A Study of LP-168 in Participants with Relapse or Refractory B-Cell Lymphoma
- Conditions
- B-cell Lymphoma
- Interventions
- Drug: LP-168 tablet
- Registration Number
- NCT04993690
- Lead Sponsor
- Guangzhou Lupeng Pharmaceutical Company LTD.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase I Dose Escalation LP-168 tablet Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated Phase I Dose Expansion A LP-168 tablet CLL/SLL patients treated with prior regimens. Phase I Dose Expansion B LP-168 tablet CLL/SLL patients with no prior therapy. Phase I Dose Expansion C LP-168 tablet MCL patients treated with prior regimens. Phase I Dose Expansion D LP-168 tablet WM patients treated with prior regimens. Phase I Dose Expansion E LP-168 tablet MZL patients treated with prior regimens.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
PK As Assessed By Terminal Half-life (t1/2) Of LP-168 Up to 48 hours post dose Phase Ia/Ib
Trial Locations
- Locations (3)
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China