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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase I Dose Escalation | Experimental | Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated |
|
| Phase I Dose Expansion A | Experimental | CLL/SLL patients treated with prior regimens. |
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| Phase I Dose Expansion B | Experimental | CLL/SLL patients with no prior therapy. |
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| Phase I Dose Expansion C | Experimental | MCL patients treated with prior regimens. |
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| Phase I Dose Expansion D | Experimental | WM patients treated with prior regimens. |
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| Phase I Dose Expansion E | Experimental | MZL patients treated with prior regimens. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LP-168 tablet | Drug | Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Phase 1a | Up to 24 Months |
| Recommended dose for Phase2 (RP2D) | Phase Ia/Ib | 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 | Phase Ia/Ib | Up to 24 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate | To assess the preliminary anti-tumor activity of LP-168 based on overall response rate (ORR) as assessed by investigator and IRC. | Up to 24 Months |
| Progression Free Survival |
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Key Inclusion Criteria:
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.
Key Exclusion Criteria:
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.
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jun Zhu, MD, PhD | Contact | +86-010-88196596 | zj@bjcancer.org | |
| Yuqin Song, MD, PhD | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Jun Zhu | Peking University Cancer Hospital & Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Recruiting | Beijing | Beijing Municipality | 100089 | China |
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| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated
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|
To assess the preliminary anti-tumor activity of LP-168 based on Progression free survival (PFS) as assessed by the Investigator and IRC
| Up to 24 Months |
| Duration of Response | To assess the preliminary anti-tumor activity of LP-168 based on Duration of response (DOR) as assessed by the Investigator and IRC. | Up to 24 Months |
| Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of LP-168 | Phase Ia/Ib | 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 | Phase Ia/Ib | Up to 48 hours post dose |
| PK As Assessed By Time To Maximum Observed Plasma Concentration (Tmax) Of LP-168 | Phase Ia/Ib | Up to 48 hours post dose |
| PK As Assessed By Terminal Half-life (t1/2) Of LP-168 | Phase Ia/Ib | Up to 48 hours post dose |
| Beijing Cancer Hospital | Recruiting | Beijing | Beijing Municipality | 100142 | China |
|
| Sun Yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510060 | China |
|
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |