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

Study Overview
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Brief Summary
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This is an open-label, single arm, multi-center Phase 2 study of oral LP-168 in patients with mantle cell lymphoma who are failed or relapsed after remission or intolerated to Bruton's tyrosine kinase (BTK) inhibitor.

Official Title
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An Open Label, Single Arm, Multicenter Phase II Study of the Efficacy and Safety of LP-168 Monotherapy for Recurrent or Refractory Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma (MCL)

Intervention / Treatment
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* Drug: LP-168


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Per 2017 revised WHO lymphoma classification criteria, subject must have diagnosed with MCL. At least one measurable lesion. Subjects who have previously received the treatment regimen containing anti-CD20 and at least one BTKi treatment failed or relapsed after remission or intolerated; Or Subjects who have previously received BTK inhibitors treatment failed or relapsed after remission or intolerated, and are not suitable for treatment with anti-CD20. ECOG≤2. Adequate hematologic function. Adequate hepatic and renal function. 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. Exclusion Criteria: Received non-covalent BTK inhibitor treatment. 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. Any gastrointestinal conditions that may severely affect the study drug absorption or pharmacokinetic parameters.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LP-168<br>Subjects who have previously received BTK inhibitors treatment failed or relapsed after remission or intolerated | Drug: LP-168<br>* Subjects to take LP-168 orally with 240mL water, without food, Once daily.The treatment will continue until progressive disease, unacceptable toxicity, etc.<br>* Other names: NWP-775;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To assess the anti-tumor activity of LP-168 based on overall response rate (ORR) as assessed by Independent Reading Committee (IRC). | Up to 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To assess the anti-tumor activity of LP-168 based on overall response rate (ORR) as assessed by investigator. | Up to 24 Months | 
| Complete remission rate | To assess the preliminary anti-tumor activity of LP-168 based on complete remission rate (CR) 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 investigator and IRC. | Measured from the date of first dose of study drug to the date of earliest disease progression or death or last visit, and assessed up to 24 months. | 
| Overall survival | To assess the preliminary anti-tumor activity of LP-168 based on Overall survival (OS) as assessed by investigator and IRC. | Measured from the date of date of first dose to the date of death or last visit, and for up to 5 years after the last subject is enrolled. | 
| Duration of Response (DOR) | To assess the preliminary anti-tumor activity of LP-168 based on Duration of response (DOR) as assessed by the Investigator and IRC. | Measured from the date of the first remission to the date of earliest disease progression or death, and assessed up to 24 months. | 
| Time to Response (TTR) | To assess the preliminary anti-tumor activity of LP-168 based on Time to response (TTR) as assessed by the Investigator and IRC. | Measured from the date of the first dose of study drug to the date of earliest response, and assessed up to 6 months. | 
| Safety Assessment | To evaluate the safety of LP-168 by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0 | From first dose of study drug to 28 days after last dose of study drug | 
| Maximum Observed Plasma Concentration (Cmax) | Pharmacokinetics (PK) As Assessed By Maximum Observed Plasma Concentration (Cmax) Of LP-168 | Up to 24 hours post dose | 
| Area Under The Plasma Concentration Time Curve From Time 0 To The Time Of The Last Quantifiable Concentration (AUC0-t) | 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 24 hours post dose | 
| Maximum Observed Plasma Concentration (Tmax) | PK As Assessed By Time To Maximum Observed Plasma Concentration (Tmax) Of LP-168 | Up to 24 hours post dose | 
| Half-life period (T1/2) | PK As Assessed By Time To Half-life period (T1/2) Of LP-168 | Up to 24 hours post dose | 
| Quality of life (QoL) | Quality of life Assessed By the European Organization for Research and Treatment of Cancer core quality of life (EORTC QLQ-C30) questionnaire (The total score ranges from 30 to126, Items 29 and 30 are scored from 1 to 7 points, and other items are scored from 1 to 4 points. Except for items 29 and 30, the higher value, the worse QoL.) | Up to 24 Months |