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

Official title

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

Overview

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.

Interventions

• 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

Primary outcome measures

• major pathological response (MPR) [Time frame: 10 days postoperatively]

Secondary outcome measures (5)

• pathological complete response (pCR) [Time frame: 10 days postoperatively]
• treatment-related adverse events (TRAEs) [Time frame: 90 days after the last dose of study drugs]
• disease-free survival (DFS) [Time frame: 5 years]
• rate of operative complications [Time frame: 30 days postoperatively]
• overall survival(OS) [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Providing written informed consent prior to initiating the study.
• Regardless of sex, aged ≥18 years and ≤75 years.
• Histologically confirmed NSCLC.
• At least one radiologically measureable lesion according to response evaluation criteria in solid tumors version 1.1(RECIST V1.1).
• Treatment-naïve IB-IIIB resectable NSCLC (American Joint Committee on Cancer 8th tumor-node-metastasis classification).
• Epidermal growth factor receptor(EFGR)/anaplastic lymphoma kinase(ALK)/ROS proto-oncogene 1(ROS1) wild type NSCLC.
• Absence of bleeding risk.
• Consent to surgical treatment.
• Indication for surgery confirmed by surgeons.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Expected survival time more than 6 months.
• 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)
• 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.
• 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：

• 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.
• 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.
• 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).
• 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).
• 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.
• 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.
• 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.
• Undergoing allogeneic organ transplant (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplant.
• Allergy to the active ingredient or excipients of the study drug, sintilimab.
• 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)
• Known history of human immunodeficiency virus (HIV) infection.
• 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).
• Active hepatitis C infection.
• Receiving a live vaccine within 30 days prior to the first dose of the study drug.
• Pregnant or lactating women.
• Other investigator's defined uncontrolled systemic disease.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06221462 · NBEY-HS-2023-008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗