Consolidation Sintilimab After Concurrent Chemoradiation in Patients With Unresectable Stage III NSCLC

Phase 3

• Conditions: Carcinoma, Non-Small Cell Lung
• Interventions: Drug: Consolidation Sintilimab

• Registration Number: NCT03884192
• Lead Sponsor: Shandong Cancer Hospital and Institute

Brief Summary

This is an open label, multi-center, randomized, control phase III trial, to compare the efficacy and safety of consolidation therapy with sintilimab (IBI308) versus best supported care (BSC), in unresectable stage III NSCLC patients who do not experience disease progression after initial concurrent chemoradiation.

Detailed Description

This is an open label, multi-center, randomized, control study of sintilimab versus BSC in unresectable local advanced stage III NSCLC patients without disease progression after concurrent chemoradiation.

Study Timeline

• Study Start: 2018-12-12
• Study First Submitted: 2019-01-11
• Status Verified: 2019-03
• Study First Submitted QC: 2019-03-19
• Last Update Submitted: 2019-03-19
• Study First Posted: 2019-03-21
• Last Update Posted: 2019-03-21
• Primary Completion: 2020-12-30
• Study Completion: 2021-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

1. Signed written informed consent before initiation of any study procedures
2. Age ≥ 18 years and ≤ 75 years
3. Histologically or cytologically confirmed NSCLC, with unresectable local advanced disease (stage III according to NSCLC staging version 8)
4. Expected survival over 3 months
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. At least 1 measurable disease according to RECIST 1.1
7. Pulmonary function: forced expiratory volume at one second (FEV1) > 1 liter(L)
8. Patient must not have received any anti-cancer therapy for the purpose of treating lung cancer. However, exploratory thoracotomy, mediastinoscopy, excision biopsy, and other kinds of surgery for diagnosis and staging purpose is acceptable. Patients with local or regional recurrent disease after pneumonectomy is allowed to participate if they meet other inclusion criteria (e.g. stage III, inappropriate for re-operation).
9. For all female patients of childbearing potential, a negative pregnancy test (either urine or serum) must be obtained within 3 days before the first dose (Cycle 1, Day 1) of study treatment. If a urine pregnancy test shows an unconfirmed result, a serum pregnancy test must be performed.
10. Adequate hematopoietic function, defined as: absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L; platelet count ≥100 x 10*9/L; hemoglobin ≥90 g/L [no blood transfusion within 7 days or not erythropoietin (EPO) dependent]
11. Adequate liver function, defined as: total serum bilirubin ≤ 1.5 x upper limit of normal (ULN); serum alanine transaminase (ALT) and aspartic transaminase (AST) ≤ 2.5 x ULN, with no liver transplantation
12. Adequate renal function, defined as: serum creatinine ≤ 1.5 x ULN or calculated creatinine-clearance ≥ 60 ml/min (Cockcroft-Gault). Urine protein less than 2+ by urinalysis or 24-hour urinary protein quantity < 1g
13. Adequate coagulation function, defined as: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN. For patients receiving anticoagulant therapy can be enrolled if PT is within the range defined by anticoagulant therapy.
14. Myocardial enzymes are within normal range
15. All subjects of childbearing potential must agree to use efficient contraceptive methods that result in a failure rate of < 1% per year during the study treatment period and for at least 180 days after discontinuation from study treatment.

Exclusion Criteria

1. Being treated by other investigational drugs within an interventional study, or have received any investigational drugs or instruments within 4 weeks prior to the first dose of study treatment

2. Being enrolled in other interventional studies, unless they are observational studies or during the follow-up stage of an interventional study

3. NSCLC histology with small cell lung cancer (SCLC) components

4. Active or autoimmune disease history (within the past 2 years), or history of immune deficiency

5. Previous immune therapy including: anti PD-1, anti PD-L1, anti PD-L2 or treatment targeting other co-stimulatory or co-inhibitory T-cell receptors [e.g. cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, and CD137]

   a) Systemic therapy with Chinese patent medicine or drugs of immunoregulation effect (including thymosin, interferon, interleukin, unless local delivery for controlling pleural effusion) within 2 weeks prior to the first dose of study treatment, or major surgery within 4 weeks prior to the first dose of study treatment

6. Clinical evidence of active diverticulitis, abdominal abscess, or gastrointestinal obstruction

7. Previous organ or blood system transplantation

8. Known allergic to pemetrexed, paclitaxel, etoposide, cisplatin, carboplatin, sintilimab component and/or any excipients

9. A history of active autoimmune disease requiring systemic treatment (e.g. using drugs for disease remission, corticosteroids or immunosuppressor) within 2 years prior to the first dose of study treatment. Substitution therapy (e.g. thyroxine, insulin or physiological corticosteroids for treating adrenal or pituitary dysfunction) is not considered as a systemic treatment.

   a) Diagnosis as immunodeficiency, or being treated with systemic glucocorticoid or other kinds of immunosuppressor within 7 days prior to the first dose of study treatment. A physiological dose of glucocorticoid (≤10 mg/day prednisone or equivalent dose of other steroids) is permitted.

10. Previously diagnosis as other malignant tumors within 5 years prior to the first dose of study treatment, with the exception of: skin basal cell carcinoma or squamous cell carcinoma with radical treatment, and/or carcinoma in situ underwent radical resection

11. History of non-infectious pneumonitis requiring treatment with glucocorticoid within 1 year prior to the first dose of study treatment, or currently existed interstitial lung disease

12. Active infectious that required systemic therapy

13. Know psychiatric illness or drug abuse that would limit compliance with study requirements

14. Know human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive)

15. Untreated active viral hepatitis B (HBV)

    Patients with HBV who meet the following criteria are also eligible:

    1. HBV virus load (VL) <1000 copy/ml (200 IU/ml), and patients must continuously receive anti-HBV therapy during all through study treatment phase to prevent virus activation
    2. Patients with a result of anti-HBc(+)、HBsAg (-)、anti-HBs (-) 和 HBV VL (-) are not required to receive prophylactic anti-HBV therapy, but must be closely monitored for virus re-activation

16. Patients with active HCV infection (HCV antibody positive and HCV-RNA > the lower detection limit)

17. History or evidence of disease, treatment or laboratory abnormalities that would interfere the study outcome, prevent patients from participating entirely, or ineligible to enroll per the investigators' judgement

18. Pregnant or lactating women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sintilimab Arm	Consolidation Sintilimab	Sintilimab consolidation therapy

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	up to 24 months after enrollment or study close	PFS (per RECIST 1.1 as assessed by the investigator) will be defined as the time from the date of randomisation until the date of objective disease progression or death (by any cause in the absence of progression).

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	up to 24 months after enrollment or study close	OS (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date of randomisation until death due to any cause.
Objective Response Rate (ORR)	up to 24 months after enrollment or study close	ORR (per RECIST 1.1 as assessed by the investigator) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).
Disease Control Rate (DCR)	up to 24 months after enrollment or study close	DCR (per RECIST 1.1 as assessed by the investigator) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR), or stable disease (SD).
Duration of Response (DoR)	up to 24 months after enrollment or study close	DoR (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) until the date for the first documented response of progressive disease (PD) or death in the absence of progression.
Progression Free Survival (PFS) Rate at 12/18 months	From the date of randomization until the Kaplan-Meier estimate of PFS at 12/18months	PFS rate at 12/18 months is defined as the proportion (%) of patients who are alive and progression free at 12 and 18months from the date of randomisation.
Treatment-related Adverse Events (AEs)	From the date of randomization to 90 days after last dose of study treatment	The grade of AEs and the number of patients with AEs are assessed by the investigator based on CTCAE v4.03 from the date of randomization to 90 days after last dose of study treatment.

Trial Locations

Locations (1)

Shandong Cancer Hospital; 🇨🇳 Jinan, Shandong, China