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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05024214
• Other study ID #: KN035-CN-010
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 15, 2021
• Est. completion date: June 2024

Study information

• Verified date: January 2024
• Source: 3D Medicines
• Contact: siying xu
• Phone: +86(10) 64882533
• Email: siying.xu[@]3d-medicines.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Hepatocellular Carcinoma
• Non-small Cell Lung Cancer
• Renal Cell Carcinoma
• Solid Tumors

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	The Seventh Medical Center of the PLA General Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Benbu	Anhui
China	Jilin Cancer Hospital	Changchun	Jilin
China	THE First Hospital of Jilin University	Changchun	Jilin
China	The First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Dongguan People's Hospital	Dongguan	Guangdong
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Harbin Medical University Cancer Hospital	Haerbin	Heilongjiang
China	Sir Run Run Shaw Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The 960th Hospital of the PLA Joint Logistics Support Force	Jinan	Shandong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	The Second Affiliater Hospital of Nanchang University	Nanchang	Jiangxi
China	Fudan University	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	The Cancer Affiliated Hospital of Xinjiang Medical College	Urumqi	Xinjiang
China	Zhongshan Hospital,Fudan University(Xiamen Branch)	Xiamen	Fujian
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	The Fifth Affiliated Hospital Sun Yat-Sen University	Zhuhai	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
3D Medicines (Sichuan) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Disease control rate (DCR)	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
Other	Time to Response(TTR)	Defined as the time from experiment drug administration to the first date of response was objectively documented	Two years
Primary	RP2D(Phase Ib)	Recommendation phase II dose	first Cycle (28 Days)
Primary	Dose Limiting Toxicity (DLT) (Phase Ib)	Number of participants who experience DLT of the first Cycle(28days)	first Cycle (28 Days)
Primary	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	Objective response rate (ORR) (Phase Ib)	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	Duration of response (DoR)	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
Secondary	Progression Free Survival (PFS)	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
Secondary	Overall Survival (OS)	Defined as the time from experiment drug administration to death due to any cause	Two years