Phase Ib/II Trial of Envafolimab Plus Lenvatinib for Subjects With Solid Tumors

Envafolimab(KN035) in Combination With Lenvatinib in the Treatment of Advanced Solid Tumors: a Multicenter, Open-label, Phase Ib/II Study

This is an open-label, multi-center study of Phase Ib/II study to assess the efficacy and safety of Envafolimab combinded with Lenvatinib in the treatment of subjects with advanced solid tumors. The primary hypothesis of this study is that subjects will have a better objective response rate (ORR) when treated with Envafolimab plus Lenvatinib than SOC.

Inclusion Criteria:

1. Eighteen years and older;
2. phase Ib:Histological or cytological diagnosis of Locally advanced or metastatic solid tumors (excluding hepatocellular carcinoma and thyroid carcinoma) that have progressed after standard treatment or are intolerant or have no effective treatment;
3. phase II cohort 1:Histological or cytological diagnosis of NSCLC，RCC, HCC, resistance to previous treatment with PD-(L)1 inhibitor; previous system treatment lines≤2;
4. phase II cohort 2：Unresectable locally advanced or metastatic or recurrent RCC;
5. Tumor tissue samples or biopsies from FFPE archived or fresh biopsies with locally advanced/metastatic disease must be provided, and if biopsies are not available, samples obtained prior to receiving adjuvant/neoadjuvant chemotherapy are allowed;
6. phase Ib and phase II cohort 1: Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or 1; Phase II cohort 2: Karnofsky physical status (KPS) assessment ≥70；
7. Life expectancy of at least 12 weeks;
8. At least one measurable lesion per RECIST 1.1;
9. Adequate organ function;
10. Signed informed consent.

Exclusion Criteria:

1. Prior anticancer treatment within 4 weeks prior to the first dose of study drugs;
2. Toxicity from prior anticancer therapy prior to the first dose of study drugs not recovered to ≤ grade1;
3. Hypertension did not satisfactory controlled after antihypertensive medication
4. Phase Ib/II: Subjects who were previously treated with Lenvatinib or who participated in a clinical trial of a generic version of Lenvatinib
5. Phase II cohort 1, intolerance to treatment with A PD-(L)1 inhibitor; History of severe digestive disease that can affect the oral absorption of Lenvatinib/Sunitinib;
6. Uncontrollable or significant cardiovascular or cerebrovascular disease;
7. Active, known history or suspected autoimmune disease;
8. Have used or require treatment with >10 mg/day of prednisone or an equivalent dose of systemic corticosteroids within 14 days prior to the first dose of study drugs;
9. have received live attenuated vaccine within 28 days prior to the first study drug treatment or are scheduled to receive it during the study period;
10. Subjects with known or suspected interstitial pneumonia;
11. Any serious active infection requiring systemic antibacterial, antifungal or antiviral therapy at screening, including active tuberculosis; Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
12. Active hepatitis B or hepatitis C;
13. Known history of severe gastrointestinal bleeding or active hemoptysis or other severe bleeding within 6 months prior to first study drug therapy;
14. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage ;
15. Known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis;
16. Have other primary malignancies within 5 years;
17. Known history of contraindications or hypersensitivity reactions to any investigational drug component or any known excipients
18. Women who are pregnant or breastfeeding.
19. Radiographic evidence of major blood vessel invasion/infiltration may be considered for enrollment if the investigator assesses that the risk is manageable.