A Study of PRT1419 in Patients With Advanced Solid Tumors

Sponsor
Prelude Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04837677
Collaborator
(none)
30
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1
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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

Arm Intervention/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

Site City State Country Postal Code
1 Sarah Cannon Research Institute at HealthONE Denver Colorado United States 80218
2 Florida Cancer Specialists Lake Mary Florida United States 32746
3 Florida Cancer Specialists Sarasota Florida United States 34232
4 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
5 Thomas Jefferson University, Sidney Kimmel Cancer Center Philadelphia Pennsylvania United States 19107
6 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
7 Tennessee Oncology Nashville Tennessee United States 37203

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:
May 27, 2022
Last Verified:
May 1, 2022
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 May 27, 2022