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

Follicular Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05176691
• Other study ID #: 2021-760-GLOB1
• Status: Withdrawn
• Phase: Phase 1
• Start date: February 15, 2022
• Est. completion date: November 16, 2022

Study information

• Verified date: February 2023
• Source: Hutchmed
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 16, 2022
• Est. primary completion date: November 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• CLL/SLL
• DLBCL
• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular
• Lymphoplasmacytic Lymphoma
• MCL
• MZL
• NHL
• Richter Syndrome
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• HMPL-760
Administered orally QD for 28-day cycles

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
France	Centre Antoine Lacassagne	Nice	Alpes Maritimes
France	Hôpital Saint-Antoine	Paris cedex 12	Paris
France	Groupe Hospitalier Pitie-Salpetriere	Paris cedex 13	Paris
France	CHU Poitiers - Hôpital la Milétrie	Poitiers	Vienne
France	Institut Gustave Roussy	Villejuif cedex	Val De Marne
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Rabin Medical Center-Beilinson Campus	Petach-Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS	Bologna
Italy	Fondazione del Piemonte per l'Oncologia IRCC Candiolo	Candiolo	Torino
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Lazio	Roma
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Poland	Pratia Onkologia Katowice	Katowice
Poland	Wojewodzki Szpital Specjalistyczny w Legnicy	Legnica
Poland	Centrum Medyczne Pratia Poznan	Skórzewo
Poland	MICS Centrum Medyczne Torun	Torun
Spain	Hospital del Mar	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Virgen del Rocio	Seville	Sevilla
United States	Innovative Clinical Research	Anaheim	California
United States	Emory University Hospital	Atlanta	Georgia
United States	Johns Hopkins Clinical Research Center	Baltimore	Maryland
United States	Renovatio Clinical	El Paso	Texas
United States	Summit Medical Group	Florham Park	New Jersey
United States	Oncology Consultants, P.A.	Houston	Texas
United States	AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company	Kansas City	Missouri
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	New York University Langone Med Center. Lab	New York	New York
United States	Center For Advanced Medicine	Saint Louis	Missouri
United States	Renovatio Clinical	The Woodlands	Texas
United States	Clinical Research Alliance	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hutchmed

Countries where clinical trial is conducted

United States,  Australia,  France,  Israel,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of DLTs	Adverse event (AE) that meets protocol defined DLT criteria during dose escalation	Up to 28 days after first dose of study drug
Primary	Incidence of AEs/SAEs	Any untoward medical occurrence associated with the use of study drug	From 1st dose to within 30 days of last dose
Primary	MTD	To evaluate maximum tolerated dose of HMPL-760 in subjects, if reached	From 1st dose to within 30 days of last dose
Primary	RP2D	To determine recommended phase 2 dose of HMPL-760 in subjects	From 1st dose to within 30 days of last dose
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of subjects achieving partial response and better response during the study	From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Secondary	Duration of Response (DoR)	DoR is defined as the time between the initial response to therapy and subsequent disease progression or relapse.	From first dose of study drug to the time of progressive disease, assessed up to 36 months
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as the proportion of subjects achieving objective response or stable disease	From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Secondary	Progression-free Survival (PFS)	PFS is defined as survival without progression of the disease	From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
Secondary	Maximum Plasma Concentration [Cmax]	To determine the maximum observed plasma concentration of HMPL-760	From 1st dose to within 30 days of last dose
Secondary	Chemokines	To observe blood plasma concentrations of chemokines such as CCL22 and CCL3	From 1st dose to within 30 days of last dose
Secondary	Phospho-BTK	To observe the whole blood concentrations of phospho-BTK	From 1st dose to within 30 days of last dose