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

A Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Tazemetostat in Combination With HMPL-689 in Patients With Relapsed/Refractory Lymphoma

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).

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.

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