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

• ClinicalTrials.gov Identifier: NCT04543305
• Recruitment Status: Recruiting
• First Posted: September 10, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Prelude Therapeutics
• Information provided by (Responsible Party): Prelude Therapeutics

Tracking Information

• First Submitted Date: September 2, 2020
• First Posted Date: September 10, 2020
• Last Update Posted Date: December 8, 2020
• Actual Study Start Date: September 28, 2020
• Estimated Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 2, 2020)

• To describe dose limiting toxicities (DLT) of PRT1419 [ Time Frame: Baseline through Day 28 ]
  Dose limiting toxicities will be evaluated through the first cycle
• To determine the maximally tolerated dose (MTD) and/or optimal biological dose (OBD) [ Time Frame: Baseline through approximately 2 years ]
  The MTD and/or OBD will be established for further investigation in participants with multiple myeloma, Non-Hodgkin's Lymphoma, acute myeloid leukemia and myelodysplastic syndrome
• To determine the recommended phase 2 dose (RP2D) and schedule of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
  The RP2D will be established for further investigation in participants with multiple myeloma, Non-Hodgkin's Lymphoma, acute myeloid leukemia and myelodysplastic syndrome

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 2, 2020)

• To describe the adverse event profile and tolerability of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
  Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
• To describe the pharmacokinetic profile of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
  PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration
• To describe any anti-tumor activity of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
  Anti-tumor activity of PRT1419 will be based on the measurement of objective responses

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
• Official Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
• Brief 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.
• Detailed Description: This is a multicenter, open-label, dose-escalation Phase 1 study of PRT1419, a MCL1 inhibitor, evaluating patients in two cohorts as part of a 28-day treatment cycle in adult patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Cohort A will evaluate PRT1419 administered as monotherapy in patients with either AML and/or high-risk MDS. Cohort B will evaluate PRT1419 administered as monotherapy in patients with NHL or MM. 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
• Study Phase: Phase 1
• Study Design: Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Multiple Myeloma
• Acute Myeloid Leukemia
• Non Hodgkin Lymphoma
• Myelodysplastic Syndromes

Intervention

Drug: PRT1419

PRT1419 will be administered orally

Study Arms

Experimental: PRT1419

PRT1419 will be administered orally

Intervention: Drug: PRT1419

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 2, 2020): 36
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2022
• Estimated Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Eligibility 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
• 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
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 302-644-5434; PRT1419-01Study@Preludetx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04543305
• Other Study ID Numbers: PRT1419-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Prelude Therapeutics
• Study Sponsor: Prelude Therapeutics
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Prelude Therapeutics
• Verification Date: December 2020