Clinical trial NCT05024214: Phase Ib/II Trial of Envafolimab Plus Lenvatinib for Subjects With Solid Tumors
Official title: Envafolimab(KN035) in Combination With Lenvatinib in the Treatment of Advanced Solid Tumors: a Multicenter, Open-label, Phase Ib/II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Non-small Cell Lung Cancer
Renal Cell Carcinoma
Hepatocellular Carcinoma
Lead sponsor: 3D Medicines
Sponsor class: INDUSTRY
First posted: 2021-08-27
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: RP2D(Phase Ib)
timeFrame: first Cycle (28 Days)
measure: Dose Limiting Toxicity (DLT) (Phase Ib)
timeFrame: first Cycle (28 Days)
measure: objective response rate (ORR) （Phase II）
timeFrame: Two years
Secondary outcomes:
measure: Objective response rate (ORR) （Phase Ib）
timeFrame: Two years
measure: Duration of response (DoR)
timeFrame: Two years
measure: Progression Free Survival (PFS)
timeFrame: Two years
measure: Overall Survival (OS)
timeFrame: Two years
Other outcomes:
measure: Disease control rate (DCR)
timeFrame: Two years
measure: Time to Response(TTR)
timeFrame: Two years
Locations:
city: Benbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: The Seventh Medical Center of the PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: Zhongshan Hospital,Fudan University(Xiamen Branch)
state: Fujian
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University
state: Guangdong
city: Haerbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Nanchang
country: China
facility: The Second Affiliater Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: THE First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Jinan
country: China
facility: The 960th Hospital of the PLA Joint Logistics Support Force
state: Shandong
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Urumqi
country: China
facility: The Cancer Affiliated Hospital of Xinjiang Medical College
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Shanghai
country: China
facility: Fudan University
Study officials:
affiliation: Fudan University
name: Tianshu Liu
role: PRINCIPAL_INVESTIGATOR
References: