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

NCT05306847 | Not Yet Recruiting Phase 2

• 1 other identifier: HS-3340
• Study Type: interventional
• Target: 93
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-small-cell lung cancer; Sintilimab; Anlotinib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Objective response rate (ORR)

  18 weeks from the initiation of the tested regime therapy

• R0 resection rate

  within 28 working days after operation

• Major pathological response rate

  within 28 working days after operation

• Pathological complete response rate

  within 28 working days after operation

• Overall survival (OS)

  2 years from the initiation of the tested regime therapy

Study Arms (1)

Experimental arm

EXPERIMENTAL

Sintilimab will be given intravenously at a dose of 200mg every 21 days. Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle. Tumor evaluation will be conducted after treatment of the tested regimen every 2 cycles. Subsequent treatment will be determined based on the evaluation results: If the patients are not suitable for radical surgery, but the result of efficacy evaluation is CR, PR, or SD, they can continue to receive the tested regimen. If the patients are still not suitable for radical surgery after 6 cycles of the tested regimen, the standard first-line or immunotherapy after chemoradiotherapy or radiotherapy will be given. If patients are eligible for radical surgery, surgery will be performed within 4 weeks after completion of the last tested regimen.

Drug: Sintilimab; Drug: Anlotinib

Interventions

Sintilimab DRUG

Sintilimab will be given intravenously at a dose of 200mg every 21 days.

Also known as: IBI308, Tyvyt

Experimental arm

Anlotinib DRUG

Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle.

Also known as: Anlotinib hydrochloride, AL3818

Experimental arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥18 years and ≤75 years.
• ECOG PS score: 0 to 1.
• The main organs function is normal, that is, the following criteria met:
• Good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L \[no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment\];
• 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;
• The oxygen saturation of the finger tip ≥ 92% both at rest and during walking (without oxygen inhalation).
• The life expectancy ≥12 weeks.
• Signed and dated informed consent.

You may not qualify if:

• 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.
• Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma.
• With driver mutation (EGFR/ALK/ROS1).
• With uncontrollable hypertension (systolic pressure \> 160 mmHg, diastolic pressure \> 100 mmHg) even receiving antihypertensive drug therapy.
• 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.
• Has an active infection requiring systemic therapy.
• 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.
• With immunodeficiency status, including but not limited to HIV infection and primary immunodeficiency diseases.
• Previously treated with ICIs.
• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Xinda Biopharmaceutical Group: collaborator
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Related Publications (8)

• 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).

  BACKGROUND

• Mery B, Guy JB, Swalduz A, Vallard A, Guibert C, Almokhles H, Ben Mrad M, Rivoirard R, Falk AT, Fournel P, Magne 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.

  PMID: 26095618 BACKGROUND

• 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, Ozguroglu 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.

  PMID: 33476803 BACKGROUND

• 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.

  PMID: 18718891 BACKGROUND

• 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.

  PMID: 33725921 BACKGROUND

• Eberhardt WE, Pottgen 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, Lutke-Brintrup D, Lehmann N, Schuler M, Jockel 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.

  PMID: 26527789 BACKGROUND

• 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.

  PMID: 34596079 BACKGROUND

• 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.

  PMID: 33524601 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sintilimab; anlotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chunmei Bai, Professor

  Peking union medical colloge hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yingyi Wang, Professor

CONTACT

+86 010-69158764; wangyingyi@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 1, 2022
• Study Start: April 1, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2026
• Last Updated: April 1, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 1 year of study completion
• Access Criteria: Data access requests will be reviewed by an external independent Review Panel. Requestors will be required to sign a Data Access Agreement