Non Small Cell Lung Cancer
Conditions
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.
Interventions
BIOLOGICALNivolumab
Nivolumab 360 mg IV (administered intravenously for more than 30 minutes) every 3 weeks
DRUGcarboplatin
AUC 5, d1 every three weeks
DRUGnab-paclitaxel
135 mg/m2, d1, 8
PROCEDURERadical resection for lung cancer
Including lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy. Segmentectomy and wedge resection are not permitted.
RADIATIONRadical 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).
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
Sponsors
Guangdong Association of Clinical Trials
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MPR (Major Pathological Response) rate | The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks | 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. |
| EFS | Since the last patient was enrolled for follow-up for 36 months | 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. |
| 18 months EFS rate | The patient was followed up for 18 months after frist cycle neoajuvant treatment. | 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. |
| Surgical Conversion Rate | Perioperative/Periprocedural | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | In part 1 |
| Proportion of resection without delay | The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks | In part 1and 2 |
| 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. | In parts 1 and 2 Safety and tolerability will be measured by incidence of AE, SAE, immune related AEs, deaths, and laboratory abnormalities |
| MRP rate | The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks | 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 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. | 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. |
| 12 months EFS rate | After 12 months of enrollment for all patientsAfter 12 months of enrollment for all patients | 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. |
| OS | From the date of enrollment until the date of death, assessed up to 100 months | In part 3, OS is defined as the time from the start of treatment to death for any reason |
| TDDM (Time to Death or Distant Metastasis) | 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. | In part 3, TDDM is defined as the start of the first treatment to distant metastasis, or death from any cause, whichever occurs first |
Countries
China
Outcome results
None listed