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

Study Overview
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Brief Summary
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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.

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

Conditions
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Solid Tumors, Non-small Cell Lung Cancer, Renal Cell Carcinoma, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Lenvatinib + Envafolimab
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen years and older; 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; 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; phase II cohort 2：Unresectable locally advanced or metastatic or recurrent RCC; 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; 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； Life expectancy of at least 12 weeks; At least one measurable lesion per RECIST 1.1; Adequate organ function; Signed informed consent. Exclusion Criteria: Prior anticancer treatment within 4 weeks prior to the first dose of study drugs; Toxicity from prior anticancer therapy prior to the first dose of study drugs not recovered to ≤ grade1; Hypertension did not satisfactory controlled after antihypertensive medication Phase Ib/II: Subjects who were previously treated with Lenvatinib or who participated in a clinical trial of a generic version of Lenvatinib 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; Uncontrollable or significant cardiovascular or cerebrovascular disease; Active, known history or suspected autoimmune disease; 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; 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; Subjects with known or suspected interstitial pneumonia; 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) Active hepatitis B or hepatitis C; Known history of severe gastrointestinal bleeding or active hemoptysis or other severe bleeding within 6 months prior to first study drug therapy; Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage ; Known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis; Have other primary malignancies within 5 years; Known history of contraindications or hypersensitivity reactions to any investigational drug component or any known excipients Women who are pregnant or breastfeeding. Radiographic evidence of major blood vessel invasion/infiltration may be considered for enrollment if the investigator assesses that the risk is manageable.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase Ib arm<br>Subjects with advanced or metastatic solid tumor (excluding hepatocellular carcinoma and thyroid cancer) with disease progression or intolerance or no effective treatment after standard therapy | Drug: Lenvatinib + Envafolimab<br>* Lenvatinib will be administered with water orally once a day (with or without food) continuously in 28-day treatment cycle. Envafolimab, 400 mg per dose, subcutaneous injection, dosed on D1 and then D15 of Treatment Cycle 1, and D1 of Treatment Cycle 2 and every subsequent cycles, with every 28 days as one treatment cycle.<br>|
| Experimental: Phase II cohort1-NSCLC<br>Subjects with non-small cell lung cancer, resistant after previous treatment with PD-(L)1 inhibitors | Drug: Lenvatinib + Envafolimab<br>* Lenvatinib will be administered with water orally once a day (with or without food) continuously in 28-day treatment cycle. Envafolimab, 400 mg per dose, subcutaneous injection, dosed on D1 and then D15 of Treatment Cycle 1, and D1 of Treatment Cycle 2 and every subsequent cycles, with every 28 days as one treatment cycle.<br>|
| Experimental: II Phase cohort1-RCC<br>Subjects with renal cell carcinoma, resistant after previous treatment with PD-(L)1 inhibitors | Drug: Lenvatinib + Envafolimab<br>* Lenvatinib will be administered with water orally once a day (with or without food) continuously in 28-day treatment cycle. Envafolimab, 400 mg per dose, subcutaneous injection, dosed on D1 and then D15 of Treatment Cycle 1, and D1 of Treatment Cycle 2 and every subsequent cycles, with every 28 days as one treatment cycle.<br>|
| Experimental: Phase II cohort1-HCC<br>Subjects with hepatocellular carcinoma, resistant after previous treatment with PD-(L)1 inhibitors | Drug: Lenvatinib + Envafolimab<br>* Lenvatinib will be administered with water orally once a day (with or without food) continuously in 28-day treatment cycle. Envafolimab, 400 mg per dose, subcutaneous injection, dosed on D1 and then D15 of Treatment Cycle 1, and D1 of Treatment Cycle 2 and every subsequent cycles, with every 28 days as one treatment cycle.<br>|
| Experimental: Phase II cohor2-experiment group<br>Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease | Drug: Lenvatinib + Envafolimab<br>* Lenvatinib will be administered with water orally once a day (with or without food) continuously in 28-day treatment cycle. Envafolimab, 400 mg per dose, subcutaneous injection, dosed on D1 and then D15 of Treatment Cycle 1, and D1 of Treatment Cycle 2 and every subsequent cycles, with every 28 days as one treatment cycle.<br>|
| Experimental: Phase II cohort2-control group<br>Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease | Drug: Sunitinib<br>* Sunitinib will be administered with water orally once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off (Schedule 4/2) in 42-day treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RP2D(Phase Ib) | Recommendation phase II dose | first Cycle (28 Days) | 
| Dose Limiting Toxicity (DLT) (Phase Ib) | Number of participants who experience DLT of the first Cycle（28days) | first Cycle (28 Days) | 
| objective response rate (ORR) （Phase II） | Defined as the percentage of participants in the analysis population who experienced a Complete Response or a Partial Response and was assessed using RECIST 1.1 based on investigator evaluation. | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) （Phase Ib） | Defined as the percentage of participants in the analysis population who experienced a Complete Response or a Partial Response and was assessed using RECIST 1.1 based on investigator evaluation. | Two years | 
| Duration of response (DoR) | Defined as the time from response to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on investigator evaluation. | Two years | 
| Progression Free Survival (PFS) | Defined as the time from experiment drug administration to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on investigato evaluation. | Two years | 
| Overall Survival (OS) | Defined as the time from experiment drug administration to death due to any cause | Two years |