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

March 23, 2026 updated by: 3D Medicines (Sichuan) Co., Ltd.

Envafolimab(KN035) in Combination With Lenvatinib in the Treatment of Advanced Solid Tumors: a Multicenter, Open-label, Phase Ib/II Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

170

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Fudan University
        • Contact:
          • Tianshu Liu
    • Anhui
      • Bengbu, Anhui, China, 233004
        • Recruiting
        • The first affiliated hospital of bengbu medical college
        • Contact:
        • Contact:
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100730
        • Not yet recruiting
        • Beijing Hospital
        • Contact:
        • Contact:
      • Beijing, Beijing Municipality, China, 100700
        • Recruiting
        • The Seventh Medical Center of the PLA General Hospital
        • Contact:
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China, 350001
        • Not yet recruiting
        • Fujian Medical University Union Hospital
        • Contact:
        • Contact:
      • Xiamen, Fujian, China, 361015
        • Not yet recruiting
        • Zhongshan Hospital,Fudan University(Xiamen Branch)
        • Contact:
        • Contact:
    • Guangdong
      • Dongguan, Guangdong, China, 523059
        • Recruiting
        • Dongguan People's Hospital
        • Contact:
        • Contact:
      • Guangzhou, Guangdong, China, 510280
        • Recruiting
        • Zhujiang Hospital of Southern Medical University
        • Contact:
        • Contact:
      • Zhuhai, Guangdong, China, 519000
        • Recruiting
        • The Fifth Affiliated Hospital Sun Yat-Sen University
        • Contact:
          • Pengfei Pang 0756-2528188
          • Phone Number: 0756-2528188
          • Email: zdwygcp@126.com
        • Contact:
    • Heilongjiang
      • Haerbin, Heilongjiang, China, 150081
        • Not yet recruiting
        • Harbin Medical University Cancer Hospital
        • Contact:
        • Contact:
    • Henan
      • Zhengzhou, Henan, China, 450052
        • Recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China, 330006
        • Not yet recruiting
        • The Second Affiliater Hospital of Nanchang University
        • Contact:
        • Contact:
    • Jilin
      • Changchun, Jilin, China, 130012
        • Not yet recruiting
        • The First Hospital of Jilin University
        • Contact:
        • Contact:
      • Changchun, Jilin, China, 130028
        • Not yet recruiting
        • Jilin Cancer Hospital
        • Contact:
        • Contact:
    • Liaoning
      • Dalian, Liaoning, China, 116011
        • Recruiting
        • The First Affiliated Hospital of Dalian Medical University
        • Contact:
        • Contact:
      • Shenyang, Liaoning, China, 110001
        • Recruiting
        • Shengjing Hospital of China Medical University
        • Contact:
      • Shenyang, Liaoning, China, 110011
        • Recruiting
        • Liaoning Cancer Hospital & Institute
        • Contact:
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250031
        • Recruiting
        • The 960th Hospital of the PLA Joint Logistics Support Force
        • Contact:
        • Contact:
    • Shanxi
      • Taiyuan, Shanxi, China, 030001
        • Recruiting
        • First Hospital of Shanxi Medical University
        • Contact:
        • Contact:
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300060
        • Recruiting
        • Tianjin Medical University Cancer Institute & Hospital
        • Contact:
        • Contact:
    • Xinjiang
      • Ürümqi, Xinjiang, China, 830011
        • Recruiting
        • The Cancer Affiliated Hospital of Xinjiang Medical College
        • Contact:
        • Contact:
    • Yunnan
      • Kunming, Yunnan, China, 650118
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310020
        • Recruiting
        • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase Ib arm
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

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.
Experimental: Phase II cohort1-NSCLC
Subjects with non-small cell lung cancer, resistant after previous treatment with PD-(L)1 inhibitors
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.
Experimental: II Phase cohort1-RCC
Subjects with renal cell carcinoma, resistant after previous treatment with PD-(L)1 inhibitors
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.
Experimental: Phase II cohort1-HCC
Subjects with hepatocellular carcinoma, resistant after previous treatment with PD-(L)1 inhibitors
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.
Experimental: Phase II cohor2-experiment group
Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease
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.
Experimental: Phase II cohort2-control group
Subjects with renal cell carcinoma, no previous systemic treatment for advanced disease
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RP2D(Phase Ib)
Time Frame: first Cycle (28 Days)
Recommendation phase II dose
first Cycle (28 Days)
Dose Limiting Toxicity (DLT) (Phase Ib)
Time Frame: first Cycle (28 Days)
Number of participants who experience DLT of the first Cycle（28days)
first Cycle (28 Days)
objective response rate (ORR) （Phase II）
Time Frame: 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.
Two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) （Phase Ib）
Time Frame: 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.
Two years
Duration of response (DoR)
Time Frame: 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.
Two years
Progression Free Survival (PFS)
Time Frame: 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.
Two years
Overall Survival (OS)
Time Frame: Two years
Defined as the time from experiment drug administration to death due to any cause
Two years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate (DCR)
Time Frame: Two years
Defined as the percentage of participants in the analysis population who experienced a Complete Response or a Partial Response or stable disease and was assessed using RECIST 1.1 based on investigato evaluation
Two years
Time to Response(TTR)
Time Frame: Two years
Defined as the time from experiment drug administration to the first date of response was objectively documented
Two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

3D Medicines (Sichuan) Co., Ltd.

Investigators

  • Principal Investigator: Tianshu Liu, Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2021

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

August 15, 2021

First Submitted That Met QC Criteria

August 22, 2021

First Posted (Actual)

August 27, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2026

Last Update Submitted That Met QC Criteria

March 23, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KN035-CN-010

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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