Phase Ib/II Trial of Envafolimab Plus Lenvatinib for Subjects With Solid Tumors
- Conditions
- Solid TumorsRenal Cell CarcinomaNon-small Cell Lung CancerHepatocellular Carcinoma
- Interventions
- Registration Number
- NCT05024214
- Lead Sponsor
- 3D Medicines (Sichuan) Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase II cohort1-NSCLC Lenvatinib + Envafolimab Subjects with non-small cell lung cancer, resistant after previous treatment with PD-(L)1 inhibitors II Phase cohort1-RCC Lenvatinib + Envafolimab Subjects with renal cell carcinoma, resistant after previous treatment with PD-(L)1 inhibitors Phase Ib arm Lenvatinib + Envafolimab 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 Phase II cohor2-experiment group Lenvatinib + Envafolimab Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease Phase II cohort1-HCC Lenvatinib + Envafolimab Subjects with hepatocellular carcinoma, resistant after previous treatment with PD-(L)1 inhibitors Phase II cohort2-control group Sunitinib Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Overall Survival (OS) Two years Defined as the time from experiment drug administration to death due to any cause
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.
Trial Locations
- Locations (23)
THE First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
The Cancer Affiliated Hospital of Xinjiang Medical College
🇨🇳Urumqi, Xinjiang, China
Yunnan Cancer Hospital
🇨🇳Kunming, Yunnan, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Benbu, Anhui, China
The Seventh Medical Center of the PLA General Hospital
🇨🇳Beijing, Beijing, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Zhongshan Hospital,Fudan University(Xiamen Branch)
🇨🇳Xiamen, Fujian, China
Zhujiang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Dongguan People's Hospital
🇨🇳Dongguan, Guangdong, China
The Fifth Affiliated Hospital Sun Yat-Sen University
🇨🇳Zhuhai, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Haerbin, Heilongjiang, China
The Second Affiliater Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
The First Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, Liaoning, China
The 960th Hospital of the PLA Joint Logistics Support Force
🇨🇳Jinan, Shandong, China
Fudan University
🇨🇳Shanghai, China
First Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China