Clinical trial NCT04015778: A Two-arm (Phase 2) Exploratory Study of Nivolumab Monotherapy or in Combination With Nab-paclitaxel and Carboplatin in Early Stage NSCLC in China
Official title: A Two-arm (Phase 2) Exploratory Study of Nivolumab Monotherapy or in Combination With Nab-paclitaxel and Carboplatin in Early Stage NSCLC in China
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Lead sponsor: Guangdong Association of Clinical Trials
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2019-07-11
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Early stage IB-IIIA, operable non-small cell lung cancer, confirmed in tissue
* Lung function capacity capable of tolerating the proposed lung surgery
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
* Available tissue of primary lung tumor

Exclusion Criteria:

* 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)

Other protocol defined inclusion/exclusion criteria could apply

Primary outcomes:
measure: MPR rate
timeFrame: The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
Secondary outcomes:
measure: MPR rate in 2 subgroups patients (PD-L1 <1%, and 1-49%) in Arm B
timeFrame: The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
measure: Proportion of resection without delay
timeFrame: The patients considered to be technically resectable will undergo resection，an expected average of 13 weeks
measure: Number of Participants with Adverse Events
timeFrame: During the neoadjuvant period and 100 days post adjuvant period
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences
state: Guangdong
Study officials:
References: