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
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.
• 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.
⁃ For epithelioid sarcoma in Phase I and Phase II cohort 2:
• Confirmed by local histology or cytology
• 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:
• Confirmed by local pathology as advanced recurrent or metastatic solid tumor.
• 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