A Study to Evaluate YH001 in Combination With Toripalimab in Subjects With Advanced NSCLC and HCC

Inclusion Criteria

• •1. Male or female, aged ≥ 18 years；
• •2. Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
• •3. Target Population
• •Cohort A:
• •* Have histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous)
• •* Recurrent or unresectable locally advanced (Stage IIIB) or metastatic (Stage IV);
• •* Naïve to any systemic anti-cancer therapy
• •* No EGFR mutation or ALK/ ROS1 gene rearrangement
• •* PD-L1 positive (TPS≥1%) NSCLC
• •Cohort B:
• •* HCC diagnosis confirmed by or radiology, histology, or cytology;
• •* Barcelona Clinic Liver Cancer (BCLC) Stage C or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy and not amenable to a curative treatment approach;
• •* Child-Pugh A liver score within 7 days prior to first dose of study drug;
• •* Documented objective radiographic progression during or after treatment with sorafenib/lenvatinib, or intolerant of sorafenib/lenvatinib; or documented objective radiographic progression during or after treatment with atezolizumab and bevacizumab, or intolerant of atezolizumab and bevacizumab.
• •4. At least 1 unidimensional measurable target lesion per RECIST v1.1
• •5. ECOG performance status score 0 or 1
• •6. Have life expectancy of at least 12 weeks based on investigator's judgement.
• •7. Adequate organ and bone marrow function:
• •8. Women of reproductive potential must have negative serum beta human chorionic gonadotropin (β -HCG) pregnancy test within 7 days of the fist dose of YH001.
• •9. Women of reproductive potential who are sexually active with a non-sterilized male must consistently use highly effective contraception/birth control between signing of the informed consent and 120 days after the last administration of the study drug.
• •14. Clinically uncontrolled concurrent illnesses, including, but not limited to, active infection that requires systematic treatment, serious diabetes (fasting blood glucose \> 250 mg/dl), psychiatric illness that would limit compliance with the study requirements and other serious medical illnesses requiring systemic therapies.
• •15. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ Grade 1 per CTCAE v5.0
• •16. Failure to recover adequately, as judged by the investigator, from prior surgical procedures; the subjects have had major surgery within 28 days, or minor surgery within 2 weeks prior to the first dose of YH001.
• •17. Subjects received any live or attenuated vaccine within 28 days prior to the first dosing of study drug. For inactivated or attenuated COVID -19 vaccine, follow local guidelines.
• •18. Pregnant or breast-feeding females.
• •19. Any clinically significant abnormality in the laboratory
• •20. Subjects have another active invasive malignancy within 5 years
• •21. Cohort B:
• •* History of esophageal or gastric variceal bleeding within the last 6 months, or current active gastrointestinal bleeding;
• •* Large tumor lesion in liver (≥60% liver volum), portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging;
• •* Clinically diagnosed hepatic encephalopathy in the last 6 months