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

March 23, 2022 updated by: YueJuan Cheng, Peking Union Medical College Hospital

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

93

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental arm

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
Sintilimab will be given intravenously at a dose of 200mg every 21 days.
Other Names:
  • IBI308
  • Tyvyt
Drug: Anlotinib
Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle.
Other Names:
  • AL3818
  • Anlotinib hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Surgical conversion rate
Time Frame: 18 weeks from the initiation of the tested regime therapy
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 18 weeks from the initiation of the tested regime therapy
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
R0 resection rate
Time Frame: within 28 working days after operation
R0 resection rate is defined as the complete resection rate of all tumor under microscope.
within 28 working days after operation
Major pathological response rate
Time Frame: within 28 working days after operation
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
Pathological complete response rate
Time Frame: within 28 working days after operation
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
Overall survival (OS)
Time Frame: 2 years from the initiation of the tested regime therapy
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
Progression-free survival (PFS)
Time Frame: 2 years from the initiation of the tested regime therapy
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
Disease-free survival (DFS)
Time Frame: 2 years from the initiation of the tested regime therapy
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
Treatment-related adverse events
Time Frame: 3 months from the end of the tested regime therapy
Incidence and grade of treatment-related adverse events assessed based on CTCAE 5.0
3 months from the end of the tested regime therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Xinda Biopharmaceutical Group

Investigators

  • Principal Investigator: Chunmei Bai, Professor, Peking union medical colloge hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

April 1, 2022

Primary Completion (Anticipated)

April 1, 2024

Study Completion (Anticipated)

April 1, 2026

Study Registration Dates

First Submitted

March 21, 2022

First Submitted That Met QC Criteria

March 23, 2022

First Posted (Actual)

April 1, 2022

Study Record Updates

Last Update Posted (Actual)

April 1, 2022

Last Update Submitted That Met QC Criteria

March 23, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-3340

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data for all primary and secondary outcome measures will be made available.

IPD Sharing Time Frame

Data will be available within 1 year of study completion

IPD Sharing Access Criteria

Data access requests will be reviewed by an external independent Review Panel. Requestors will be required to sign a Data Access Agreement

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe