This is an open-label, multicenter, first-in-human phase I/II study which is composed of 3 parts: phase I dose escalation, phase I dose extension and phase II. HH2853 will be administered orally on a continuous BID schedule on a continuous 28-day treatment cycle.
Phase I: Phase I dose escalation The accelerated titration (ATD) incorporated with Bayesian Optimal Interval design (BOIN) will be used to assess the DLT, safety, tolerability, MTD and furthermore, to establish the RP2D. DLT assessment is only applicable to phase I dose escalation. Eligible patients will be enrolled in the ascending dose until MTD/RP2D is established. Phase I dose extension During the dose escalation phase, a dose extension with additional patients will be included in order to further evaluate the tolerability, pharmacokinetics, and efficacy at doses that have been evaluated as safe. The number of patients to be enrolled in each dose extension cohort is up to 15, but the final number of dose level can be determined and the final patient number at each dose level can be adjusted slightly based on available safety, efficacy, PK, and PD data upon agreement from sponsor and investigators (e.g. safety evaluation meeting). For phase I dose extension, approximately 30 patients will be enrolled based on initial estimate, but the final total number of patients will depend on the number of dose levels extended and patient number at each dose level. The total number of patients is estimated to be approximately 60 patients for phase I dose escalation and dose extension, but the final total number of patients will depend upon the number of dose cohorts to reach MTD/RP2D, and patient number at each dose level. Phase II(China Only): Phase II is planned after the completion of phase I. Up to approximately 193 patients will be enrolled as outlined below: * Cohort 1: Relapsed/Refractory FL (n≈56) * Cohort 2: Epithelioid sarcoma (n≈77) * Cohort 3: Relapsed/Refractory PTCL, other relapsed/refractory Non-Hodgkin's lymphomas with EZH2 mutation, or advanced solid tumors with specific genetic alterations, including EZH2 mutation, INI1 deficiency, BAP1 deficiency, ARID1A mutation, or/and SMARCA4 mutation (n≈60)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
254
Proposed daily dose (BID): 50mg, 100mg, 200mg, 400mg, 600mg, 800mg, 1000mg. It is possible for additional and/or intermediate dose levels to be added during the course of the study. Cohorts may be added at any dose level below the MTD in order to better understand safety, PK or PD.
Mayo Clinic
Maximum tolerated Dose (MTD)
Determine MTD of HH2853
Time frame: 28-day treatment cycles
Recommended phase II dose (RP2D)
Determine RP2D of HH2853
Time frame: 28-day treatment cycles
Adverse events assessed according to NCI-CTCAE V5.0
Evaluate the safety of HH2853
Time frame: 28-day treatment cycles
Dose limiting toxicities (DLT)
Evaluate the tolerability of HH2853
Time frame: 28-day treatment cycles
Objective response rate (ORR)
Assess the preliminary efficacy of HH2853
Time frame: 28-day treatment cycles
AUClast
Characterize the pharmacokinetic profile of HH2853
Time frame: 28-day treatment cycles
AUCinf
Characterize the pharmacokinetic profile of HH2853
Time frame: 28-day treatment cycles
Cmax
Characterize the pharmacokinetic profile of HH2853
Time frame: 28-day treatment cycles
Tmax
Characterize the pharmacokinetic profile of HH2853
Time frame: 28-day treatment cycles
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Phoenix, Arizona, United States
Mayo Clinic
Jacksonville, Florida, United States
COMPLETEDMayo Clinic
Rochester, Minnesota, United States
COMPLETEDNEXT Oncology
San Antonio, Texas, United States
COMPLETEDThe First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGBeijing Jishuitan Hospital
Beijing, Beijing Municipality, China
RECRUITINGSun Yat-Sen University Cancer Hospital
Guangzhou, Guangdong, China
RECRUITINGAffiliated Tumor Hospital of Guangxi Medical University
Nanning, Guangxi, China
RECRUITING...and 15 more locations
CL/F
Characterize the pharmacokinetic profile of HH2853
Time frame: 28-day treatment cycles
Vz/F
Characterize the pharmacokinetic profile of HH2853
Time frame: 28-day treatment cycles
Terminal half-life (T1/2)
Characterize the pharmacokinetic profile of HH2853
Time frame: 28-day treatment cycles
Duration of response (DoR)
Assess the preliminary efficacy of HH2853
Time frame: 28-day treatment cycles
Progression-free survival (PFS)
Assess the preliminary efficacy of HH2853
Time frame: 28-day treatment cycles
Disease control rate (DCR)
Assess the preliminary efficacy of HH2853
Time frame: 28-day treatment cycles
Time to response (TTR)
Assess the preliminary efficacy of HH2853
Time frame: 28-day treatment cycles
Time to progression (TTP)
Assess the preliminary efficacy of HH2853
Time frame: 28-day treatment cycles
Clinical Outcome
Explore the association between potential biomarker and the clinical outcome
Time frame: 28-day treatment cycles