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

NCT05024214 | Recruiting Phase 1

• 1 other identifier: KN035-CN-010
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 23

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.

Conditions

Solid Tumors; Non-small Cell Lung Cancer; Renal Cell Carcinoma; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Objective response rate (ORR) （Phase Ib）

  Two years

• Duration of response (DoR)

  Two years

• Progression Free Survival (PFS)

  Two years

• Overall Survival (OS)

  Two years

Other Outcomes (2)

• Disease control rate (DCR)

  Two years

• Time to Response(TTR)

  Two years

Study Arms (6)

Phase Ib arm

EXPERIMENTAL

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

Phase II cohort1-NSCLC

EXPERIMENTAL

Subjects with non-small cell lung cancer, resistant after previous treatment with PD-(L)1 inhibitors

Drug: Lenvatinib + Envafolimab

II Phase cohort1-RCC

EXPERIMENTAL

Subjects with renal cell carcinoma, resistant after previous treatment with PD-(L)1 inhibitors

Drug: Lenvatinib + Envafolimab

Phase II cohort1-HCC

EXPERIMENTAL

Subjects with hepatocellular carcinoma, resistant after previous treatment with PD-(L)1 inhibitors

Drug: Lenvatinib + Envafolimab

Phase II cohor2-experiment group

EXPERIMENTAL

Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease

Drug: Lenvatinib + Envafolimab

Phase II cohort2-control group

EXPERIMENTAL

Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease

Drug: Sunitinib

Interventions

Lenvatinib + Envafolimab DRUG

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.

II Phase cohort1-RCC; Phase II cohor2-experiment group; Phase II cohort1-HCC; Phase II cohort1-NSCLC; Phase Ib arm

Sunitinib DRUG

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.

Phase II cohort2-control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• 3D Medicines (Sichuan) Co., Ltd.: lead

Study Sites (23)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233004, China

RECRUITING

The Seventh Medical Center of the PLA General Hospital

Beijing, Beijing Municipality, 100700, China

RECRUITING

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

NOT YET RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

NOT YET RECRUITING

Zhongshan Hospital,Fudan University(Xiamen Branch)

Xiamen, Fujian, 361015, China

NOT YET RECRUITING

Dongguan People's Hospital

Dongguan, Guangdong, 523059, China

RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510280, China

RECRUITING

The Fifth Affiliated Hospital Sun Yat-Sen University

Zhuhai, Guangdong, 519000, China

RECRUITING

Harbin Medical University Cancer Hospital

Haerbin, Heilongjiang, 150081, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

The Second Affiliater Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

NOT YET RECRUITING

THE First Hospital of Jilin University

Changchun, Jilin, 130012, China

NOT YET RECRUITING

Jilin Cancer Hospital

Changchun, Jilin, 130028, China

NOT YET RECRUITING

The First Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, 116011, China

RECRUITING

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110001, China

RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110011, China

RECRUITING

The 960th Hospital of the PLA Joint Logistics Support Force

Jinan, Shandong, 250031, China

RECRUITING

First Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

The Cancer Affiliated Hospital of Xinjiang Medical College

Ürümqi, Xinjiang, 830011, China

RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650118, China

RECRUITING

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310020, China

RECRUITING

Fudan University

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Carcinoma, Hepatocellular

Interventions

lenvatinib; envafolimab; Sunitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Tianshu Liu

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

siying xu

CONTACT

+86(10) 64882533; siying.xu@3d-medicines.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2021
• First Posted: August 27, 2021
• Study Start: November 15, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

CN (23)