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Recruiting Phase 1/2

Evaluate the Safety and Clinical Activity of HH2853

NCT04390737 · tracked via the Priya Life Science China tracker
Phase
Phase 1/2
Started
2020-09-08
Last updated
2026-01-30

Condition(s) studied

FL LymphomaEpithelioid SarcomaPeripheral T Cell LymphomaAdvanced Solid Tumor

Investigational drug(s) / intervention(s)

HH2853 Tablets →

HH2853 Tablets: 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.

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion criteria: 1. Provided signed written informed consent prior to initiation of any study-related procedures; 2. Males and females ≥ 18years of age at the time of consent are obtained (or meet the country's regulatory defined adult legal age); 3. 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: 1. Histologically or cytologically documented advanced recurrent or metastatic solid tumor. 2. 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.) 3. 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. For epithelioid sarcoma in Phase I and Phase II cohort 2: 1. Confirmed by local histology or cytology 2. Patients with unresectable locally delayed or metastatic epithelioid sarcoma who have undergone treatment (including those who have failed treatment and developed intolerable toxicity). For solid tumors in Phase I and Phase II queue 3: 1. Confirmed by local pathology as advanced recurrent or metastatic solid tumor. 2. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1; 5. Availability of archival tissue within three years 6. Relapsed/Refractory FL, Epithelioid sarcoma, relapsed/refractory PTCL, other relapsed/refractory non-Hodgkin's lymphomas with EZH2 mutation, and advanced solid tumors with specific genetic alterations, including EZH2 mutation, INI1 deficiency, BAP1 deficiency, ARID1A mutation, or/and SMARCA4 mutation 7. Predicted life expectancy of ≥ 3 months; 8. Patient must meet the following laboratory values: 1.Serum total Bilirubin ≤ 1.5 x ULN or ≤ 3.0 mg/dL for patients with Gilbert's syndrome 2.AST/SGOT and ALT/SGPT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present 3.24-hour creatinine clearance (calculated\* or measured value\*\*)≥ 50 mL/min 4.Platelets ≥ 1 x LLN (no Platelet transfusion for 7 days prior to screening) 5.Hemoglobin (Hgb) ≥ 9 g/dL 6.Absolute Neutrophil Count (ANC) ≥ 1.0 x 10\^9/L 7.Adequate coagulation function: International normalized ratio (INR) \<1.3 (or \<3.0 on anticoagulants) 9. Measurable lesion Exclusion Criteria: 1. 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. 2. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease. 3. Patients with prior transplant are excluded; 4. Major surgery within 4 weeks prior to first dose; 5. A prohibited medication or expected to require any of these medications during treatment with study drug within 2 weeks of first dose; 6. 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). 7. Concomitant malignancies or previous malignancies 8. 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. 9. Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1 10. There were ≥ 3 lesions with punctate bleeding, any active bleeding, intratumoral bleeding, known bleeding tendencies, or treatment with antiplatelet/antithrombotic drugs. 11. Gastrointestinal condition which could impair absorption of study medication; 12. Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol; 13. Cardiac exclusion criteria: 1.History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 3 months prior to first dose of study drug; 2.Fridericia's corrected QT interval (QTcF) \> 450 ms (for male) and \> 470 ms (for female) on ECG conducted during screening; 3.Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or family history of unexplained sudden death; 4.History or current evidence of serious uncontrolled ventricular arrhythmias; 5.Symptomatic congestive heart failure (Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system) within the previous 3 months; 6.Left ventricular ejection fraction (LVEF) \< 50%; 14. Any evidence of serious active infections requiring antibiotics; 15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or their excipients; 16. Pregnant or breast-feeding female; 17. Contraception: 18. Other serious illness or medical conditions at the Investigator's discretion, that may influence study results 19. Previously received treatment with EZH2 or EZH1/2 inhibitors. 20. Grade 3b FL or evidence of transformation to invasive lymphoma

Primary outcome measure(s)

  • Maximum tolerated Dose (MTD) — 28-day treatment cycles
    Determine MTD of HH2853
  • Recommended phase II dose (RP2D) — 28-day treatment cycles
    Determine RP2D of HH2853
  • Adverse events assessed according to NCI-CTCAE V5.0 — 28-day treatment cycles
    Evaluate the safety of HH2853
  • Dose limiting toxicities (DLT) — 28-day treatment cycles
    Evaluate the tolerability of HH2853
  • Objective response rate (ORR) — 28-day treatment cycles
    Assess the preliminary efficacy of HH2853

Trial sites (25)

FacilityCityRegionStatus
Mayo Clinic Phoenix Arizona Completed
Mayo Clinic Jacksonville Florida Completed
Mayo Clinic Rochester Minnesota Completed
NEXT Oncology San Antonio Texas Completed
The First Affiliated Hospital of Anhui Medical University Hefei Anhui Recruiting
Beijing Cancer Hospital Beijing Beijing Municipality Recruiting
Beijing Cancer Hospital Beijing Beijing Municipality Recruiting
Beijing Jishuitan Hospital Beijing Beijing Municipality Recruiting
Sun Yat-Sen University Cancer Hospital Guangzhou Guangdong Recruiting
Affiliated Tumor Hospital of Guangxi Medical University Nanning Guangxi Recruiting
Henan Cancer Hospital Zhengzhou Henan Recruiting
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan Hubei Recruiting
Hunan Cancer Hospital Changsha Hunan Recruiting
Affiliated Drum Tower Hospital, Medical School of Nanjing University Nanjing Jiangsu Recruiting
Liaoning Cancer Hospital&Institute Shenyang Liaoning Recruiting
Shengjing Hospital Of China Medical University Shenyang Liaoning Recruiting
Linyi Tumor Hospital Linyi Shandong Recruiting
Shanghai Sixth People's Hospital Shanghai Shanghai Municipality Recruiting
Zhongshan Hospital Fudan University Shanghai Shanghai Municipality Recruiting
Shanxi Cancer Hospital Taiyuan Shanxi Recruiting
West China Hospital of Sichuan University Chengdu Sichuan Recruiting
Tianjin Cancer Hospital Tianjin Tianjin Municipality Recruiting
Zhejiang Cancer Hospital Hangzhou Zhejiang Recruiting
Beijing Cancer Hospital Beijing China Recruiting
Sun Yat-Sen University Cancer Hospital Guangzhou China Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04390737 on ClinicalTrials.gov ↗ ← All trials in China