A Study of Lacutoclax (LP-108) in Patients With Relapsed/Refractory CLL/SLL

Official title

A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Lacutoclax (LP-108) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Overview

The goal of this clinical trial is to evaluate the efficacy and safety of Lacutoclax, an oral selective BCL-2 inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Lacutoclax is a potent and selective BCL-2 inhibitor with relatively weaker inhibitory activity against BCL-XL and BCL-W. Preliminary clinical data have demonstrated promising efficacy and an acceptable safety profile in patients with CLL/SLL and other B-cell non-Hodgkin lymphomas (B-NHLs). This is an open-label, single-arm, multicenter Phase II study evaluating the efficacy and safety of oral Lacutoclax tablets in patients with relapsed or refractory CLL/SLL.

Interventions

• Drug Lacutoclax
  Participants will first undergo a dose ramp-up period of at least 4 days (Cycle 0: C0D1-C0D4), followed by continuous administration at the target dose of 400 mg once daily starting from Cycle 1. Each treatment cycle will last 28 days. Treatment will continue until disease progression, unacceptable toxicity, or fulfillment of other criteria for treatment discontinuation.

Primary outcome measures

• Overall Response Rate (ORR) assessed by Independent Review Committee (IRC) [Time frame: Up to approximately 28 months]

Secondary outcome measures (12)

• ORR assessed by Investigator(INV) [Time frame: Up to approximately 28 months]
• Complete response(CR) plus complete response with incomplete bone marrow recovery (CRi) rate (CRi applicable only to patients with CLL) assessed by IRC and INV, respectively [Time frame: Up to approximately 28 months]
• Time to response (TTR) assessed by IRC and INV, respectively [Time frame: Up to approximately 30 months]
• Duration of response (DOR) assessed by IRC and INV, respectively [Time frame: Up to approximately 30 months.]
• Time to first 50% reduction in absolute lymphocyte count (ALC) or normalization of ALC [Time frame: Up to approximately 28 months]
• Progression-free survival (PFS) assessed by IRC and INV, respectively [Time frame: Up to approximately 30 months]
• Overall Survival [Time frame: Up to approximately 30 months]
• Adverse events(AEs) as assessed by CTCAE v5.0 [Time frame: Up to approximately 30 months]
• Adverse drug reactions (ADRs) related to Lacutoclax [Time frame: Up to approximately 30 months]
• Serious adverse events (SAEs) [Time frame: Up to approximately 30 months]
• Maximum Plasma Concentration(Cmax) [Time frame: From 1 hour prior to administration to 24 hours post-dose]
• Time to Maximum Plasma Concentration (Tmax) [Time frame: From 1 hour prior to administration to 24 hours post-dose]

Eligibility criteria

Inclusion criteria

• Patients with confirmed R/R CLL/SLL according to the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
• Patients who had previously received standard therapy, experienced disease progression following the most recent line of treatment (excluding intolerance), and had at least one indication for treatment prior to enrollment.
• Have at least one measurable lesion.
• Age ≥18 years, regardless of sex.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
• Life expectancy ≥ 12 weeks.
• Adequate coagulation function, liver and kidney function, bone marrow hematopoietic function.
• Toxicities from prior anti-tumor therapy have recovered to Grade ≤1 according to NCI CTCAE v5.0.
• Male patients and female patients of childbearing potential must agree to use effective contraception during the study and for 90 days after the last dose of Lacutoclax. Female patients of childbearing potential must have a negative pregnancy test before study treatment and must not be breastfeeding. Male patients must not donate sperm during the study and for 90 days after the last dose of Lacutoclax.
• Participation is voluntary, requiring signed informed consent and compliance with the treatment regimen and visit schedule.

Exclusion criteria

• Known hypersensitivity to Lacutoclax or any of its excipients.
• Prior treatment with a BCL-2 family inhibitor.
• History of or currently suspected Richter's syndrome.
• Known or suspected central nervous system (CNS) involvement.
• Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT), or autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy within 90 days before the first dose of study treatment.
• Received antitumor therapy, investigational agents, major surgery, severe trauma, or live attenuated vaccines within 4 weeks or 5 half-lives prior to the first dose of study treatment.
• Received corticosteroids for antitumor purposes, herbal medicines for antitumor treatment, or localized radiotherapy within 14 days prior to the first dose of study treatment.
• Use of moderate or strong CYP3A inhibitors within 7 days prior to the first dose of study treatment, or consumption of grapefruit, grapefruit juice, starfruit, or Seville oranges within 3 days prior to dosing.
• Prior malignancy other than CLL/SLL within the past 2 years, except for curatively treated basal cell carcinoma, localized squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other malignancies considered cured.
• Major cardiovascular or cerebrovascular events within 6 months prior to the first dose of study treatment.
• Presence of any severe and/or uncontrolled systemic disease.
• Impaired cardiac function.
• Any uncontrolled systemic infection.
• Conditions that may impair oral drug administration or significantly affect absorption or pharmacokinetics of the study drug.
• Unable to discontinue moderate or strong CYP3A inhibitors or inducers, or sensitive CYP2C8 substrates during the study period.
• Primary autoimmune disease requiring immunosuppressive therapy.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Nanjing Medical University — Nanjing

Identifiers

NCT: NCT07609823 · LP-10821

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗