A Study of LP-168 in Participants With Relapse or Refractory B-Cell Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I Dose Escalation Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated |
Drug: LP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
|
| Experimental: Phase I Dose Expansion A CLL/SLL patients treated with prior regimens. |
Drug: LP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
|
| Experimental: Phase I Dose Expansion B CLL/SLL patients with no prior therapy. |
Drug: LP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
|
| Experimental: Phase I Dose Expansion C MCL patients treated with prior regimens. |
Drug: LP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
|
| Experimental: Phase I Dose Expansion D WM patients treated with prior regimens. |
Drug: LP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
|
| Experimental: Phase I Dose Expansion E MZL patients treated with prior regimens. |
Drug: LP-168 tablet
Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University Third Hospital | Beijing | Beijing | China | 100089 |
| 2 | Beijing Cancer Hospital | Beijing | Beijing | China | 100142 |
| 3 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Guangzhou Lupeng Pharmaceutical Company LTD.
Investigators
- Study Chair: Jun Zhu, Peking University Cancer Hospital & Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LP-168-CN101