A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of HH2853 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphomas or Advanced Solid Tumors

Haihe Biopharma Co., Ltd.23 sites in 2 countries254 target enrollmentSeptember 8, 2020

ConditionsFL Lymphoma Epithelioid Sarcoma Peripheral T Cell Lymphoma Advanced Solid Tumor

InterventionsHH2853 Tablets

DrugsHH2853 Tablets

Overview

Phase: Phase 1
Intervention: HH2853 Tablets
Conditions: FL Lymphoma
Sponsor: Haihe Biopharma Co., Ltd.
Enrollment: 254
Locations: 23
Primary Endpoint: Recommended phase II dose (RP2D)
Status: Recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Detailed Description

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)

Registry

clinicaltrials.gov

Start Date

September 8, 2020

End Date

December 31, 2028

Last Updated

3 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Haihe Biopharma Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provided signed written informed consent prior to initiation of any study-related procedures;
•Males and females ≥ 18years of age at the time of consent are obtained (or meet the country's regulatory defined adult legal age);
•Tumor type criteria:
•The specific requirements for specific subtypes of recurrent/refractory non Hodgkin's lymphoma (NHL) confirmed by histology are as follows:
•Histologically confirmed follicular lymphoma (FL) that has been treated with at least two lines of systemic therapy (at least one regimen based on anti-CD20 monoclonal antibodies) according to GELF criteria or as determined by researchers (Grade 1-3a); Relapsed/refractory diffuse large B-cell lymphoma - non-specific (DLBCL NOS, 2016 World Health Organization Lymphoma Classification) that has received at least two treatment regimens in the past (at least one with CD20 monoclonal antibody as the main treatment, with a maximum number of treatment lines\<5), and is not a candidate for salvage treatment or autologous/allogeneic stem cell transplantation.
•Relapsed/refractory clinicopathologically documented PTCL with at least 1 line of prior systemic treatment (maximum \<5 lines). Solid tumors that meet the following criteria:
•Histologically or cytologically documented advanced recurrent or metastatic solid tumor.
•Phase I dose escalation: Measurable or evaluable lesions by RECIST v1.1 in at least 1 site; phase I dose extension and phase II: Measurable target lesions by RECIST v1.1 in at least 1 site. (Lesions that have been treated with radiotherapy or other local treatment are generally considered unmeasurable unless there is definite progression of the lesion.)
•Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. One of the following criteria should be met.
•Patients must experience at least one prior standard therapy. Disease progression occurred on or after last line of therapy, or intolerant to last line of therapy (maximum ≤3 lines, Patients without treatment options available known to provide clinical benefit are also eligible upon agreement from investigator and sponsor) There is no approved therapy, or for which standard therapy is unsuitable or refused by patients after being fully informed.

Exclusion Criteria

•Any cancer-directed therapy within 28 days or five half-lives prior to first dose; Small molecule anticancer therapy within 2 weeks or five half-lives; Local radiotherapy within 14 days of first dose.
•Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
•Patients with prior transplant are excluded;
•Major surgery within 4 weeks prior to first dose;
•A prohibited medication or expected to require any of these medications during treatment with study drug within 2 weeks of first dose;
•HIV (human immunodeficiency virus) infection, active hepatitis B or hepatitis C patients (HBsAg positive patients with HBV (hepatitis B virus) DNA ≥ 10\^3 copies or ≥ 200 IU/mL; HCV antibody test results are positive, and HCV (hepatitis C virus) RNA PCR test results are positive).
•Concomitant malignancies or previous malignancies
•Concurrent use of therapeutic warfarin is allowed. However, anticoagulants that do not have reversal agents available are prohibited except low molecular weight heparin and direct oral anticoagulants.
•Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1
•There were ≥ 3 lesions with punctate bleeding, any active bleeding, intratumoral bleeding, known bleeding tendencies, or treatment with antiplatelet/antithrombotic drugs.

Arms & Interventions

HH2853 administered on a BID schedule in continuous 28-day treatment cycles

HH2853 is supplied as tables with dosage strength of 25mg and 200mg. HH2853 Tablet will be administered orally on a continuous twice daily (BID) schedule, on a flat scale of mg and not individually adjusted by weight or body surface area. A treatment cycle is defined as 28 days for the purposes of scheduling procedures and evaluations. All patients will be treated with HH2853 orally on a continuous BID schedule, beginning on Cycle 1 Day 1. But patients in accelerated titration (ATD) part should be administered a single dose on the first day in order to evaluate the PK of a single dose administration. Dosing is twice daily from the second day thereafter.

Intervention: HH2853 Tablets