Hepatocellular Carcinoma, Non-small Cell Lung Cancer, Renal Cell Carcinoma, Solid Tumors
Conditions
Brief summary
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.
Interventions
DRUGLenvatinib + Envafolimab
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.
DRUGSunitinib
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.
Sponsors
3D Medicines (Sichuan) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP2D(Phase Ib) | first Cycle (28 Days) | Recommendation phase II dose |
| Dose Limiting Toxicity (DLT) (Phase Ib) | first Cycle (28 Days) | Number of participants who experience DLT of the first Cycle（28days) |
| objective response rate (ORR) （Phase II） | Two years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) （Phase Ib） | Two years | 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. |
| Duration of response (DoR) | Two years | 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. |
| Progression Free Survival (PFS) | Two years | 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. |
| Overall Survival (OS) | Two years | Defined as the time from experiment drug administration to death due to any cause |
Countries
China
Contacts
CONTACTsiying xu
PRINCIPAL_INVESTIGATORTianshu Liu
Fudan University
Outcome results
None listed