A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies

• Status: Recruiting
• Trial end date: 2022-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia 1 (MCL1) inhibitor, in patients with relapsed/refractory hematologic malignancies. 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prelude Therapeutics

Criteria

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 14 days, whichever is longer before study entry

• AML patients only: Pathologically confirmed diagnosis of AML as defined by the WHO Classification and patients with targeted mutations must have been treated with appropriate therapy for their disease

• White blood cell count < 25 x 10^9/L. Hydrea or leukapheresis are permitted to meet this criterion.

• CMML patients only: intermediate-2 or high risk per CMML-specific prognostic scoring system (CPSS) or clinical/molecular CPSS (CPSS-mol) criteria. Must have failed prior therapy with a hypomethylating agent.

• MDS patients only: Intermediate, high, or very high risk by International Prognostic Scoring System-Revised [IPSS-R] criteria that is relapsed or refractory to approved therapies or MDS/MPN Overlap Syndrome (displaying both fibrosis and dysplastic features).

• NHL patients only: Histologically or cytologically confirmed NHL, including B- and T-cell lymphomas that is relapsed or refractory or intolerant to approved therapies. Must have one lesion that can be measured for response

• MM patients only: Measurable disease defined by one or more of the following: Serum M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours, Serum Free Light Chain (sFLC) > 10 mg/dL with normal serum FLC ratio. Presence of soft tissue plasmacytoma confirmed by imaging

• NHL and MM patients only: must have the following lab values within 14 days prior to study Day 1:

• ANC ≥1.0 x 10^3 μL

• Platelet count ≥50,000 μL

Exclusion Criteria:

• Known hypersensitivity to any of the components of PRT1419

• Female patients who are pregnant or lactating

• Mean QTcF interval of >480 msec

• History of heart failure, additional risk factors for arryhthmias or requiring concomitant medications that prolong the QT/QTc interval

• Hematopoietic stem-cell transplant < 90 days or have GVHD Grade >1 at study entry

• Uncontrolled intercurrent illnesses

• Treatment with strong inhibitors of CYP2C8 and/or P-glycoprotein for which there are no therapeutic substitutions

• Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption

• HIV positive; known active hepatitis B or C

• 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.