A Study of Tazemetostat in Combination With HMPL-689 in Patients With Relapsed/Refractory Lymphoma

NCT05713110 | Completed Phase 2 DMC

• 1 other identifier: 2021-TAZ-00CH2
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

A phase II clinical study of tazemetostat combined with HMPL-689 in patients with R/R lymphoma. The study includes 2 phases: dose escalation phase (phase IIa) and expansion phase (phase IIb).

Conditions

Relapsed/Refractory Lymphoma

Outcome Measures

Primary Outcomes (5)

• Dose Escalation Phase (Phase IIa):To evaluate the safety, tolerability, and determine the maximum tolerated dose (MTD) and/or RP2D of Tazemetostat in combination with HMPL-689 in patients with R/R lymphoma

  Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period

  from Cycle 1 Day 1 up to Cycle 1 Day 28 (each cycle is 28 days)

• Dose Expansion Phase (Phase IIb):To evaluate the ORR of Tazemetostat in combination with HMPL-689 in patients with lymphoma

  Percentage of patients with Complete Response(CR) or Partial Response(PR) as the best response evaluated in accordance with Lugano2014

  from Cycle 1 Day 1 to PFS (each cycle is 28 days)

• Dose Expansion Phase (Phase IIb):To evaluate the DCR of Tazemetostat in combination with HMPL-689 in patients with lymphoma

  the proportion of patients with CR or PR or stable disease (SD) as the best response with Lugano2014

  from Cycle 1 Day 1 to PFS (each cycle is 28 days)

• Dose Expansion Phase (Phase IIb):To evaluate the DOR of Tazemetostat in combination with HMPL-689 in patients with lymphoma

  as the time from the first appearance of CR or PR to PD or death for any reason (whichever comes first), in the patients with objective response with Lugano2014)

  from Cycle 1 Day 1 to PFS (each cycle is 28 days)

• Dose Expansion Phase (Phase IIb):To evaluate the PFS of Tazemetostat in combination with HMPL-689 in patients with lymphoma

  the proportion of patients with CR or PR or stable disease (SD) as the best response with Lugano2014

  from Cycle 1 Day 1 to PFS (each cycle is 28 days)

Secondary Outcomes (18)

• Dose Escalation Phase (Phase IIa):Objective Response Rate (ORR)

  From baseline to final assessment at end of safety follow-up visit(through study completion, an average of 2 years)

• Dose Escalation Phase (Phase IIa)-Complete Response Rate (CR rate)

  From baseline to final assessment at end of safety follow-up visit(through study completion, an average of 2 years)

• Dose Escalation Phase (Phase IIa)-Disease control rate (DCR)

  From baseline to final assessment at end of safety follow-up visit(through study completion, an average of 2 years)

• Dose Escalation Phase (Phase IIa)-Duration of response (DoR)

  From baseline to final assessment at end of safety follow-up visit(through study completion, an average of 2 years)

• Dose Escalation Phase (Phase IIa)-Time to response (TTR)

  From baseline to final assessment at end of safety follow-up visit(through study completion, an average of 2 years)

Study Arms (1)

tazemetostat combined with HMP689 open-label treatment arm

EXPERIMENTAL

Dose Escalation Phase (Phase IIa): patients with relapsed or refractory lymphoma who have failed standard treatment and have no standard treatment options Dose Expansion Phase (Phase IIb): Cohort 1 (DLBCL, FL 3b): Histologically confirmed DLBCL, FL 3b (including primary mediastinal B-cell lymphoma) with relapsed/refractory disease ； Cohort 2 (FL) patients with histologically confirmed R/R FL (Grade 1, 2, 3a)； Cohort 3 (MCL): Patients with R/R MCL who had prior therapies ； Cohort 4 (PTCL): Patients with histologically confirmed R/R PTCL who have failed or cannot tolerate standard therapy

Drug: tazemetostat; Drug: HMPL-689

Interventions

tazemetostat DRUG

Dose Escalation Phase (Phase IIa): Tazemetostat (800 mg BID orally) in a therapeutic cycle of 28 days; Dose Expansion Phase (Phase IIb): Tazemetostat (800 mg BID orally) in a therapeutic cycle of 28 days

tazemetostat combined with HMP689 open-label treatment arm

HMPL-689 DRUG

Dose Escalation Phase (Phase IIa): HMPL-689:20 mg and 30 mg, QD orally in a therapeutic cycle of 28 days. Dose Expansion Phase (Phase IIb): HMPL-689 (RP2D) in a therapeutic cycle of 28 days

tazemetostat combined with HMP689 open-label treatment arm

Eligibility Criteria

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

You may qualify if:

• Willing and able to give informed consent, as documented by signed ICF
• Age ≥ 18 years
• Patients with histologically confirmed R/R lymphoma:
• Phase IIa （dose escalation study）: patients with relapsed or refractory lymphoma who have failed standard treatment and have no standard treatment options
• Phase IIb（ expansion Study ）: Cohort 1 (DLBCL, FL 3b) Histologically confirmed DLBCL, FL 3b (including primary mediastinal B-cell lymphoma) with relapsed/refractory disease
• Cohort 2 (FL) patients with histologically confirmed R/R FL (Grade 1, 2, 3a)
• Cohort 3 (MCL): Patients with R/R MCL who had prior therapies
• Cohort 4 (PTCL): Patients with histologically confirmed R/R PTCL who have failed or cannot tolerate standard therapy
• Patients must have at least one measurable lesion
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate bone marrow function, renal function and hepatic function:
• Currently human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) is inactive
• Female patients of childbearing potential must agree to use a double contraception method and male patients with partners of childbearing potential must also use an effective double contraception method during the study period and for 3 months after the final dose

You may not qualify if:

• Patients who have previously used EZH2 inhibitors and PI3K inhibitors, or previously could not tolerate EZH2 inhibitors or PI3K inhibitors
• Patients with brain metastases or leptomeningeal invasion
• Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 5.0 criteria) and any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS / AML/MPN)
• Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and multiple primary neoplasms (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, China

Location

MeSH Terms

Conditions

Lymphoma

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

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

Study Officials

• Bin Yang

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: February 6, 2023
• Study Start: February 13, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)