Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas

NCT03786926 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 2018-689-00US1
• Study Type: interventional
• Target: 53
• Locations: 6 countries
• Sites: 27

Brief Summary

An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas

Conditions

Lymphoma

Keywords

CLL; SLL; FL; MZL; LPL; WM; MCL; PTCL; CBCL

Outcome Measures

Primary Outcomes (3)

• Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)

  A DLT was defined as the occurrence of any of the following treatment-emergent adverse events (TEAEs) during the DLT assessment window, unless equivocally due to underlying malignancy or an extraneous cause. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: non-hematologic toxicity: all non-hematologic TEAEs of grade 3 or greater with the exception of grade 3 nausea or vomiting that could be controlled by supportive therapy; hematologic toxicity: grade 4 neutropenia \>5 days, grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding event or requiring platelet transfusion, grade \>=3 febrile neutropenia (defined as absolute neutrophil count \[ANC\] \<1000/cubic millimeter {mm\^3} with a single temperature \>38.3 degree Celsius \[°C\] or a sustained temperature of \>=38°C for more than 1 hour), grade 4 anemia not explained by underlying disease; any TEAE that required a dose delay of \>=15 days; any case of Hy's Law.

  From the first dose of study drug (Day 1) up to Day 28 of Cycle 1 (each cycle is 28 days)

• Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events (TEAEs), Treatment Related Treatment-Emergent Adverse Events (TRAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment Related Serious Adverse Events (TRSAEs)

  An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. An SAE was an AE that resulted in any of the following: was fatal, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in a neonate/infant born to a female patient or female partner of a male patient exposed to the study drug, or was considered a significant medical event by the investigator. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs and SAEs were defined as AEs and SAEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.

  From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 34 months

• Dose Expansion Stage: Number of Patients With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events

  An AE was any untoward medical occurrence in a clinical investigation patient administered a study drug, regardless of causal attribution. TEAEs were defined as AEs with onset date on or after the first dose of study drug and no later than 30 days after the date of last study drug administration or start of a new study drug of anti-neoplasm therapy, whichever was earlier. Treatment related AEs were defined as AEs collected later than 30 days after the last study drug date or start of a new study drug of anti-neoplasm therapy.

  From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 27 months

Secondary Outcomes (10)

• Dose Escalation and Dose Expansion Stages: Objective Response Rate (ORR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months

• Dose Escalation and Dose Expansion Stages: Time to Response (TTR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months

• Dose Escalation and Dose Expansion Stages: Duration of Response (DOR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7days) thereafter, up to a maximum of 58 months

• Dose Escalation and Dose Expansion Stages: Clinical Benefit Rate (CBR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months

• Dose Escalation and Dose Expansion Stages: Progression-Free Survival (PFS)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter, up to a maximum of 58 months

Study Arms (1)

Treatment

EXPERIMENTAL

All patients take HMPL-689 taken daily

Drug: HMPL-689

Interventions

HMPL-689 DRUG

HMPL-689 is a PI3Kδ inhibitor

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (ECOG) performance status of 0 or 1;
• Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade 1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);
• Patients with relapsed or refractory NHL for whom:
• Standard of care treatment options no longer exist (Stage 1 only);
• Standard of care treatment options no longer exist with the exception of PI3K-delta inhibitors (Stage 2 only);
• Expected survival of more than 24 weeks.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Primary central nervous system (CNS) lymphoma;
• Any of the following laboratory abnormalities Absolute neutrophil count; \<1.0×10\^9/L, Hemoglobin \<80 g/L Platelets \<50 ×10\^9/L
• Inadequate organ function, defined by the following:
• Total bilirubin ≥1.5 times the upper limit of normal (× ULN);
• AST or ALT \> 2.5 × ULN;
• Estimated creatinine clearance (CrCl) per Cockcroft-Gault;
• Dose Escalation stage of trial (Stage 1) - CrCl \< 40 mL/min;
• Dose Expansion stage of trial (Stage 2) - CrCl \<30 mL/min;
• International normalized ratio (INR) \> 1.5 × ULN, activated partial thromboplastin time (aPTT) \> 1.5 × ULN;
• Serum amylase or lipase \> ULN at screening or known medical history of serum amylase or lipase \> ULN;
• Patients with presence of second primary malignant tumors within the last 2 years;
• Clinically significant history of liver disease;
• Prior treatment with any PI3Kδ inhibitors;
• Any prior use of the following: cancer therapy within 3 weeks of study treatment, GCSF within 7 days of screening, steroid therapy or targeted anti-neoplastic intent within 7 days of treatment, any use of strong CYP3A4 inducers within 2 weeks prior to initiation of study treatment, prior autologous transplant within 6 months of study treatment, prior allogenic stem cell transplant within 6 months of study treatment;

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (27)

Innovative Clinical Research Institute

Anaheim, California, 92801, United States

Location

Pacific Cancer Medical Center

Anaheim, California, 92801, United States

Location

Ventura County Hematology-Oncology Specialists

Oxnard, California, 93030, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Clinical Research Alliance, Inc

Westbury, New York, 11590, United States

Location

Levine Cancer Institute- Atrium Health

Charlotte, North Carolina, 28204, United States

Location

Baylor Scott and White Research Institute

Dallas, Texas, 75246, United States

Location

Renovatio Clinical

Houston, Texas, 77339, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Medical Oncology Associates, P.S.

Spokane, Washington, 99208, United States

Location

Helsingin yliopistollinen keskussairaala

Helsinki, 00029, Finland

Location

Tampereen yliopistollinen sairaala

Tampere, 33520, Finland

Location

Hopital Henri Mondor

Créteil, Val De Marne, 94010, France

Location

CHU de Nantes - Hotel Dieu

Nantes, 44000, France

Location

CHU de Bordeaux - Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

KO-MED Centra Kliniczne

Biała Podlaska, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Location

BioResearch Group Sp. Z. o. o.

Krakow, Poland

Location

NASZ LEKARZ Osrodek Badan Klinicznych

Torun, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego

Wroclaw, 50-566, Poland

Location

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Barcelona, Spain

Location

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, Spain

Location

Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study was terminated based on strategic evaluation of the clinical development of HMPL-689 in the United States, Europe, and Australia with no safety concerns.

Results Point of Contact

• Title: Chao Pan
• Organization: HUTCHMED Limited

chaop@hutch-med.com

(+86)15215192478

Study Officials

• Claudia Huang

  Hutchmed Limited

  STUDY DIRECTOR

• Nilanjan Ghosh, MD

  Atrium Health Levine Cancer Institute

  PRINCIPAL INVESTIGATOR

• Jonathan B Cohen, MD

  Emory Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 26, 2018
• Study Start: August 26, 2019
• Primary Completion: June 26, 2024
• Study Completion: June 26, 2024
• Last Updated: June 26, 2025
• Results First Posted: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); FI (2); IT (2); PL (5); US (10); FR (3)