Advanced Solid Tumor Clinical Trial
Official title:
Phase I Trial of PCLX-001 in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma and Advanced Solid Malignancies
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).
Status | Recruiting |
Enrollment | 60 |
Est. completion date | December 31, 2024 |
Est. primary completion date | October 28, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. 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. 2. Male or female patients aged = 18 years 3. Dose Escalation 1. 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. 2. 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. 4. Patients must have evaluable or measurable disease. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 6. Life expectancy of at least 12 weeks 7. Patients must have adequate bone marrow, liver, kidney and cardiac function. 8. Patients must have adequate coagulation. 9. Women of childbearing potential must have a negative pregnancy test. 10. 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. Exclusion Criteria: 1. Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study. 2. 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. 3. Uncontrolled arterial hypertension despite optimal medical management. 4. Moderate or severe hepatic impairment. 5. Patients with known human immunodeficiency virus (HIV) infection. 6. Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment. 7. Infections not responding to therapy or active clinically serious infections. 8. 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. 9. Current or past history of central nervous system (CNS) lymphoma. 10. Uncontrolled seizure disorder requiring therapy. 11. 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. 12. Evidence or history of bleeding disorder within 4 weeks before the first dose of study drug. 13. Serious, non-healing wound, ulcer, or bone fracture. 14. Any malabsorption condition. 15. Breastfeeding. Female patients must not breastfeed during treatment and until 4 months after last study drug administration. 16. Treatment with systemic steroids (prednisone dose =10 mg/day or equivalent dose). 17. Acute toxic effects of previous anticancer chemotherapy or immunotherapy that have not yet stabilized or if significant post-treatment toxicities have been observed. 18. Radiotherapy for target lesions during study or within 3 weeks before the first dose of study drug. 19. Major surgery or significant trauma within 4 weeks before the first dose of study drug. 20. Concomitant participation in another clinical study with investigational medicinal product(s). 21. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. 22. Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first administration of study drug. Strong CYP3A4 inhibitors and inducers are prohibited during the study and until the active follow up visit. 23. Clinically relevant findings in the ECG. |
Country | Name | City | State |
---|---|---|---|
Canada | Cross Cancer Institute | Edmonton | Alberta |
Canada | CR Centre Hospitalier de l'Université de Montréal - CHUM | Montréal | Quebec |
Canada | Princess Margaret Hospital | Toronto | Ontario |
Canada | BC Cancer - Vancouver | Vancouver | British Columbia |
Lead Sponsor | Collaborator |
---|---|
Pacylex Pharmaceuticals |
Canada,
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Assess the pharmacodynamic (PD) effects of PCLX-001 in patients with B-cell lymphomas | Collection of blood samples for exploratory biomarker research is also a part of this trial. Specimens will be stored and may be used for research purposes to identify biomarkers useful for predicting and monitoring PCLX-001. | Measured during every cycle (Cycles 1, 2, 3, 4, etc.) of treatment (Cycle length is 28 days) | |
Primary | 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. | Cycle length is 28 days | |
Primary | To determine the time to maximum plasma level (Tmax) of PCLX-001 | Tmax is the time at which the maximum plasma concentration of PCLX-001 is achieved. | Measured on Cycles 1, 2 and 3 (Cycle length is 28 days) | |
Primary | To determine the maximum plasma level (Cmax) of PCLX-001 | Cmax is the maximum plasma concentration of PCLX-001. | Measured on Cycles 1, 2 and 3 (Cycle length is 28 days) | |
Secondary | To evaluate the clinical response rate in patients treated with PCLX-001 with advanced solid malignancies | Tumor response and progression of solid tumors and NHL will be evaluated by the investigator at each study center | Tumor measurements and NHL for efficacy evaluation will be made at initiation and at the end of every 2nd cycle (each cycle is 28 days) |
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