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

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

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.

Inclusion Criteria:

1. Patients with confirmed R/R CLL/SLL according to the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
2. 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.
3. Have at least one measurable lesion.
4. Age ≥18 years, regardless of sex.
5. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
6. Life expectancy ≥ 12 weeks.
7. Adequate coagulation function, liver and kidney function, bone marrow hematopoietic function.
8. Toxicities from prior anti-tumor therapy have recovered to Grade ≤1 according to NCI CTCAE v5.0.
9. 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.
10. Participation is voluntary, requiring signed informed consent and compliance with the treatment regimen and visit schedule.

Exclusion Criteria:

1. Known hypersensitivity to Lacutoclax or any of its excipients.
2. Prior treatment with a BCL-2 family inhibitor.
3. History of or currently suspected Richter's syndrome.
4. Known or suspected central nervous system (CNS) involvement.
5. 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.
6. 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.
7. Received corticosteroids for antitumor purposes, herbal medicines for antitumor treatment, or localized radiotherapy within 14 days prior to the first dose of study treatment.
8. 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.
9. 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.
10. Major cardiovascular or cerebrovascular events within 6 months prior to the first dose of study treatment.
11. Presence of any severe and/or uncontrolled systemic disease.
12. Impaired cardiac function.
13. Any uncontrolled systemic infection.
14. Conditions that may impair oral drug administration or significantly affect absorption or pharmacokinetics of the study drug.
15. Unable to discontinue moderate or strong CYP3A inhibitors or inducers, or sensitive CYP2C8 substrates during the study period.
16. Primary autoimmune disease requiring immunosuppressive therapy.
17. Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.