HMPL-760 Safety and Tolerability Study in Patients With Previously Treated CLL/SLL or NHL

Sponsor

Hutchison Medipharma Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05176691

Collaborator

(none)

168

Enrollment

Locations

Arm

44.5

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL

Condition or Disease	Intervention/Treatment	Phase
CLL/SLL NHL MCL MZL Lymphoplasmacytic Lymphoma Waldenstrom Macroglobulinemia Follicular Lymphoma DLBCL Richter Syndrome	Drug: HMPL-760	Phase 1

Detailed Description

HMPL-760 is a highly potent, selective, and reversible inhibitor against BTK, which would be studied in B-cell malignancy carrying either BTK(WT) or BTK(C481S).

This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL

The study consists of 2 parts:

Part 1- Dose Escalation to determine MTD and/or RP2D of HMPL-760

Part 2- Dose Expansion to characterize the safety and tolerability of HMPL-760

Study Design

Study Type:

Interventional

Anticipated Enrollment :

168 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL)

Actual Study Start Date :

Feb 15, 2022

Anticipated Primary Completion Date :

Apr 30, 2025

Anticipated Study Completion Date :

Oct 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment All patients to receive HMPL-760 daily.	Drug: HMPL-760 Administered orally QD for 28-day cycles

Arm

Intervention/Treatment

Experimental: Treatment

All patients to receive HMPL-760 daily.

Drug: HMPL-760

Administered orally QD for 28-day cycles

Outcome Measures

Primary Outcome Measures

Incidence of DLTs [Up to 28 days after first dose of study drug]
Adverse event (AE) that meets protocol defined DLT criteria during dose escalation
Incidence of AEs/SAEs [From 1st dose to within 30 days of last dose]
Any untoward medical occurrence associated with the use of study drug
MTD [From 1st dose to within 30 days of last dose]
To evaluate maximum tolerated dose of HMPL-760 in subjects, if reached
RP2D [From 1st dose to within 30 days of last dose]
To determine recommended phase 2 dose of HMPL-760 in subjects

Secondary Outcome Measures

Objective Response Rate (ORR) [From 1st dose of study drug to the time of progressive disease, assessed up to 36 months]
ORR is defined as the proportion of subjects achieving partial response and better response during the study
Duration of Response (DoR) [From first dose of study drug to the time of progressive disease, assessed up to 36 months]
DoR is defined as the time between the initial response to therapy and subsequent disease progression or relapse.
Clinical Benefit Rate (CBR) [From 1st dose of study drug to the time of progressive disease, assessed up to 36 months]
CBR is defined as the proportion of subjects achieving objective response or stable disease
Progression-free Survival (PFS) [From 1st dose of study drug to the time of progressive disease, assessed up to 36 months]
PFS is defined as survival without progression of the disease
Maximum Plasma Concentration [Cmax] [From 1st dose to within 30 days of last dose]
To determine the maximum observed plasma concentration of HMPL-760
Chemokines [From 1st dose to within 30 days of last dose]
To observe blood plasma concentrations of chemokines such as CCL22 and CCL3
Phospho-BTK [From 1st dose to within 30 days of last dose]
To observe the whole blood concentrations of phospho-BTK

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ECOG performance status of 0 or 1;
Histologically confirmed NHL or CLL with disease progression or intolerance to either ≥2 prior regimens. Patients with CLL/SLL and indolent NHL must meet criteria for systemic therapy. Patients with gastric extranodal MZL who are H. pylori positive must have failed H. pylori eradication therapy.
Availability of tumor sample: This may be an archival tissue sample obtained after most recent therapy or a fresh biopsy; if tumor sample is not available for patients in dose escalation, the Sponsor may waive the requirement after discussion.
Dose expansion stage only: Patients must have been treated with 1 prior regimen containing a BTK inhibitor in cohorts 1 to 5;
Expected survival of more than 24 weeks as determined by the Investigator.

Exclusion Criteria:

Patients with primary central nervous system lymphoma.
Any of the following laboratory abnormalities:
Absolute neutrophil count (ANC) <0.75×109/L
Hemoglobin <8 mg/L
Platelets <50×109/L
Note: In the dose expansion stage, patients with cell counts below the thresholds listed above may be considered eligible if there is documented bone marrow infiltration and Sponsor approval
Inadequate organ function
International normalized ratio (INR) >1.5×ULN, activated partial thromboplastin time (aPTT) >1.5×ULN
Patients requiring anticoagulation therapy (except vitamin K antagonists [ie, warfarin]) but with a stable INR within the recommended range according to the local guideline are eligible.
Patients with presence of second primary malignant tumors within the last 2 years, with the exception of the following:
Basal cell carcinoma of the skin
Squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Clinically significant history of liver disease, including cirrhosis or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV).
Cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine, or radiotherapy within 3 weeks prior to initiation of study treatment. For oral targeted therapies, a washout period of 5 half-lives of the agent (minimum 3 days) prior to the initiation of study treatment can be used.
Any granulocyte colony-stimulating factor treatment/blood transfusion within 7 days before the screening hematology test.
Prior use of any drug that is a strong inducer or inhibitor of CYP3A4 within 2 weeks prior to initiation of study treatment.
Prior use of proton pump inhibitors (PPIs) within 5 days of study treatment
Any transplant within 100 days prior to initiation of study treatment
Clinically significant active infection or with an unexplained fever.
Treatment within a clinical study of an investigational agent or using an investigational device within 3 weeks prior to initiation of the current study treatment.
AEs from prior antineoplastic therapy that have not resolved to grade <1
Pregnant (positive urine or serum beta human chorionic gonadotropin test) or lactating women.
New Your Heart Association (NYHA) class II or greater congestive heart failure.

NOTE: Only key inclusion/exclusion criteria are listed. Full details are in the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Hospital	Atlanta	Georgia	United States	30322
2	Johns Hopkins Clinical Research Center	Baltimore	Maryland	United States	21287
3	Center For Advanced Medicine	Saint Louis	Missouri	United States	63110
4	Summit Medical Group	Florham Park	New Jersey	United States	07932