A Phase 1/2 Study of KHN922 for Injection to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity in Patients with Advanced Solid Tumors

This study can be divided into two parts: Phase I - dose escalation and dose backfill ; Phase II - cohort-expansion.This study is expected to last approximately 3 years from the time the first participant is enrolled to the time the last participant is off the study. The longest treatment period for a participant in this study will be 24 months. Participants who continue to derive clinical benefit from the study treatment in the absence of withdrawal of consent, Progressive disease (PD), or unacceptable toxicity may continue the study treatment until 24 months of treatment.

Phase I:The primary endpoints is to assess the safety and tolerability of KHN922 in patients with advanced solid tumors.The Safety and tolerability will be evaluated by monitoring and assessment of AEs, clinical laboratory tests (hematology, urinalysis, biochemistry, coagulation, etc.), physical examination findings, and vital signs measurements to determine Recommended Dose for Phase 2 clinical trials (RP2D).

Phase II:The primary endpoints is to assess the efficacy of KHN922.

Inclusion Criteria:1.Signed, written IRB-approved Informed Consent. 2.Male or female. 3.Aged 18 ~ 75 years. 4.Life expectancy of at least 3 months. 5.Histologically or cytologically confirmed advanced or unresectable solid tumors for wihch failure or difficult to be treated with standard therapies, or not suitable for standard therapies.

6.Measurable disease by CT/MRI as defined in RECIST v1.1. 7.Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

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Exclusion Criteria:

1.Pregnant or lactating women. 2.Received cancer-directed therapy within the following timeframes:

• Major surgery within 4 weeks or will be expected to require major surgical treatment during the study period.

• Radical radiotherapy or chest palliative radiotherapy within 4 weeks, or palliative radiotherapy at any other sites except chest within 2 weeks.

• Antibody-based anti-cancer therapies, macromolecular protein products or cytotherapies within 4 weeks.

• Hormonal anti-tumor therapy within 2 weeks.

• Chemotherapy (including non-antibody based immunotherapy therapy) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or 5 times half life of the chemotherapeutic agent (whichever is longer).

• Any natural medicine with anti-tumor effect within 1 weeks.

• Tyrosine kinase inhibitor (TKI) treatment within 1 week. 3.Received experimental drug therapy or participated in a clinical study of a medical device within 4 weeks prior to first infusion of KHN922.

  4.Known history of unstable angina, myocardial infarction (MI), or congestive heart failure (CHF) (NYHA Class II-IV) within 6 months or clinically significant arrhythmia (other than stable atrial fibrillation or paroxysmal superventricular tachycardia) requiring anti-arrhythmia therapy 5.Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) and/or diabetes (HbA1c ≥ 8.0%).

  6.serous cavity effusion such as ascites or pleural effusion requiring drainage within 14 days before the first dose of medication. 7.Patients with moderate to severe respiratory dyspnea due to severe primary lung disease or complications of advanced malignancy [rated as grade 3/4 by modified Medical Research Council (mMRC) scale] (see Appendix 3), or requiring continuous oxygen therapy, or acute exacerbations of chronic obstructive pulmonary disease (AECOPD), or current abnormal and clinically significant of interstitial lung disease (ILD)/pneumonia, or ILD/ pneumonia that could not be ruled out on imaging during screening, or any autoimmune disease/connective tissue disease (e.g. Rheumatoid arthritis, Sjogren's syndrome, sarcoidosis) with lungs involvement.

  8.Grade ≥2 anorexia, nausea, vomiting, or diarrhea within 2 weeks prior to first infusion of KHN922.

  9.Active central nervous system (CNS) metastasis (defined as untreated and has symptoms such as consciousness disorder, or need steroid or anticonvulsant therapy to control symptoms) within 1 month prior to first infusion of KHN922.

  10.History of significant active bleeding, intestinal obstruction, gastrointestinal perforation, or other severe gastrointestinal diseases within 6 months prior to first infusion of KHN922.

  11.Newly diagnosed thromboembolic events requiring treatment within 6 months prior to first infusion of KHN922.

  12.Known history of other malignancies diagnosed within 5 years prior to first infusion of KHN922 (patients with basal cell carcinoma, skin squamous cell carcinoma and carcinoma in situ, and with radical resection for more than 3 years could be enrolled).

  13.Known to be allergic to any component of KHN922, or known history of grade ≥3 anaphylaxis to macromolecular protein products/antibody-based therapy, or known history of grade ≥3 drug-related AEs with the use of topoisomerase I inhibitors such as irinotecan.

  14.Patients who require use of strong inhibitors or inducers of CYP3A4 at least 14 days prior to the first infusion of KHN922 and throughout study. Use of strong inhibitors or inducers of CYP3A4 is not allowed in this study.

  15.Positive for Human Immunodeficiency Virus (HIV) antibody; active Hepatitis B Virus (HBV) [subjects with positive HBsAg or HBcAb in this study need to be tested for HBV DNA, and if HBV DNA > 500 IU/mL (or 2500 copies/ml), they will be excluded. For subjects with positive HBsAg or HBcAb, it is allowed to receive antiviral treatment until HBV-DNA reaches ≤ 500 IU/ml (or 2500 copies/ml) before enrollment in the study]; positive for HCV antibody and HCV-RNA above the lower limit of measurability or 1000 copies/mL (whichever is lower); subjects with untreated or currently treated tuberculosis as diagnosed through inquiry.

  16.Known history of allogeneic cell or solid organ transplantation. 17.Active infection requiring systemic treatment within 2 weeks prior to the first infusion of KHN922.

  18.Confirmed Gilbert's syndrome 19.Live or live attenuated vaccine within 28 days prior to KHN922 administration and live or live attenuated vaccine planned over the course of the study.

  20.Known history of psychotropic substance abuse, alcohol abuse, or drug abuse. 21.Psychological, social, familial, or geographical factors that would prevent regular follow-up. Adults under guardianship, curatorship, safeguard of justice, or family empowerment measure are not eligible.

  22.Otherwise considered inappropriate for the study by the investigator.