Evaluate the Safety and Clinical Activity of HH2853

Launched by HAIHE BIOPHARMA CO., LTD. · May 14, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called HH2853 to see how safe it is and how well it works for patients with certain types of cancers, including follicular lymphoma, epithelioid sarcoma, peripheral T cell lymphoma, and advanced solid tumors. The trial is open to adults aged 18 and older who have already tried at least two treatment options for their cancer and have not seen improvements. Participants must be able to understand the study and provide signed consent before joining.

If eligible, participants will take HH2853 by mouth twice a day for 28 days at a time. The trial is currently recruiting new patients and is designed to monitor their health closely throughout the study. It's important to note that there are specific health criteria that must be met, and certain conditions or previous treatments may exclude someone from participating. This trial offers a chance to access a new treatment option while contributing to research that could benefit others in the future.

Gender

ALL

Eligibility criteria

• 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