1419-02
First Posted:
Apr 8, 2021
Last Update Posted:
Nov 18, 2021
Last Verified:
Aug 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Prelude Therapeutics

Study Results

No Results Posted as of Nov 18, 2021