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

NCT ID: NCT05176691

Last Updated: 2023-02-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-15
• Study Completion Date: 2022-11-16

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

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

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

All patients to receive HMPL-760 daily.

Group Type: EXPERIMENTAL

HMPL-760

Intervention Type: DRUG

Administered orally QD for 28-day cycles

Interventions

HMPL-760

Administered orally QD for 28-day cycles

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchmed

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vijay Jayaprakash, MBBS, PHD

Role: STUDY_DIRECTOR

Hutchison Medipharma Limited

Locations

Innovative Clinical Research

Anaheim, California, United States

Emory University Hospital

Atlanta, Georgia, United States

Tulane Cancer Center

New Orleans, Louisiana, United States

Johns Hopkins Clinical Research Center

Baltimore, Maryland, United States

AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company

Kansas City, Missouri, United States

Center For Advanced Medicine

St Louis, Missouri, United States

Summit Medical Group

Florham Park, New Jersey, United States

New York University Langone Med Center. Lab

New York, New York, United States

Clinical Research Alliance

Westbury, New York, United States

Renovatio Clinical

El Paso, Texas, United States

Oncology Consultants, P.A.

Houston, Texas, United States

Renovatio Clinical

The Woodlands, Texas, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Centre Antoine Lacassagne

Nice, Alpes Maritimes, France

Hôpital Saint-Antoine

Paris, Paris, France

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, France

Institut Gustave Roussy

Villejuif, Val De Marne, France

CHU Poitiers - Hôpital la Milétrie

Poitiers, Vienne, France

Hadassah University Hospital - Ein Kerem

Jerusalem, , Israel

Rabin Medical Center-Beilinson Campus

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Lazio, Roma, Italy

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, Italy

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, , Italy

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Pratia Onkologia Katowice

Katowice, , Poland

Wojewodzki Szpital Specjalistyczny w Legnicy

Legnica, , Poland

Centrum Medyczne Pratia Poznan

Skórzewo, , Poland

MICS Centrum Medyczne Torun

Torun, , Poland

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital Universitario Virgen del Rocio

Seville, Sevilla, Spain

Hospital del Mar

Barcelona, , Spain

MD Anderson Cancer Centre

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Countries

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

Other Identifiers

2021-760-GLOB1

Identifier Type: -

Identifier Source: org_study_id