A Study of PRT1419 in Patients With Advanced Solid Tumors

Prelude Therapeutics

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Melanoma

Sarcoma

Esophageal Cancer

Lung Cancer

Head and Neck Cancer

Cervical Cancer

Treatments

Drug: PRT1419

Study type

Interventional

Funder types

Industry

Identifiers

NCT04837677

PRT1419-02

Details and patient eligibility

About

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.

Full 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.

Enrollment

26 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.