Sintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

Sintilimab Combined With Anlotinib Therapy for Patients With Initially Unresectable Stage II-III Non-small Cell Lung Cancer: A Prospective, Single-arm Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05306847
• Other study ID #: HS-3340
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2022
• Est. completion date: April 1, 2026

Study information

• Verified date: March 2022
• Source: Peking Union Medical College Hospital
• Contact: Yingyi Wang, Professor
• Phone: +86 010-69158764
• Email: wangyingyi[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Concurrent or sequential chemoradiotherapy has been recommended as the standard treatment for locally advanced and unresectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. PD-1/PD-L1 inhibitors have been proven to be effective for late-stage NSCLC, and anti-angiogenesis agents have also been used for the first-line treatment of advanced or metastatic NSCLC. Therefore, we designed this single-arm clinical trial, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC.

Description:

Concurrent or sequential chemoradiotherapy is the standard treatment for patients with locally advanced NSCLC, but patients receiving chemoradiotherapy have limited improvement in prognosis and are almost impossible to achieve a radical cure. Considering the excellent effect of immunotherapy and anti-angiogenesis therapy in NSCLC, we designed this single-arm clinical study, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC, in order to enable patients to achieve further surgical treatment and prolonged survival.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 93
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage II-III C) NSCLC confirmed by histology who are initially unable to undergo surgery and concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.

2. Age =18 years and =75 years.

3. ECOG PS score: 0 to 1.

4. The main organs function is normal, that is, the following criteria met:

1. Good hematopoietic function, defined as absolute neutrophil count =1.5×109 /L, platelet count=100 ×109 /L, hemoglobin =90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment];

2. Biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr =1.5×ULN or creatinine clearance (CCr) =60ml/min; Coagulation function is good, INR and PT =1.5 × ULN;

3. The oxygen saturation of the finger tip = 92% both at rest and during walking (without oxygen inhalation).

5. The life expectancy =12 weeks.

6. Signed and dated informed consent.

Exclusion Criteria:

1. Subjects at risk of massive hemoptysis or with blood in sputum, including but not limited to tumor lesions no more than 5 mm away from large vessels, tumors invading large vessels, and obvious lung cavity/necrotizing tumors.

2. Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma.

3. With driver mutation (EGFR/ALK/ROS1).

4. With uncontrollable hypertension (systolic pressure > 160 mmHg, diastolic pressure > 100 mmHg) even receiving antihypertensive drug therapy.

5. Has an active autoimmune disease, history of allogeneic stem cell transplantation or organ transplantation that has required systemic treatment. Replacement therapy is not considered a form of systemic treatment and is allowed.

6. Has an active infection requiring systemic therapy.

7. Has other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) or concomitant diseases that seriously endanger the patients or affect the patients completing the study at the same time.

8. With immunodeficiency status, including but not limited to HIV infection and primary immunodeficiency diseases.

9. Previously treated with ICIs.

10. Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• Sintilimab
Sintilimab will be given intravenously at a dose of 200mg every 21 days.
• Anlotinib
Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Xinda Biopharmaceutical Group

References & Publications (8)

Chu T, Zhong R, Zhong H, Zhang B, Zhang W, Shi C, Qian J, Zhang Y, Chang Q, Zhang X, Dong Y, Teng J, Gao Z, Qiang H, Nie W, Zhao Y, Han Y, Chen Y, Han B. Phase 1b Study of Sintilimab Plus Anlotinib as First-line Therapy in Patients With Advanced NSCLC. J Thorac Oncol. 2021 Apr;16(4):643-652. doi: 10.1016/j.jtho.2020.11.026. Epub 2021 Jan 29. — View Citation

De Ruysscher D, Botterweck A, Dirx M, Pijls-Johannesma M, Wanders R, Hochstenbag M, Dingemans AM, Bootsma G, Geraedts W, Simons J, Pitz C, Lambin P. Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prospective, population-based study. Ann Oncol. 2009 Jan;20(1):98-102. doi: 10.1093/annonc/mdn559. Epub 2008 Aug 20. — View Citation

Deng H, Liu J, Cai X, Chen J, Rocco G, Petersen RH, Brunelli A, Ng CSH, D'Amico TA, Liang W, He J. Radical Minimally Invasive Surgery After Immuno-chemotherapy in Initially-unresectable Stage IIIB Non-small cell Lung Cancer. Ann Surg. 2022 Mar 1;275(3):e600-e602. doi: 10.1097/SLA.0000000000005233. — View Citation

Eberhardt WE, Pöttgen C, Gauler TC, Friedel G, Veit S, Heinrich V, Welter S, Budach W, Spengler W, Kimmich M, Fischer B, Schmidberger H, De Ruysscher D, Belka C, Cordes S, Hepp R, Lütke-Brintrup D, Lehmann N, Schuler M, Jöckel KH, Stamatis G, Stuschke M. Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE). J Clin Oncol. 2015 Dec 10;33(35):4194-201. doi: 10.1200/JCO.2015.62.6812. Epub 2015 Nov 2. — View Citation

Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Özgüroglu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial. J Thorac Oncol. 2021 May;16(5):860-867. doi: 10.1016/j.jtho.2020.12.015. Epub 2021 Jan 19. — View Citation

Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick S, Brahmer J, Swanson SJ et al: Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment (tx) for resectable (IB-IIIA) non-small cell lung cancer (NSCLC) in the phase 3 CheckMate 816 trial. Cancer research 2021, 81(13 SUPPL).

Méry B, Guy JB, Swalduz A, Vallard A, Guibert C, Almokhles H, Ben Mrad M, Rivoirard R, Falk AT, Fournel P, Magné N. The evolving locally-advanced non-small cell lung cancer landscape: Building on past evidence and experience. Crit Rev Oncol Hematol. 2015 Nov;96(2):319-27. doi: 10.1016/j.critrevonc.2015.05.020. Epub 2015 Jun 7. Review. — View Citation

Xiao W, Hong M. Concurrent vs sequential chemoradiotherapy for patients with advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2021 Mar 19;100(11):e21455. doi: 10.1097/MD.0000000000021455. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Surgical conversion rate	The surgical conversion rate was defined as the proportion of subjects with the successful conversion over all subjects who received the tested regime.	18 weeks from the initiation of the tested regime therapy
Secondary	Objective response rate (ORR)	ORR is defined as the percentage of participants who have the best overall response (BOR) of complete response (CR) or partial response (PR) assessed based on RECIST 1.1.	18 weeks from the initiation of the tested regime therapy
Secondary	R0 resection rate	R0 resection rate is defined as the complete resection rate of all tumor under microscope.	within 28 working days after operation
Secondary	Major pathological response rate	Major pathological response rate is defined as the percentage of patients who achieved a major pathological response (residual tumor =10%).	within 28 working days after operation
Secondary	Pathological complete response rate	Pathological complete response rate is defined as the percentage of patients who achieved a pathological complete response (residual tumor = 0%).	within 28 working days after operation
Secondary	Overall survival (OS)	OS is measured from the time from the treatment onset (date of first study dose) until the date of death from any cause.	2 years from the initiation of the tested regime therapy
Secondary	Progression-free survival (PFS)	PFS is measured from the time from the treatment onset (date of first study dose) until the date of tumor progression or death from any cause.	2 years from the initiation of the tested regime therapy
Secondary	Disease-free survival (DFS)	DFS is measured from the time from radical surgery until the date of tumor progression or death from any cause.	2 years from the initiation of the tested regime therapy
Secondary	Treatment-related adverse events	Incidence and grade of treatment-related adverse events assessed based on CTCAE 5.0	3 months from the end of the tested regime therapy