Overview
This is a Phase I Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of IAP0971 in Patients with Advanced Malignant Tumors.
Description
The study includes three phases: dose escalation (Phase Ia), dose extension (Phase Ib), and clinical exploration (Phase IIa).First, the Phase Ia dose escalation will be carried out. After finishing the Phase 1a，the Phase Ib dose extension study can be carried out in the MTD dose which can be achieved from Phase 1a. After Phase Ia & Ib are completed and RP2D is obtained, Phase IIa clinical exploratory research can be carried out.
Eligibility
Inclusion Criteria:
- 1. Age 18 to 80 years, male or female. 2. Patients with histologically or cytologically confirmed advanced or unresectable solid tumors or and relapsed and/or refractory non-Hodgkin's lymphoma, who have progressed on or have been intolerant to standard treatment, or for whom no standard treatment exists. 3. Dose Escalation Phase (Part A)：At least one evaluable tumor lesion per RECIST 1.1 (solid tumors) or Lugano 2014 (lymphomas).
Dose Expansion Phase (Part B)：At least one measurable tumor lesion per RECIST 1.1 (solid
tumors) or Lugano 2014 (lymphomas).
4. Agree to provide previously stored tumor tissue specimens or perform biopsy to collect
tumor lesion tissue and send it to the central laboratory for PD-L1 expression level
detection.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. (see Appendix 3)
6. Adequate organ function: Hematological system (No blood transfusion or hematopoietic
stimulating factor therapy within 14 days) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
White blood cell count (WBC) ≥ 3.0 × 109/L Platelets (PLT) ≥ 75 × 109/L Hemoglobin (Hb) ≥
90 g/L Hepatic function Total bilirubin (TBIL) ≤ 3 × ULN Alanine aminotransferase (ALT) ≤ 3
× ULN; Aspartate aminotransferase (AST) ≤ 3 × ULN; Renal function Creatinine clearance
(Ccr) (only calculated if creatinine > 3 × ULN) ≥ 50 mL/min (calculated according to
Cockcroft-Gault formula, see Appendix 7 for formula) Coagulation function Activated partial
thromboplastin time (APTT) ≤ 1.5 × ULN International normalized ratio (INR) ≤ 1.5 × ULN 7.
Expected survival time of more than 3 months. 8. Eligible patients of childbearing
potential (men and women) must agree to use a reliable method of contraception (hormonal or
barrier method or abstinence, etc.) with their partners during the trial and for at least
90 days after study drug administration; female patients of childbearing potential (see
Appendix 8 for definition) must have a negative blood or urine pregnancy test 7 days before
the first administration.
9. Subjects must be informed of the study prior to the trial and voluntarily sign a written
informed consent form.
Exclusion Criteria:
- 1. Patients who have a severe hypersensitivity reaction to any monoclonal antibody (CTCAE
5.0 grade ≥ 3).
2. Patients who received chemotherapy, radiotherapy, biological therapy, endocrine therapy,
immunotherapy, and other anti-tumor treatment within 4 weeks before the first
administration, except for the following: Nitrosourea or mitomycin C was received within 6
weeks before the first administration; Oral fluoropyrimidines and small molecule targeted
drugs within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to the first
administration.
Chinese proprietary medicines with anti-tumor indications were received within 2 weeks
before the first administration.
3. Receipt of other non-marketed investigational drugs or treatments within 4 weeks before
the first administration.
4. Patients who have undergone major organ surgery (excluding needle biopsy) or have
significant trauma within 4 weeks before the first administration, or require elective
surgery during the trial.
5. Patients who have received systemic glucocorticoids (prednisone > 10 mg/day or
equivalent doses of similar drugs) or other immunosuppressive agents within 14 days before
the first administration; exclude the following conditions: topical, ophthalmic,
intra-articular, intranasal or inhaled corticosteroid therapy; short-term use of
glucocorticoid for preventive treatment (for example, prevention of contrast agent
allergy).
6. Patients who have received immunomodulatory drugs within 14 days before the first
administration, including but not limited to thymosin, interleukin-2, interferon, etc.
7. Patients who have received live attenuated vaccines within 4 weeks before the first
administration.
8. Previous allogeneic hematopoietic stem cell transplantation or organ transplantation.
9. The adverse reactions caused by previous anti-tumor treatment have not recovered to
CTCAE 5.0 grade ≤ 1 (except for toxicity without safety risk as judged by the investigator,
such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone
replacement therapy, etc.).
10. Patients with active infection who need intravenous anti-infective therapy. 11.
Patients with interstitial lung disease (except for radiation pulmonary fibrosis not
requiring hormone therapy).
12. History of serious cardiovascular and cerebrovascular diseases, including but not
limited to: Patients with severe cardiac rhythm or conduction abnormalities, such as
arrhythmia requiring clinical intervention, second-degree to third-degree atrioventricular
block; QT interval (QTcF) corrected by Fridericia's method > 470 ms (see Appendix 9 for
calculation formula); Acute coronary syndrome, congestive heart failure, aortic dissection,
stroke or other grade 3 and above cardiovascular and cerebrovascular events within 6 months
prior to the first dose; Patients with heart failure with cardiac function class ≥ II
according to New York Heart Association (NYHA) (see Appendix 4) or Left Ventricular
Ejection Fraction (LVEF) < 50%; Clinically uncontrolled hypertension. 13. Patients who
currently have active or have had autoimmune diseases that may have recurrence (such as
systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for
clinically stable autoimmune thyroid diseases, type I Diabetics.
14. Patients who have received immunotherapy and developed irAE ≥3 or immune-related
myocarditis ≥2.
15. Clinically uncontrolled effusion in the third space, which is not suitable for
enrollment based on the investigator's judgment.
16. Known alcohol or drug dependence. 17. Patients with mental disorders or poor
compliance. 18. Women who are pregnant or breastfeeding. 19. The subject has a history of
other serious systemic diseases or other reasons that make the subject unsuitable for this
clinical study in the opinion of the investigator.