Neoadjuvant and Adjuvant Therapy Studies of Sindilizumab in Resectable Lung Cancer

A Randomized, Double-blind, Phase 3 Study of the Efficacy and Safety of Sindilizumab Combined With Chemotherapy or Placebo Combined With Chemotherapy for Neoadjuvant and Adjuvant Therapy for Resectable Non-small Cell Lung Cancer (ORIENT-99)

This study is a randomized, double-blind Phase 3 study to compare the efficacy and safety of Sindilizumab combined with chemotherapy or placebo combined with chemotherapy for neoadjuvant and adjuvant therapy for Resectable Stage II to IIIB (resectable N2 only) non-small cell lung cancer (NSCLC).

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Sintilimab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Placebo; Drug: Nab paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 506
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects must sign the written informed consent form (ICF), and be able to follow the visits and relevant procedures specified in the protocol.
2. Age ≥ 18 years.
3. Cytologically or histologically confirmed primary NSCLC (including adenocarcinoma, squamous cell carcinoma).
4. Subjects with Stage II, 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).
5. Deemed radically resectable with curative intent.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
7. Have not received any prior systemic anti-tumor therapy or local radiotherapy for NSCLC.

Exclusion Criteria:

1. Subjects with confirmed or suspected brain metastases.
2. Currently participating in an interventional clinical study or treatment with another study drug or study device within 4 weeks prior to randomization.
3. 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
4. Received a live attenuated vaccine 4 weeks prior to randomization (or planned to receive a live attenuated vaccine during the study).
5. Requiring long term systemic corticosteroids
6. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive), known active syphilis.
7. Active hepatitis B.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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 1 cycle of sintilimab plus platinum-based chemotherapy, and then 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 13 cycles.	Drug: Sintilimab; 200 mg D1 IV Q3W; Drug: Carboplatin; AUC 5 or 6 mg/ml/min D1 IV Q3W; Drug: Cisplatin; 75 mg/m2 D1 IV Q3W; Drug: Pemetrexed; 500 mg/m2 D1 IV Q3W; Drug: Paclitaxel; 175 or 200 mg/m2 D1 IV Q3W; Drug: Nab paclitaxel; 100 mg/m2 D1, 8, 15 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 1 cycle of placebo plus platinum-based chemotherapy, and then 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 13 cycles.	Drug: Carboplatin; AUC 5 or 6 mg/ml/min D1 IV Q3W; Drug: Cisplatin; 75 mg/m2 D1 IV Q3W; Drug: Pemetrexed; 500 mg/m2 D1 IV Q3W; Drug: Paclitaxel; 175 or 200 mg/m2 D1 IV Q3W; Drug: Placebo; 20 ml D1 IV Q3W; Drug: Nab paclitaxel; 100 mg/m2 D1, 8, 15 IV Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival (EFS) in stage III NSCLC	Up to approximately 2 years following the beginning of Post-operative Assessment baseline(up to Study 2 years )	Up to approximately 2 years following the beginning of Post-operative Assessment baseline(up to Study 2 years )
Event Free Survival (EFS) in ITT population	EFS is defined as the time from randomization to the first recorded time to any first documented progression, recurrence or death, which occurs first.	Up to approximately 3 years following the beginning of Post-operative Assessment baseline(up to Study 3 years )

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival (DFS)	DFS is defined as the time from surgery to disease recurrence or death due to any cause.	Up to approximately 2 years following the begining of Post-operative Assessment baseline(up to Study 5.4 years )
Overall survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 5.4 years
Major Pathological Response (mPR) Rat	mPR rate is defined as ≤ 10% residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy.	Up to approximately 6 weeks following completion of neoadjuvant treatment (up to Study 2 years)
Safety parameters:AE	The relationship of study drug and the severity of all adverse events (AEs), treatment emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), immune-related adverse events (irAEs), serious adverse events (SAEs), infusion-related reactions (IRRs) and surgery delay rate.	Up to approximately 5.4 years

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): October 14, 2028

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 22, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Pemetrexed; Carboplatin; Paclitaxel
• Other Study ID Numbers: CIBI308G301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No