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

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)

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

Study Overview

• Status: Withdrawn
• Conditions: Follicular Lymphoma; Waldenstrom Macroglobulinemia; Lymphoplasmacytic Lymphoma; NHL; DLBCL; Richter Syndrome; CLL/SLL; MCL; MZL
• Intervention / Treatment: Drug: HMPL-760

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 Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• France
  • Alpes Maritimes
    • Nice, Alpes Maritimes, France, 6200
      • Centre Antoine Lacassagne
  • Paris
    • Paris cedex 12, Paris, France, 7551
      • Hopital Saint-Antoine
    • Paris cedex 13, Paris, France, 75651
      • Groupe Hospitalier Pitie-Salpetriere
  • Val De Marne
    • Villejuif cedex, Val De Marne, France, 94805
      • Institut Gustave Roussy
  • Vienne
    • Poitiers, Vienne, France, 86021
      • CHU Poitiers - Hopital la Miletrie
• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital - Ein Kerem
  • Petach-Tikva, Israel, 4941492
    • Rabin Medical Center-Beilinson Campus
  • Ramat Gan, Israel, 5262001
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Roma
    • Lazio, Roma, Italy, 168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Fondazione del Piemonte per l'Oncologia IRCC Candiolo
• Poland
  • Katowice, Poland, 40-519
    • Pratia Onkologia Katowice
  • Legnica, Poland, 59-220
    • Wojewodzki Szpital Specjalistyczny w Legnicy
  • Skórzewo, Poland, 60-185
    • Centrum Medyczne Pratia Poznan
  • Toruń, Poland, 87-100
    • MICS Centrum Medyczne Torun
• Spain
  • Barcelona, Spain, 8003
    • Hospital Del Mar
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28033
    • Md Anderson Cancer Centre
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 8908
      • ICO L'Hospitalet - Hospital Duran i Reynals
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Universitario Quirónsalud Madrid
  • Sevilla
    • Seville, Sevilla, Spain, 41010
      • Hospital Universitario Virgen del Rocio
• United States
  • California
    • Anaheim, California, United States, 92801
      • Innovative Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Clinical Research Center
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company
    • Saint Louis, Missouri, United States, 63110
      • Center for Advanced Medicine
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Med Center. Lab
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance
  • Texas
    • El Paso, Texas, United States, 79915
      • Renovatio Clinical
    • Houston, Texas, United States, 77030
      • Oncology Consultants, P.A.
    • The Woodlands, Texas, United States, 79915
      • Renovatio Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
MTD	To evaluate maximum tolerated dose of HMPL-760 in subjects, if reached	From 1st dose to within 30 days of last dose
RP2D	To determine recommended phase 2 dose of HMPL-760 in subjects	From 1st dose to within 30 days of last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Maximum Plasma Concentration [Cmax]	To determine the maximum observed plasma concentration of HMPL-760	From 1st dose to within 30 days of last dose
Chemokines	To observe blood plasma concentrations of chemokines such as CCL22 and CCL3	From 1st dose to within 30 days of last dose
Phospho-BTK	To observe the whole blood concentrations of phospho-BTK	From 1st dose to within 30 days of last dose

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Study Director: Vijay Jayaprakash, MBBS, PHD, Hutchison Medipharma Limited

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): November 16, 2022
• Study Completion (Actual): November 16, 2022

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Estimate): February 20, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Follicular lymphoma; Diffuse large B-cell lymphoma; Chronic lymphocytic leukemia; Non-Hodgkin lymphoma; Mantle cell lymphoma; Lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia; Marginal zone lymphoma; BTK inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Lymphoma; Lymphoma, Follicular; Waldenstrom Macroglobulinemia
• Other Study ID Numbers: 2021-760-GLOB1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No