Neoadjuvant Sintilimab Plus Anlotinib Therapy in IB-IIIB Resectable Non-small Cell Lung Cancer (PRIORITY)

Neoadjuvant Sintilimab Plus Anlotinib Therapy in IB-IIIB Resectable Non-small Cell Lung Cancer (PRIORITY): a Prospective Single Center, Open Label, Phase II Study

This is a prospective single-center, open-label, phase II study evaluating the efficacy of sintilimab plus anlotinib as a neoadjuvant regimen in the treatment of IB-IIIB resectable non-small cell lung cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Sintilimab; Drug: Anlotinib

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fajiu Wang, PhD; Phone Number: +86-574-83870605; Email: wfjwyt@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Providing written informed consent prior to initiating the study.
2. Regardless of sex, aged ≥18 years and ≤75 years.
3. Histologically confirmed NSCLC.
4. At least one radiologically measureable lesion according to response evaluation criteria in solid tumors version 1.1(RECIST V1.1).
5. Treatment-naïve IB-IIIB resectable NSCLC (American Joint Committee on Cancer 8th tumor-node-metastasis classification).
6. Epidermal growth factor receptor(EFGR)/anaplastic lymphoma kinase(ALK)/ROS proto-oncogene 1(ROS1) wild type NSCLC.
7. Absence of bleeding risk.
8. Consent to surgical treatment.
9. Indication for surgery confirmed by surgeons.
10. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
11. Expected survival time more than 6 months.
12. Sufficient organ reserve, detailed as follows:(1) the absolute neutrophil count ≥1.5×109/L without the use of granulocyte colony-stimulating factor for the past 14 days prior to the first dose of study drugs;(2) platelet count ≥100×109/L without blood transfusion within the 2 weeks before the enrollment;(3) hemoglobin >9g/dL without recent usage of blood transfusion 14 days prior to the study;(4) total bilirubin ≤ 1.5 fold the upper limit of normal (ULN), or total bilirubin >1.5 fold ULN but direct bilirubin ≤ 1 fold ULN;(5) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN;(6) blood creatinine ≤ 1.5 fold ULN and creatinine clearance (calculated by the Cockcroft-Gault formula) ≥ 60ml/min;(7) adequate coagulation function, defined by international normalized ratio (INR) or prothrombin time(PT) less than 1.5 fold ULN;(8) normal thyroid function defined by the normal range of thyroid-stimulating hormone (TSH); otherwise, abnormal level of TSH with normal range of T3(or Ft3) and Ft4;(8) cardiac enzyme profile within the normal limits (merely laboratory abnormity without clinical significance based on investigator's decision is allowed)
13. For female participants of childbearing age, a urine or serum pregnancy test should be performed within 3 days before receiving the first dose of the study drugs, and the result must be negative. If the urine pregnancy test result is inconclusive, a blood pregnancy test is warranted. Postmenopausal women are defined as those who have been without menstruation for at least 1 year, or have undergone surgical sterilization or hysterectomy.
14. In the presence of pregnancy risk, all participants (both male and female) are required to use contraceptive measures with an annual failure rate of less than 1% throughout the entire treatment period up to 120 days following the last dose of the study drugs.

Exclusion Criteria:

Exclusion criteria as follows：

1. Other malignancy rather than NSCLC diagnosed within 5 years prior to the first dose of the study given, except for definitively treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma.
2. Enrolled in an ongoing interventional clinical trial, or receiving other study drugs or study medical devices within 4 weeks prior to the first dose of this study drugs.
3. A history of receiving the following therapies: anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death ligand-1 (anti-PD-L1) or anti-programmed cell death ligand-2 (anti-PD-L2) drugs, or drugs targeting T cell receptor (such as cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor receptor superfamily member 4 and CD137).
4. A history of receiving targeted therapy such as anti-vascular endothelial growth receptor (VEGR)/ vascular endothelial growth factor receptor (VEGFR), rapidly accelerated fibrosarcoma(RAF), mitogen-activated protein kinase(MAPK), platelet-derived growth factor Receptor(PDGFR) or fibroblast growth factor receptor(FGFR).
5. Receiving traditional Chinese medication or immunomodulatory drugs (including thymopentin, interferon, interleukin, except for controlling pleural effusion) as systemic therapy within 2 weeks prior to the first dose of the study drugs.
6. Active systemic auto-immune disease requiring systemic treatment within 2 years prior to the first dose of the study drugs, such as the use of disease-modifying drugs, glucocorticoids or immunosuppressants. Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered as systemic treatment.
7. Systemic glucocorticoid therapy (excluding nasal, inhaled or other local routes of glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs.
8. Undergoing allogeneic organ transplant (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplant.
9. Allergy to the active ingredient or excipients of the study drug, sintilimab.
10. Having not recovered from any toxicities and/or complications caused by prior interventions before the initiation of the study (i.e., ≤ Grade 1 or to baseline, excluding fatigue or hair loss)
11. Known history of human immunodeficiency virus (HIV) infection.
12. Untreated active hepatitis B (defined as hepatitis B surface antigen positive with detectable hepatitis B virus(HBV)-DNA copies exceeding the upper limit of normal values).
13. Active hepatitis C infection.
14. Receiving a live vaccine within 30 days prior to the first dose of the study drug.
15. Pregnant or lactating women.
16. Other investigator's defined uncontrolled systemic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment arm	Drug: Sintilimab; 200mg, every 3 weeks, 3 cycles, in the neoadjuvant setting, and adjuvant 200mg,every 3 weeks no more than one year; Drug: Anlotinib; 8mg, orally, D1-14, every 3 weeks, 2 cycles in only neoadjuvant setting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major pathological response (MPR)	Viable tumor cells are no more than 10% in the resected specimen	10 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete response (pCR)	Viable tumor cells are not found in the resected specimen	10 days postoperatively
treatment-related adverse events (TRAEs)	TRAEs including immune-related adverse reaction are documented and graded based on the US National Cancer Institute's Common Terminology Criteria for Adverse Events 5.0 criteria.	90 days after the last dose of study drugs
disease-free survival (DFS)	DFS is defined as the duration between the date of surgery and the date on which tumor recurrence is confirmed	5 years
overall survival(OS)	OS is defined as the duration between the date of surgery and the date of all-cause death	5 years
rate of operative complications	The rate of surgical complications (such as bleeding, bronchopleural fistula,ect) are recorded and graded according to Clavien-Dindo criteria	30 days postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
minimal residual disease (MRD)	MRD is evaluated by testing circulating tumor DNA (ctDNA) in peripheral blood sample using next-generation sequencing(NGS) method. Each participant will undergo a minium of 3 tests for MRD.	5 years

Collaborators and Investigators

• Sponsor: Ningbo No.2 Hospital
• Investigators: Principal Investigator: Guofang Zhao, MD, Ningbo No.2 Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: January 13, 2024
• First Posted (Actual): January 24, 2024

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: neoadjuvant therapy; Sintilimab; non small cell lung cancer; Anlotinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NBEY-HS-2023-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No