Clinical trial NCT05176691: HMPL-760 Safety and Tolerability Study in Patients With Previously Treated CLL/SLL or NHL
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: CLL/SLL
NHL
MCL
MZL
Lymphoplasmacytic Lymphoma
Waldenstrom Macroglobulinemia
Follicular Lymphoma
DLBCL
Richter Syndrome
Keywords: Lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia
Chronic lymphocytic leukemia
Non-Hodgkin lymphoma
Mantle cell lymphoma
Marginal zone lymphoma
Follicular lymphoma
Diffuse large B-cell lymphoma
BTK inhibitor
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2022-01-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

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

Primary outcomes:
measure: Incidence of DLTs
timeFrame: Up to 28 days after first dose of study drug
measure: Incidence of AEs/SAEs
timeFrame: From 1st dose to within 30 days of last dose
measure: MTD
timeFrame: From 1st dose to within 30 days of last dose
measure: RP2D
timeFrame: From 1st dose to within 30 days of last dose
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
measure: Duration of Response (DoR)
timeFrame: From first dose of study drug to the time of progressive disease, assessed up to 36 months
measure: Clinical Benefit Rate (CBR)
timeFrame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
measure: Progression-free Survival (PFS)
timeFrame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months
measure: Maximum Plasma Concentration [Cmax]
timeFrame: From 1st dose to within 30 days of last dose
measure: Chemokines
timeFrame: From 1st dose to within 30 days of last dose
measure: Phospho-BTK
timeFrame: From 1st dose to within 30 days of last dose
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Innovative Clinical Research
state: California
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Clinical Research Center
state: Maryland
city: Kansas City
country: United States
facility: AMR Kansas City, Formerly Center for Pharmaceutical Research, an AMR company
state: Missouri
city: Saint Louis
country: United States
facility: Center For Advanced Medicine
state: Missouri
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: New York
country: United States
facility: New York University Langone Med Center. Lab
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance
state: New York
city: El Paso
country: United States
facility: Renovatio Clinical
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, P.A.
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Nice
country: France
facility: Centre Antoine Lacassagne
state: Alpes Maritimes
city: Paris cedex 12
country: France
facility: Hôpital Saint-Antoine
state: Paris
city: Paris cedex 13
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
state: Paris
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
state: Val De Marne
city: Poitiers
country: France
facility: CHU Poitiers - Hôpital la Milétrie
state: Vienne
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
city: Petach-Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Lazio
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Roma
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia IRCC Candiolo
state: Torino
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Legnica
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Legnicy
city: Skórzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Toruń
country: Poland
facility: MICS Centrum Medyczne Torun
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
state: Barcelona
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Sevilla
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
Study officials:
affiliation: Hutchison Medipharma Limited
name: Vijay Jayaprakash, MBBS, PHD
role: STUDY_DIRECTOR
References: