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

Study Overview
=================
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.

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

Conditions
-----------------
B-cell Lymphoma

Intervention / Treatment
-----------------
* Drug: LP-168 tablet


Participation Criteria
=================
Eligibility 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I Dose Escalation<br>Dose Escalation and determination of MTD; multiple dose levels of LP-168 to be evaluated | Drug: LP-168 tablet<br>* Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily<br>|
| Experimental: Phase I Dose Expansion A<br>CLL/SLL patients treated with prior regimens. | Drug: LP-168 tablet<br>* Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily<br>|
| Experimental: Phase I Dose Expansion B<br>CLL/SLL patients with no prior therapy. | Drug: LP-168 tablet<br>* Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily<br>|
| Experimental: Phase I Dose Expansion C<br>MCL patients treated with prior regimens. | Drug: LP-168 tablet<br>* Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily<br>|
| Experimental: Phase I Dose Expansion D<br>WM patients treated with prior regimens. | Drug: LP-168 tablet<br>* Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily<br>|
| Experimental: Phase I Dose Expansion E<br>MZL patients treated with prior regimens. | Drug: LP-168 tablet<br>* Subjects to take LP-168 orally with 240mL water, without food, Once daily or twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 |