A Study of LP-168 in Participants With Relapse or Refractory B-Cell Lymphoma

Official title

A Phase 1 Open-Label Dose Escalation and Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of LP-168 in Adult Patients With Relapse or Refractory B-Cell Lymphoma

Overview

This is an open-label, multi-center Phase 1/2 study of oral LP-168 in patients with CLL/SLL and NHL who have failed or are intolerant to standard of care.

Detailed description

This study includes 2 parts: phase 1a (LP-168 monotherapy dose escalation) and phase 1b (LP-168 dose expansion). In phase 1a, patients will be enrolled using an 3+3 design. The starting dose of LP-168 in oral tablet form is 100 mg/day (e.g., 100 mg once daily \[QD\]). Once the MTD and/or RP2D is identified in phase 1a dose escalation, enrollment will continue to phase 1b dose expansion. Cycle length will be 28 days.

Interventions

• Drug LP-168 tablet
  Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily

Primary outcome measures

• Maximum Tolerated Dose (MTD) [Time frame: Up to 24 Months]
• Recommended dose for Phase2 (RP2D) [Time frame: Up to 24 Months]
• To evaluate the safety of LP-168 by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0 [Time frame: Up to 24 Months]

Secondary outcome measures (7)

• Overall Response Rate [Time frame: Up to 24 Months]
• Progression Free Survival [Time frame: Up to 24 Months]
• Duration of Response [Time frame: Up to 24 Months]
• Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of LP-168 [Time frame: Up to 48 hours post dose]
• PK As Assessed By Area Under The Plasma Concentration Time Curve From Time 0 To The Time Of The Last Quantifiable Concentration (AUC0-t) Of LP-168 [Time frame: Up to 48 hours post dose]
• PK As Assessed By Time To Maximum Observed Plasma Concentration (Tmax) Of LP-168 [Time frame: Up to 48 hours post dose]
• PK As Assessed By Terminal Half-life (t1/2) Of LP-168 [Time frame: Up to 48 hours post dose]

Eligibility criteria

Inclusion criteria

• Per 2017 revised WHO lymphoma classification criteria, subject must have either:

Diagnosed with relapsed or refractory DLBCL or FL and require treatment in the opinion of the Investigator and have received 2 lines SOC.

Diagnosed with relapsed or refractory non-Hodgkin's lymphoma associated with B-cell proliferation (such as CLL\\ SLL \\ MCL \\ MZL \\ WM, etc.) in need of treatment in the opinion of the Investigator and have received 1 line SOC.

• Adequate hematologic function.
• Adequate hepatic and renal function.
• Ability to receive study drug therapy orally and willing to receive examinations.
• Willingness of men and women of reproductive potential (defined as following menarche and not postmenopausal \[and 2 years of non-therapy-induced amenorrhea\] or surgically sterile) to observe conventional and effective birth control.

Exclusion criteria

• According to the 2017 revised WHO Lymphoma Classification Criteria, patients diagnosed with the following diseases: Burkitt lymphoma or Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, and post-transplant lymphoproliferative disease(PTLD).
• Prior malignancy (other than the disease under study) within the past 3 years, except for curatively treated basal or squamous cell skin cancer, carcinoma in situ of the cervix or breast cancer.
• Subjects who have received the following treatments within 4 weeks or 5 half-lives before the first dose of LP-168:

Antitumor therapies including myelosuppressive chemotherapy, targeted therapy, biological therapy and/or immunotherapy; Any investigational treatment; Patients who have undergone major surgery, severe trauma or radiotherapy.

• Subjects who have received the following treatments within 2 weeks before the first dose of LP-168:

Steroids or traditional herbal medicine for antitumor purposes; Strong and moderate CYP3A inhibitors and inducers; All drugs that may cause QTc interval prolongation or torsional tachycardia.

• Disease states where clinical manifestations may be difficult to control, including HIV, HBV, HCV, syphilis positive or active bacterial and fungal infections; Disease affects the central nervous system with obvious symptoms; Autoimmune hemolytic anemia or Idiopathic thrombocytopenic purpura. Any gastrointestinal conditions that may severely affect the study drug absorption or pharmacokinetic parameters.
• Subjects who cannot tolerate urine collection, venipuncture, lymph node biopsy, and bone marrow aspiration.

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• Peking University Third Hospital — Beijing
• Beijing Cancer Hospital — Beijing
• Sun Yat-sen University Cancer Center — Guangzhou

Publications

• Lin N, Cai Q, Zhou K, Sun X, Ding K, Zhang L, Jin Z, Jiang M, Peng Z, Li L, Yang W, Zhou M, Shi Y, Wang Z, Liu N, Lou Y, Shen Y, Chen Y, Tan F, Song Y, Zhu J. Rocbrutinib, a Highly Selective Fourth-Generation Covalent and Noncovalent BTK Inhibitor, in R/R Non-GCB DLBCL: Efficacy and Safety from a Phase I Study. Adv Ther. 2026 Jul 24. doi: 10.1007/s12325-026-03711-3. Online ahead of print. PMID 42496861

Identifiers

NCT: NCT04993690 · LP-168-CN101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗