Neoadjuvant and Adjuvant Therapy Studies of Sindilizumab in Resectable Lung Cancer

Sponsor

Innovent Biologics (Suzhou) Co. Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05116462

Collaborator

(none)

800

Enrollment

Location

Arms

55.3

Anticipated Duration (Months)

14.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a multi-regional, randomized, double-blind Phase 3 study to compare the efficacy and safety of sintilimab plus chemotherapy (sintilimab combination) vs placebo plus chemotherapy (placebo combination) before surgery and sintilimab vs placebo after surgery in treatment-naive subjects with resectable Stage IIB (primary tumor > 4 cm) to IIIB (resectable N2 only) non-small cell lung cancer (NSCLC).

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer (NSCLC)	Drug: Sintilimab Drug: Carboplatin Drug: Nab-paclitaxel Drug: Cisplatin Drug: Pemetrexed Drug: Docetaxel Drug: Paclitaxel Drug: Gemcitabine Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Multi-Regional, Randomized, Double-blind, Phase 3 Study of the Efficacy and Safety of Sintilimab Plus Chemotherapy vs Placebo Plus Chemotherapy Before Surgery and Sintilimab vs Placebo After Surgery for Resectable Non-small Cell Lung Cancer

Anticipated Study Start Date :

Nov 11, 2021

Anticipated Primary Completion Date :

Aug 18, 2023

Anticipated Study Completion Date :

Jun 20, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sintilimab Neoadjuvant Treatment period: up to 3 cycles of sintilimab plus platinum-based chemotherapy prior to surgery. adjuvant Treatment period: Subjects will receive sintilimab therapy after surgery until disease recurrence, unacceptable toxicity, receiving new anti-tumor therapy, withdrawal of informed consent (ICF), lost to follow-up or death, or other conditions that require treatment discontinuation (whichever occurs first). The maximum duration of postoperative treatment with either sintilimab or placebo is 1 year.	Drug: Sintilimab 200 mg D1 IV Q3W Drug: Carboplatin AUC 5 or 6 mg/ml/min D1 IV Q3W Drug: Nab-paclitaxel 100 mg/m2 D1, 8, 15 IV Q3W Drug: Cisplatin 75 mg/m2 D1 IV Q3W Drug: Pemetrexed 500 mg/m2 D1 IV Q3W Drug: Docetaxel 60 or 75 mg/m2 D1 IV Q3W Drug: Paclitaxel 175 or 200 mg/m2 D1 IV Q3W Drug: Gemcitabine 1000 mg/m2 or 1250 mg/m2 D1, 8 IV Q3W
Placebo Comparator: Placebo Neoadjuvant Treatment period: up to 3 cycles of placebo plus platinum-based chemotherapy prior to surgery. adjuvant Treatment period: Subjects will receive placebo therapy after surgery until disease recurrence, unacceptable toxicity, receiving new anti-tumor therapy, withdrawal of informed consent (ICF), lost to follow-up or death, or other conditions that require treatment discontinuation (whichever occurs first). The maximum duration of postoperative treatment with either sintilimab or placebo is 1 year.	Drug: Carboplatin AUC 5 or 6 mg/ml/min D1 IV Q3W Drug: Nab-paclitaxel 100 mg/m2 D1, 8, 15 IV Q3W Drug: Cisplatin 75 mg/m2 D1 IV Q3W Drug: Pemetrexed 500 mg/m2 D1 IV Q3W Drug: Docetaxel 60 or 75 mg/m2 D1 IV Q3W Drug: Paclitaxel 175 or 200 mg/m2 D1 IV Q3W Drug: Gemcitabine 1000 mg/m2 or 1250 mg/m2 D1, 8 IV Q3W Drug: Placebo 20 ml D1 IV Q3W

Arm

Intervention/Treatment

Experimental: Sintilimab

Neoadjuvant Treatment period: up to 3 cycles of sintilimab plus platinum-based chemotherapy prior to surgery. adjuvant Treatment period: Subjects will receive sintilimab therapy after surgery until disease recurrence, unacceptable toxicity, receiving new anti-tumor therapy, withdrawal of informed consent (ICF), lost to follow-up or death, or other conditions that require treatment discontinuation (whichever occurs first). The maximum duration of postoperative treatment with either sintilimab or placebo is 1 year.

Drug: Sintilimab

200 mg D1 IV Q3W

Drug: Carboplatin

AUC 5 or 6 mg/ml/min D1 IV Q3W

Drug: Nab-paclitaxel

100 mg/m2 D1, 8, 15 IV Q3W

Drug: Cisplatin

75 mg/m2 D1 IV Q3W

Drug: Pemetrexed

500 mg/m2 D1 IV Q3W

Drug: Docetaxel

60 or 75 mg/m2 D1 IV Q3W

Drug: Paclitaxel

175 or 200 mg/m2 D1 IV Q3W

Drug: Gemcitabine

1000 mg/m2 or 1250 mg/m2 D1, 8 IV Q3W

Placebo Comparator: Placebo

Neoadjuvant Treatment period: up to 3 cycles of placebo plus platinum-based chemotherapy prior to surgery. adjuvant Treatment period: Subjects will receive placebo therapy after surgery until disease recurrence, unacceptable toxicity, receiving new anti-tumor therapy, withdrawal of informed consent (ICF), lost to follow-up or death, or other conditions that require treatment discontinuation (whichever occurs first). The maximum duration of postoperative treatment with either sintilimab or placebo is 1 year.

Drug: Carboplatin

AUC 5 or 6 mg/ml/min D1 IV Q3W

Drug: Nab-paclitaxel

100 mg/m2 D1, 8, 15 IV Q3W

Drug: Cisplatin

75 mg/m2 D1 IV Q3W

Drug: Pemetrexed

500 mg/m2 D1 IV Q3W

Drug: Docetaxel

60 or 75 mg/m2 D1 IV Q3W

Drug: Paclitaxel

175 or 200 mg/m2 D1 IV Q3W

Drug: Gemcitabine

1000 mg/m2 or 1250 mg/m2 D1, 8 IV Q3W

Drug: Placebo

20 ml D1 IV Q3W

Outcome Measures

Primary Outcome Measures

Event Free Survival (EFS) [Up to approximately 2 years following the beginning of Post-operative Assessment baseline(up to Study 5.4 years )]
EFS is defined as the time from randomization to the first recorded time to any first documented progression, recurrence or death, which occurs first.
Pathological Complete Response (pCR) Rate [Up to approximately 6 weeks following completion of neoadjuvant treatment (up to Study 2 years)]
pCR rate is defined as absence of residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy

Secondary Outcome Measures

Disease free survival (DFS) [Up to approximately 2 years following the begining of Post-operative Assessment baseline(up to Study 5.4 years )]
DFS is defined as the time from surgery to disease recurrence or death due to any cause.
Major Pathological Response (mPR) Rate [Up to approximately 6 weeks following completion of neoadjuvant treatment (up to Study 2 years)]
mPR rate is defined as ≤ 10% residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy.
Overall survival (OS) [Up to approximately 5.4 years]
OS is defined as the time from randomization to death due to any cause.
Safety parameters: AEs [Up to approximately 5.4 years]
The relationship of study drug and the severity of all adverse events (AEs)
Safety parameters:IRRs [Up to approximately 5.4 years]
The relationship of study drug and the severity of infusion-related reactions (IRRs).
Safety parameters: surgery delay rate [Up to approximately 5.4 years]
The relationship of study drug and the severity of surgery delay rate.
Immunogenicity-ADA [Up to approximately 1.6 years]
The positive rate of anti-drug antibody (ADA)
Immunogenicity-NAb [Up to approximately 1.6 years]
The positive rate of neutralizing antibody (NAb)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must sign the written informed consent form (ICF), and be able to follow the visits and relevant procedures specified in the protocol.
Age ≥ 18 years.
Cytologically or histologically confirmed primary NSCLC (including adenocarcinoma, squamous cell carcinoma).
Subjects with Stage IIB (primary tumor > 4 cm), IIIA or IIIB (resectable N2 only) disease based on the 8th edition of the TNM staging classification for lung cancer issued by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification (AJCC8).
Deemed radically resectable with curative intent.
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
Have not received any prior systemic anti-tumor therapy or local radiotherapy for NSCLC.

Exclusion Criteria:

Subjects with confirmed or suspected brain metastases.
Currently participating in an interventional clinical study or treatment with another study drug or study device within 4 weeks prior to randomization.
Received Chinese herbal medicine, Chinese traditional medicine with anti-tumor indications, or drugs with immunomodulatory effects (including thymosin, interferon, interleukin) within two weeks prior to randomization
Received a live attenuated vaccine 4 weeks prior to randomization (or planned to receive a live attenuated vaccine during the study).
Requiring long term systemic corticosteroids
Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive), known active syphilis.
Active hepatitis B. -