A Exploratory Study of Nivolumab Monotherapy or in Combination With Nab-paclitaxel and Carboplatin in Early Stage NSCLC in China

Nivolumab (BMS-936558) is a fully human, IgG4 (kappa) isotype mAb that binds PD-1 on activated immune cells and disrupts engagement of the receptor with its ligands PD-L1 (B7 H1/CD274) and PD-L2 (B7-DC/CD273), thereby abrogating inhibitory signals and augmenting the host antitumor response. In early clinical trials, nivolumab has demonstrated activity in several tumor types, including melanoma, renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC).

Nivolumab is in clinical development for the treatment of patients with NSCLC, RCC, melanoma, squamous cell carcinoma of the head and neck (SCCHN) and other tumors (eg, glioblastoma multiforme, mesothelioma, small cell lung cancer, gastric).

Nivolumab is approved in the United States (US), European Union, and other countries for the treatment of patients with unresectable or metastatic melanoma, advanced NSCLC with progression on or after platinum-based chemotherapy, advanced RCC whose disease progressed on an antiangiogenic therapy, classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin treatment, and recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy.

The proposed study will evaluate the efficacy and safety of preoperative administration of Nivolumab or Nivolumab combined with nab-paclitaxel and carboplatin in neoadjuvant setting and administration of Nivolumab in adjuvant setting in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune microenvironment and circulating immune cells in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: nab-paclitaxel; Biological: Nivolumab; Procedure: Radical resection for lung cancer; Biological: Nivolumab; Radiation: Radical radiation therapy; Drug: Chemotherapy (Cisplatin)

• Study Type: Interventional
• Enrollment (Estimated): 316
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically confirmed Stage II or IIIA non-small cell lung cancer (NSCLC) (per TNM 8th edition; AJCC 8th edition), including T3N2M0 tumors, deemed to be completely resectable.
2. Regardless of PD-L1 expression status.
3. EGFR and ALK wild-type. If testing is performed, it should be conducted locally using assays approved by the National Medical Products Administration (NMPA/formerly CFDA).
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Presence of at least one measurable lesion according to RECIST version 1.1.

Exclusion Criteria:

1. Presence of locally advanced, inoperable or metastatic disease
2. Participants with active, known or suspected autoimmune disease
3. Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)
4. EGFR mutation or ALK transsituation (+)

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Nivolumab Mono; In arm A, 24 participants will be enrolled into this arm according to PD-L1 expressing level (≥50%).Arm A consists of 3 cycles of neoadjuvant nivolumab (360mg every 3 weeks), and adjuvant nivolumab (360mg IV, every 3 weeks) up to 12 months	Biological: Nivolumab; Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks; Procedure: Radical resection for lung cancer; Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy. Segmentectomy and wedge resection are not permitted.; Biological: Nivolumab; Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.
Experimental: Part 1: Nivolumab Plus Chemo; In arm B, up to 12 participants will be enrolled into each subgroup according to PD-L1 expressing level (<1% and 1%-49%).arm B consists of 3 cycles of neoadjuvant nivolumab (360mg every 3 weeks) with nab-paclitaxel and carboplatin(nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every three weeks ), and adjuvant nivolumab (360mg IV, every 3 weeks) up to 12 months	Drug: carboplatin; AUC 5, d1 every three weeks; Drug: nab-paclitaxel; 135 mg/m2, d1, 8; Biological: Nivolumab; Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks; Procedure: Radical resection for lung cancer; Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy. Segmentectomy and wedge resection are not permitted.; Biological: Nivolumab; Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.
Experimental: Part:2: Exploratory cohort; In part 2，the treatment regimen consists of three cycles of neoadjuvant nivolumab (360 mg every 3 weeks) in combination with nab-paclitaxel and carboplatin (nab-paclitaxel 135 mg/m² on days 1 and 8, and carboplatin AUC 5 on day 1, every 3 weeks), followed by adjuvant nivolumab (360 mg every 3 weeks, administered via IV infusion over at least 30 minutes) for up to 12 months. A total of 53 subjects will be enrolled in this study, regardless of PD-L1 expression.	Drug: carboplatin; AUC 5, d1 every three weeks; Drug: nab-paclitaxel; 135 mg/m2, d1, 8; Biological: Nivolumab; Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks; Procedure: Radical resection for lung cancer; Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy. Segmentectomy and wedge resection are not permitted.; Biological: Nivolumab; Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.
Experimental: Part 3: Real-world cohort; Part 3 aims to evaluate the real-world effectiveness of neoadjuvant chemoimmunotherapy in patients with EGFR/ALK wild-type, potentially resectable or unresectable Stage III NSCLC. Treatment Paradigm: Eligible subjects will receive 3 cycles of neoadjuvant chemoimmunotherapy. Subsequently, a Multidisciplinary Team (MDT) will evaluate and determine the optimal definitive local therapy, triage patients to either radical resection or concurrent chemoradiotherapy (CCRT). Following the completion of local therapy, patients will receive adjuvant or consolidation immunotherapy for a duration of 1 year, administered every 3 weeks (Q3W). Sample Size: The planned enrollment for Part 3 is 215 patients.	Drug: carboplatin; AUC 5, d1 every three weeks; Drug: nab-paclitaxel; 135 mg/m2, d1, 8; Biological: Nivolumab; Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks; Procedure: Radical resection for lung cancer; Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy. Segmentectomy and wedge resection are not permitted.; Biological: Nivolumab; Within 6 weeks after definitive surgery, subjects in each cohort who are assessed to have benefited from neoadjuvant therapy (CR, PR, or SD) and have adequately recovered from surgery may receive adjuvant nivolumab (360 mg via IV infusion over at least 30 minutes, every 3 weeks) for up to 12 months, or until disease recurrence or unacceptable toxicity.; Radiation: Radical radiation therapy; In Part 3, for patients who are assessed by a Multidisciplinary Team (MDT) as unable to achieve R0 resection following neoadjuvant chemo-immunotherapy induction, the recommended radiotherapy regimen is: 60 Gy in 30 fractions (5 fractions per week) to 95% of the planning target volume (PTV).; Drug: Chemotherapy (Cisplatin); Part 3: For patients who are determined by a Multidisciplinary Team (MDT) to be ineligible for R0 resection following neoadjuvant chemo-immunotherapy induction and require definitive radiotherapy, concurrent chemotherapy will be administered. The regimen consists of cisplatin 30 mg/m² administered once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR (Major Pathological Response) rate	As the primary outcome in part 1. MPR rate, defined as the number of participants with <10% residual tumor in lung and lymph nodes, divided by the number of treated participants for each arm. Viable tumors in situ carcinoma should not be included in the MPR calculation.	The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
EFS	Primary Outcome for Part 2. Outcome Measure Definition: Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: Disease progression that precludes surgical treatment; Local or distant recurrence; Death from any cause. Progression and recurrence will be assessed by the investigator according to RECIST 1.1. Subjects who die without documented disease progression or recurrence will be considered to have experienced an EFS event on the date of death.	Since the last patient was enrolled for follow-up for 36 months
18 months EFS rate	Primary Outcome for Part 3. Outcome Measure Definition: 18months Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: Disease progression that precludes surgical treatment; Local or distant recurrence; Death from any cause. Progression and recurrence will be assessed by the investigator according to RECIST 1.1. Subjects who die without documented disease progression or recurrence will be considered to have experienced an EFS event on the date of death.	The patient was followed up for 18 months after frist cycle neoajuvant treatment.
Surgical Conversion Rate	The primary endpoint of Part 3 is the surgical conversion rate, defined as the proportion of patients who successfully undergo definitive surgery following neoadjuvant chemoimmunotherapy, relative to the total enrolled population (Intent-to-Treat [ITT] analysis set). Statistical Analysis: The surgical conversion rate will be summarized descriptively using frequencies and percentages. The two-sided 95% exact confidence interval (CI) for the proportion will be calculated using the Clopper-Pearson method.	Perioperative/Periprocedural

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR (Major Pathological response) rate in 2 subgroups patients (PD-L1 <1%, and 1-49%) in Arm B	In part 1	The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
Proportion of resection without delay	In part 1and 2	The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
Number of Participants with Adverse Events	In parts 1 and 2 Safety and tolerability will be measured by incidence of AE, SAE, immune related AEs, deaths, and laboratory abnormalities	During the treatment period, within at least 100 days after the cessation of neoadjuvant therapy, within 90 days after surgery, and within 30 days after adjuvant therapy.
MRP rate	Also, as the primary outcome in part 1. MPR rate, defined as number participants with <10% residual tumor in lung and lymph nodes, divided by the number of treated participants for each arm Viable tumors in situ carcinoma should not be included in MPR calculation.	The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
The EFS rates of all subjects with different PD-L1 expression statuses (PD-L1 < 1%, 1-49% and ≥ 50%)	In parts 1 and 2. Outcome Measure Definition: Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: Disease progression that precludes surgical treatment; Local or distant recurrence; Death from any cause. Progression and recurrence will be assessed by the investigator according to RECIST 1.1. Subjects who die without documented disease progression or recurrence will be considered to have experienced an EFS event on the date of death.	From date of enrollment up to the end of study, 5 years.
12 months EFS rate	In part 3, the 12-month EFS rate is the proportion of subjects who are alive and event-free at 12 months after the start of treatment.	After 12 months of enrollment for all patientsAfter 12 months of enrollment for all patients
OS	In part 3, OS is defined as the time from the start of treatment to death for any reason	From the date of enrollment until the date of death, assessed up to 100 months
TDDM (Time to Death or Distant Metastasis)	In part 3, TDDM is defined as the start of the first treatment to distant metastasis, or death from any cause, whichever occurs first	From the date of the first dose of study treatment until the date of first documented distant metastasis or death from any cause, whichever occurs first, assessed up to approximately 60 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	The pCR (complete pathological response) rate is defined as the number of subjects with no residual tumor cells in the lungs and lymph nodes divided by the number of subjects receiving treatment.	The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
OS rate	OS is defined as the time since the treatment date and the death date, with the deletion date being the last known date when the subject was still alive	From date of enrollment up to the end of study, 5 years.
ORR	ORR is defined as the optimal objective tumor response rate between neoadjuvant therapy and surgery (according to RECIST 1.1 criteria). All subjects will have their ORR calculated.	Within 4 to 6 weeks after the patient completes the neoadjuvant treatment
Safty	Descriptive statistical analysis of safety data was conducted based on the 4th edition of NCI CTCAE. According to the most severe level determined by NCI CTCAE V4, all AE/ SAEs that occur after treatment and treatment-related AE/ SAEs will be summarized by systemic organ classification and standard terms.	From the time of enrollment until the completion of adjuvant therapy, which lasted for 13 weeks
18m-DFS rate	Disease-Free Survival (DFS) is defined as the time from the date of surgery to any of the following events: disease progression, recurrence, or death from any cause. Disease progression and recurrence will be assessed according to RECIST 1.1 criteria. For subjects who do not experience a DFS event, the date of censoring will be the date of the last evaluable tumor assessment after surgery. For subjects who do not experience a DFS event but start subsequent anti-cancer therapy, the date of censoring will be the date of the last evaluable tumor assessment prior to receiving the subsequent anti-cancer therapy.	The 18-month DFS rate refers to the probability of being event-free at 18 months calculated from the date of surgery.
Landmark MRD positive rate	In part 3, the Landmark MRD positive rate is defined as the proportion of patients who were MRD positive at the Landmark time point among the total study population. Furthermore, the comparison is made between the proportion of patients with MRD positivity among those who underwent surgery and the proportion of patients with MRD positivity among those who received radiotherapy.	One month after local therapy

Collaborators and Investigators

• Sponsor: Guangdong Association of Clinical Trials
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Liu SY, Dong S, Yang XN, Liao RQ, Jiang BY, Wang Q, Ben XS, Qiao GB, Lin JT, Yan HH, Yan LX, Nie Q, Tu HY, Wang BC, Yang JJ, Zhou Q, Li HR, Liu K, Wu W, Liu SM, Zhong WZ, Wu YL. Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC (CTONG1804): a multicenter open-label phase II study. Signal Transduct Target Ther. 2023 Dec 6;8(1):442. doi: 10.1038/s41392-023-01700-4.

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2019
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: April 1, 2026

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; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Platinum Compounds; Nivolumab; Carboplatin; Cisplatin; Drug Therapy; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: CTONG 1804

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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