B-cell Lymphoma
Conditions
Brief summary
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
DRUGLP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
Sponsors
Guangzhou Lupeng Pharmaceutical Company LTD.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key 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. Key
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Up to 24 Months | Phase 1a |
| Recommended dose for Phase2 (RP2D) | Up to 24 Months | Phase Ia/Ib |
| To evaluate the safety of LP-168 by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0 | Up to 24 Months | Phase Ia/Ib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Up to 24 Months | To assess the preliminary anti-tumor activity of LP-168 based on overall response rate (ORR) as assessed by investigator and IRC. |
| Progression Free Survival | Up to 24 Months | To assess the preliminary anti-tumor activity of LP-168 based on Progression free survival (PFS) as assessed by the Investigator and IRC |
| Duration of Response | Up to 24 Months | To assess the preliminary anti-tumor activity of LP-168 based on Duration of response (DOR) as assessed by the Investigator and IRC. |
| Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of LP-168 | Up to 48 hours post dose | Phase Ia/Ib |
| 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 | Up to 48 hours post dose | Phase Ia/Ib |
| PK As Assessed By Time To Maximum Observed Plasma Concentration (Tmax) Of LP-168 | Up to 48 hours post dose | Phase Ia/Ib |
| PK As Assessed By Terminal Half-life (t1/2) Of LP-168 | Up to 48 hours post dose | Phase Ia/Ib |
Countries
China
Contacts
CONTACTJun Zhu, MD, PhD
CONTACTYuqin Song, MD, PhD
STUDY_CHAIRJun Zhu
Peking University Cancer Hospital & Institute
Outcome results
None listed