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

Overview

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

• Drug Lenvatinib + 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.
• Drug Sunitinib
  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.

Primary outcome measures

• RP2D(Phase Ib) [Time frame: first Cycle (28 Days)]
• Dose Limiting Toxicity (DLT) (Phase Ib) [Time frame: first Cycle (28 Days)]
• objective response rate (ORR) （Phase II） [Time frame: Two years]

Secondary outcome measures (4)

• Objective response rate (ORR) （Phase Ib） [Time frame: Two years]
• Duration of response (DoR) [Time frame: Two years]
• Progression Free Survival (PFS) [Time frame: Two years]
• Overall Survival (OS) [Time frame: Two years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 23 centers

• The First Affiliated Hospital of Bengbu Medical College — Bengbu
• The Seventh Medical Center of the PLA General Hospital — Beijing
• Beijing Hospital — Beijing
• Fujian Medical University Union Hospital — Fuzhou
• Zhongshan Hospital,Fudan University(Xiamen Branch) — Xiamen
• Dongguan People's Hospital — Dongguan
• Zhujiang Hospital of Southern Medical University — Guangzhou
• The Fifth Affiliated Hospital Sun Yat-Sen University — Zhuhai
• … and 15 more centers

Identifiers

NCT: NCT05024214 · KN035-CN-010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗