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

NCT ID: NCT05713110

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-13
• Study Completion Date: 2024-12-31

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).

Detailed Description

Dose Escalation Phase (Phase IIa ):Including 10-20 patients for dose escalation, the enrollment will continue until about 10 patients in the dose group with response, as to determine Recommended Phase II dose (RP2D).

Dose Expansion Phase (Phase IIb):Multiple expansion cohorts will be set up according to different tumor types, and about 15-20 patients will be enrolled in each cohort to further observe the anti-tumor effect of Tazemetostat combined with HMPL-689 in different pathological types of R/R lymphoma.

This study is expected to enroll 85-140 patients total in Phase IIa and phase IIb.

Conditions

Relapsed/Refractory Lymphoma

Study Design

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

Study Groups

tazemetostat combined with HMP689 open-label treatment arm

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

Group Type: EXPERIMENTAL

tazemetostat

Intervention Type: 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

HMPL-689

Intervention Type: 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

Interventions

tazemetostat

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

Intervention Type: DRUG

HMPL-689

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Willing and able to give informed consent, as documented by signed ICF

2. Age ≥ 18 years

3. 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

4. Patients must have at least one measurable lesion

5. Life expectancy ≥ 12 weeks

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

7. Adequate bone marrow function, renal function and hepatic function:

8. Currently human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) is inactive

9. 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

Exclusion Criteria

1. Patients who have previously used EZH2 inhibitors and PI3K inhibitors, or previously could not tolerate EZH2 inhibitors or PI3K inhibitors

2. Patients with brain metastases or leptomeningeal invasion

3. 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)

4. 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

• 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

Bin Yang

Role: STUDY_DIRECTOR

Hutchison Medipharma Limited

Locations

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Countries

China

Other Identifiers

2021-TAZ-00CH2

Identifier Type: -

Identifier Source: org_study_id