Evaluate the Safety and Clinical Activity of HH2853

• Status: Recruiting
• Trial end date: 2023-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, multicenter, first-in-human phase I dose escalation study. HH2853 will be administered orally on a continuous BID schedule on a continuous 28-day treatment cycle. 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Haihe Biopharma Co., Ltd.; ShangHai HaiHe Pharmaceutical

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:

1. Relapsed/refractory histologically documented non-Hodgkin's lymphoma (NHL) must have received at least 2 prior systemic therapies and should meet the following criteria:

• Follicular lymphoma (FL) must meet criteria requiring systemic treatment per the GELF criteria and there is no standard salvage regimen available;

• Diffuse large B-cell lymphoma NOS (2016 WHO classification of lymphoma neoplasms) relapsed or refractory with at least 2 prior regimen (e.g., rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone [R-CHOP]) and not a candidate for standard salvage regimens or autologous or allogeneic stem cell transplant.

Patients without treatment options available known to provide clinical benefit are also eligible.

2. Solid tumors that meet the following criteria: histologically or cytologically documented advanced recurrent or metastatic solid tumor. Measurable or evaluable disease by RECIST v1.1 in at least 1 site; disease progression with the last line of therapy and at least one prior standard of care regimens, or tumor for which there is no approved therapy, or for which standard therapy is unsuitable or refused. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. Patients without treatment options available known to provide clinical benefit are also eligible.

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1;

5. Predicted life expectancy of ≥ 3 months;

6. 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

*For calculated creatinine clearance (Ccr) value, the eligibility should be determined using the Cockcroft-Gault formula:

1. Male Ccr (mL/mim) = body weight (kg) x (140-age)/[72 x creatinine (mg/dL)]

2. Female Ccr (mL/min) = male Ccr x 0.85 ** A measured value Ccr value (i.e. not calculated) should meet this criterion.

4. Platelets ≥ 100 x 10^9/L (no Platelet transfusion for 7 days prior to screening)

5. Hemoglobin (Hgb) ≥ 9 g/dL (no RBC transfusion for 7 days prior to screening)

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)

Exclusion Criteria:

1. Any cancer-directed therapy (chemotherapy, antibody therapy, radiotherapy, hormonal therapy, biologic or immunotherapy, Chinese medicine/Chinese patent medicine with anti-tumor effect, etc.) within 28 days;

2. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease. Note: Any major surgery, radiotherapy or immunotherapy within the 4 weeks prior to first dose of study drug, or palliative radiotherapy to a single symptomatic lesion within the 2 weeks prior to first dose of study drugs;

3. Patients with prior transplant are excluded; however, patients who have previously received an autologous stem cell transplant are allowed if a minimum of 100 days has elapsed from the time of transplant and the patient has recovered from transplant-associated toxicities prior to the first dose of HH2853. Patients who have previously received an allogeneic stem cell transplant are also allowed if a minimum of 6 months has elapsed prior to the first dose of HH2853;

4. Major surgery within 4 weeks prior to first dose;

5. Current use of a prohibited medication or expected to require any of these medications during treatment with study drug (see Section 6.4);

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). However, patients that can be controlled with treatment are eligible;

7. Concomitant malignancies or previous malignancies with less than 2 years of disease-free interval at the time of enrollment (but basal cell carcinoma skin cancer, cervical CIS (carcinoma in situ), CIS of the breast, localized or low Gleason grade prostate cancer, and < T2 bladder cancer can be included);

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 (see Section 6.4).

9. Any toxicities from prior treatment that have not recovered to ≤ CTCAE Grade 1 before the start of study drug, with exception of hair loss or fatigue;

a) Lymphoma patients with ≤ Grade 3 lymphopenia can be enrolled at the discretion of the investigator

10. Packed red blood cell or platelet transfusion within 7 days of screening laboratory tests;

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. QTc F interval >470 msec

3. History or current evidence of serious uncontrolled ventricular arrhythmias

4. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system, see Appendix 14.5) within the previous 3 months; if > 3 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms.

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 (See Appendix 14.4):

Patients who do not meet the following requirements will be excluded:

• For women: negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal (defined as no menstrual cycle for at least 12 consecutive months), or compliant with an acceptable contraceptive regimen (2 highly effective forms, such as oral contraceptives, condom with spermicide, etc.) during and for 3 months after the treatment period. Abstinence is not considered as an adequate contraceptive regimen;

• For men: must be surgically sterile, or compliant with a contraceptive regimen (as above) during and for a minimum of 3 months after the treatment period.