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

NCT04015778 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CTONG 1804
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• MPR (Major Pathological response) rate in 2 subgroups patients (PD-L1 <1%, and 1-49%) in Arm B

  The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks

• Proportion of resection without delay

  The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks

• Number of Participants with Adverse Events

  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

  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%)

  From date of enrollment up to the end of study, 5 years.

Other Outcomes (6)

• pCR rate

  The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks

• OS rate

  From date of enrollment up to the end of study, 5 years.

• ORR

  Within 4 to 6 weeks after the patient completes the neoadjuvant treatment

Study Arms (4)

Part 1: Nivolumab Mono

EXPERIMENTAL

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; Procedure: Radical resection for lung cancer

Part 1: Nivolumab Plus Chemo

EXPERIMENTAL

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

Biological: Nivolumab; Drug: carboplatin; Drug: nab-paclitaxel; Procedure: Radical resection for lung cancer

Part:2: Exploratory cohort

EXPERIMENTAL

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.

Biological: Nivolumab; Drug: carboplatin; Drug: nab-paclitaxel; Procedure: Radical resection for lung cancer

Part 3: Real-world cohort

EXPERIMENTAL

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.

Biological: Nivolumab; Drug: carboplatin; Drug: nab-paclitaxel; Procedure: Radical resection for lung cancer; Radiation: Radical radiation therapy; Drug: Chemotherapy (Cisplatin)

Interventions

Nivolumab BIOLOGICAL

Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks

Part 1: Nivolumab Mono; Part 1: Nivolumab Plus Chemo; Part 3: Real-world cohort; Part:2: Exploratory cohort

carboplatin DRUG

AUC 5, d1 every three weeks

Part 1: Nivolumab Plus Chemo; Part 3: Real-world cohort; Part:2: Exploratory cohort

nab-paclitaxel DRUG

135 mg/m2, d1, 8

Part 1: Nivolumab Plus Chemo; Part 3: Real-world cohort; Part:2: Exploratory cohort

Radical resection for lung cancer PROCEDURE

Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy. Segmentectomy and wedge resection are not permitted.

Part 1: Nivolumab Mono; Part 1: Nivolumab Plus Chemo; Part 3: Real-world cohort; Part:2: Exploratory cohort

Radical radiation therapy RADIATION

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).

Part 3: Real-world cohort

Chemotherapy (Cisplatin) DRUG

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

Part 3: Real-world cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Regardless of PD-L1 expression status.
• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Presence of at least one measurable lesion according to RECIST version 1.1.

You may not qualify if:

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

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences

Guangzhou, Guangdong, 510080, China

Location

Related Publications (1)

• 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.

  PMID: 38057314 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Carboplatin; 130-nm albumin-bound paclitaxel; Drug Therapy; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2019
• First Posted: July 11, 2019
• Study Start: August 8, 2019
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: May 20, 2026

Record last verified: 2026-04

Locations

CN (1)