Phase I Study of HRS-3738 in Recurrent and Refractory Non-Hodgkin's Lymphoma and Multiple Myeloma

Study Overview
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Brief Summary
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This study is an open-label, multicenter Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of HRS-3738 in patients with recurrent and refractory Non-Hodgkin's lymphoma and multiple myeloma.

Official Title
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Phase I Study of HRS-3738 in Recurrent and Refractory Non-Hodgkin's Lymphoma and Multiple Myeloma

Conditions
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Recurrent and Refractory Non-Hodgkin's Lymphoma and Multiple Myeloma

Intervention / Treatment
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* Drug: HRS-3738


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active multiple myeloma in accordance with IMWG criteria，or histopathologically and immunohistochemically confirmed non-Hodgkin's lymphoma in accordance with the 2016 WHO Classification of lymphoid neoplasias. Recurred or did not alleviate after the previous treatment. Have at least one measurable lesion. With a life expectancy of ≥3 months. Male or female ≥ 18 years old. ECOG performance status of 0-1. Subjects must voluntarily agree to participate in the trial and sign a written informed consent form. Exclusion Criteria: Amyloidosis, plasma cell leukemia. Corrected serum calcium>3.4mmol/L(13.5mg/dl). Presence of metastasis to central nervous system. Treatment of other investigational products. Major surgical therapy within 28 days prior to the date of signature of informed consent form, or expected major surgery during the study. Known history of hypersensitivity to any components of HRS-3738. Other factors that may affect the study results or lead to forced termination of the study early as judged by investigators.

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
Interventional Model Description: Single arm study of HRS-3738
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRS-3738<br>In dose Escalation: HRS-3738 will be taken in oral. Seven dose levels are preset. In dose Expansion: 2 to 3 dose cohorts will be selected for dose expansion stage. In indication Expansion: Indications will be selected to evaluate preliminary efficacy. | Drug: HRS-3738<br>* HRS-3738 will be administrated per dose level in which the patients are assigned.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | Incidence and category of dose limiting toxicities (DLTs) during the first 28-day cycle of HRS-3738 treatment. | From Day 1 to Day 28 | 
| RP2D | RP2D will be determined on the basis of evaluation on safety, PK, efficacy data in dose escalation and dose expansion stages. | From Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoints: adverse events(AEs), serious adverse events（SAEs） | Assess safety and tolerability of HRS-3738 by way of adverse events (CTCAE v5.0). | From Day 1 to 30 days after last dose. | 
| Efficacy endpoints: Overall response rate (ORR) | Evaluated using Lugano 2014 criteria and IMWG criteria. | From Day 1 to 30 days after last dose. | 
| Efficacy endpoints: Best of response (BOR) | Evaluated using Lugano 2014 criteria and IMWG criteria | From Day 1 to 30 days after last dose | 
| Efficacy endpoints: time to response (TTR) | Evaluated using Lugano 2014 criteria and IMWG criteria. | From Day 1 to 30 days after last dose. | 
| Efficacy endpoints: Duration of response (DoR) | Evaluated using Lugano 2014 criteria and IMWG criteria | From Day 1 to 30 days after last dose | 
| Efficacy endpoints: Progression-free survival (PFS) | Evaluated using Lugano 2014 criteria and IMWG criteria | From Day 1 to 30 days after last dose | 
| Efficacy endpoints: overall survival (OS). | Evaluated using Lugano 2014 criteria and IMWG criteria. | From Day 1 to 30 days after last dose. | 
| Cmax | Maximal plasma concentration | From Day 1 to 30 days after last dose | 
| Tmax | Time to Cmax | From Day 1 to 30 days after last dose | 
| AUC | Area under the plasma concentration-time curve | From Day 1 to 30 days after last dose | 
| t1/2 | Terminal-phase elimination half-life | From Day 1 to 30 days after last dose | 
| Vz/F | Apparent volume of distribution during terminal phase after non-intravenous administration | From Day 1 to 30 days after last dose | 
| CL/F | Apparent total clearance of the drug from plasma after oral administration. | From Day 1 to 30 days after last dose |