Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of P276-00 in Patients With Relapsed and/or Refractory Mantle Cell Lymphoma

Trial Information

Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of P276-00 in Patients With Relapsed and/or Refractory Mantle Cell Lymphoma

Despite response rates of up to 97% with first-line standard or high-intensity chemotherapy,
with or without stem-cell transplantation, most patients of mantle cell lymphoma
(MCL)relapse.Prognosis of MCL after first relapse is very poor with median survival of
around 1 to 2 years. Therefore, novel therapies are required for relapsed and/or refractory
MCL.Overexpression of Cyclin D1 as a result of t(11;14)(q13;q32) translocation is the
hallmark of MCL.It is postulated that Cyclin D1 may also have an oncogenic role independent
of pRb in MCL.Therefore, inhibition of Cdk4-Cyclin D1 is a potentially promising target in
MCL. P276-00 is a potent Cdk4-Cyclin D1 inhibitor worth exploring for its efficacy in MCL.
Hence, this Phase II study is planned to examine the efficacy and safety of P276-00 in the
treatment of patients with relapsed and/or refractory MCL.

This is an open-label, single-arm, 2-stage trial. Approximately 35 patients are planned to
be enrolled into the study to obtain a total of 25 efficacy evaluable patients (patients who
complete at least 2 cycles of study treatment and have tumor measurements at the end of 2
cycles). A total of 15 efficacy evaluable patients are planned to be treated in Stage I of
the study. If ≥1 response (CR or PR) of any duration or ≥2 stable disease (SD) for ≥4
cycles are seen in the Stage I, then the study will continue into Stage II, in which
additional patients will be treated until there are 10 additional efficacy evaluable
patients.The study is divided into 3 periods: Screening, Treatment, and Follow-up. During
the Screening Period, patients will provide written informed consent and be evaluated for
inclusion and exclusion criteria. During the Treatment Period, patients will be administered
P276-00 as intravenous (iv) infusion on Days 1 to 5 of each 21-day cycle for a minimum of 6
cycles and a maximum of 12 cycles, or until progressive disease (PD) or unacceptable
toxicity occurs. Safety and efficacy evaluations will be done on Days 1 to 5 and 11 of each
cycle, and on Day 21 of every 2 cycles. Pharmacokinetic (PK) assessments will be done on
Cycle 1, Day 1 (pre-dose and post-dose time points), and optional biomarker assessments will
be done pre-dose within 4 weeks of Day 1 and post-dose on Day 4 or 5. The End-of-Last-Cycle
Visit will occur at the end of Cycle 6, or if the patient continues study treatment beyond
Cycle 6, it will occur at the end of the patient's last cycle; if the patient discontinues
early, these assessments will be done as an Early Exit Visit. The Follow-up Visit will
occur 4 weeks (±1 week) after the End-of-Last-Cycle Visit (or Early Exit Visit) for final
safety assessments.Objective response rate is the primary end point for this study. Response
evaluation will be performed using the International Working Group (IWG) revised response
criteria for malignant lymphoma.