Study of PCLX-001 in R/R Advanced Solid Malignancies and B-cell Lymphoma

NCT04836195 | Completed Phase 1 Results

• 1 other identifier: PCLX-001-01
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase I dose-escalation study of oral PCLX-001, conducted in a multicenter, non-randomized, open-label, non-controlled design. The study is comprised of two parts: Part A (single-agent dose escalation) and Part B (single-agent expansion cohorts).

Conditions

B-cell Non Hodgkin Lymphoma; Advanced Solid Tumor

Outcome Measures

Primary Outcomes (1)

• To Determine, During the Dose Escalation Phase, the Recommended Dose of PCLX-001 for the Dose Expansion Phase of the Trial.

  The recommended dose will be the dose level below that for the cohort in which maximum tolerated dose (MTD) was reached/exceeded. MTD will have been reached when 2 or more patients in a cohort experience DLT.

  Through study completion, an average of ~90 days

Study Arms (7)

PCLX-001 intervention 20mg

EXPERIMENTAL

Cohort 1: Participants were administered 20mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.

Drug: PCLX-001 - 20mg

PCLX-001 intervention 40mg

EXPERIMENTAL

Cohort 2: Participants were administered 40mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.

Drug: PCLX-001 - 40mg

PCLX-001 intervention 70mg

EXPERIMENTAL

Cohort 3: Participants were administered 70mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.

Drug: PCLX-001 - 70mg

PCLX-001 intervention 100mg

EXPERIMENTAL

Cohort 4: Participants were administered 100mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.

Drug: PCLX-001 - 100mg

PCLX-001 intervention 140mg

EXPERIMENTAL

Cohort 5: Participants were administered 140mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.

Drug: PCLX-001 - 140mg

PCLX-001 intervention 210mg

EXPERIMENTAL

Cohort 6: Participants were administered 210mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.

Drug: PCLX-001 - 210mg

PCLX-001 intervention 280mg

EXPERIMENTAL

Cohort 7: Participants were administered 280mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.

Drug: PCLX-001 - 280mg

Interventions

PCLX-001 - 20mg DRUG

20mg daily oral pills

Also known as: zelenirstat

PCLX-001 intervention 20mg

PCLX-001 - 40mg DRUG

40mg daily oral pills

Also known as: zelenirstat

PCLX-001 intervention 40mg

PCLX-001 - 70mg DRUG

70mg daily oral pills

Also known as: zelenirstat

PCLX-001 intervention 70mg

PCLX-001 - 100mg DRUG

100mg daily oral pills

Also known as: zelenirstat

PCLX-001 intervention 100mg

PCLX-001 - 140mg DRUG

140mg daily oral pills

Also known as: zelenirstat

PCLX-001 intervention 140mg

PCLX-001 - 210mg DRUG

210mg daily oral pills

Also known as: zelenirstat

PCLX-001 intervention 210mg

PCLX-001 - 280mg DRUG

280mg daily oral pills

Also known as: zelenirstat

PCLX-001 intervention 280mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained before any study-specific procedures are performed.
• Male or female patients aged ≥ 18 years
• Dose Escalation
• Participants with histologically-confirmed advanced solid tumor who have failed at least one prior therapy and/or are not eligible for therapies expected to provide clinical benefit.
• Histologically-confirmed B-cell lymphomas that are expected to express CD20 including DLBCL, HGBL, FL (grades 1 to 3b), MCL, and Burkitt lymphoma who have failed at least two prior therapies and/or are not eligible for therapies expected to provide clinical benefit (including autologous stem cell transplantation). Transformed large B-cell lymphoma patients are eligible. FL patients should meet criteria for requiring treatment.
• Dose Expansion Cohort A: Participants with histologically-confirmed advanced breast, NSCLC, SCLC, colorectal, and bladder cancers who have failed at least one prior therapy and/or are not eligible for therapies expected to provide clinical benefit.
• Cohort B: Participants with histologically-confirmed R/R B-cell lymphomas that are expected to express CD20 including DLBCL, HGBL, FL (grades 1-3a), FL (grade 3b), MCL, and Burkitt lymphoma who have failed at least two prior therapies and/or are not eligible for therapies expected to provide clinical benefit. Transformed large B-cell lymphoma patients are eligible. FL patients should meet criteria for requiring treatment.
• Patients must have evaluable or measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy of at least 12 weeks
• Patients must have adequate bone marrow, liver, kidney and cardiac function.
• Patients must have adequate coagulation.
• Women of childbearing potential must have a negative pregnancy test.
• Women of childbearing potential and fertile men must agree to use adequate contraception when sexually active from signing of the informed consent form for the full study until at least 6 months after the last study drug administration.

You may not qualify if:

• Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study.
• History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class \> II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry, or uncontrolled cardiac arrhythmias.
• Uncontrolled arterial hypertension despite optimal medical management.
• Moderate or severe hepatic impairment.
• Patients with known human immunodeficiency virus (HIV) infection.
• Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
• Infections not responding to therapy or active clinically serious infections.
• Symptomatic metastatic brain or meningeal tumors unless the patient is \> 3 months from definitive therapy, has a stable imaging study and is clinically stable. Patients with asymptomatic brain metastases must not be on steroid therapy.
• Current or past history of central nervous system (CNS) lymphoma.
• Uncontrolled seizure disorder requiring therapy.
• History of organ allograft transplantation or autologous stem cell transplantation ≤ 3 months prior to the first dose of study drug. Patients who received prior CAR-T or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to study drug administration.
• Evidence or history of bleeding disorder within 4 weeks before the first dose of study drug.
• Serious, non-healing wound, ulcer, or bone fracture.
• Any malabsorption condition.
• Breastfeeding. Female patients must not breastfeed during treatment and until 4 months after last study drug administration.

Sponsors & Collaborators

• Pacylex Pharmaceuticals: lead

Study Sites (4)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer - Vancouver

Vancouver, British Columbia, V5Z4E6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CR Centre Hospitalier de l'Université de Montréal - CHUM

Montreal, Quebec, H2X 0A9, Canada

Location

Related Publications (2)

• Beauchamp E, Yap MC, Iyer A, Perinpanayagam MA, Gamma JM, Vincent KM, Lakshmanan M, Raju A, Tergaonkar V, Tan SY, Lim ST, Dong WF, Postovit LM, Read KD, Gray DW, Wyatt PG, Mackey JR, Berthiaume LG. Targeting N-myristoylation for therapy of B-cell lymphomas. Nat Commun. 2020 Oct 22;11(1):5348. doi: 10.1038/s41467-020-18998-1.

  PMID: 33093447 BACKGROUND

• Sangha R, Jamal R, Spratlin J, Kuruvilla J, Sehn LH, Beauchamp E, Weickert M, Berthiaume LG, Mackey JR. A first-in-human phase I trial of daily oral zelenirstat, a N-myristoyltransferase inhibitor, in patients with advanced solid tumors and relapsed/refractory B-cell lymphomas. Invest New Drugs. 2024 Aug;42(4):386-393. doi: 10.1007/s10637-024-01448-w. Epub 2024 Jun 5.

  PMID: 38837078 RESULT

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: VP Operations
• Organization: Pacylex Pharmaceuticals

ryan.heit@pacylex.com

1 (888) 580-4483

Study Officials

• Randeep Sangha

  Cross Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: For Part A dose-escalation, patients will be enrolled in cohorts of 3 to 6 patients to each dose level. Six patients will be treated at the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D).

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 8, 2021
• Study Start: September 14, 2021
• Primary Completion: October 28, 2024
• Study Completion: October 28, 2024
• Last Updated: April 17, 2025
• Results First Posted: April 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)