A Two-arm (Phase 2) Exploratory Study of Nivolumab Monotherapy or in Combination With Nab-paclitaxel and Carboplatin in Early Stage NSCLC in China

NCT ID: NCT04015778

Last Updated: 2020-02-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-08
• Study Completion Date: 2024-07-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 (240mg every 2 weeks), and adjuvant nivolumab (240mg IV, over 30 min, every 2 weeks) up to 12 months

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

240mg Q2W or 360mg Q3W

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 (240mg IV, over 30 min, every 2 weeks) up to 12 months

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: BIOLOGICAL

240mg Q2W or 360mg Q3W

carboplatin

Intervention Type: DRUG

AUC 5, d1 every three weeks

nab-paclitaxel

Intervention Type: DRUG

135 mg/m2, d1, 8

Interventions

Nivolumab

240mg Q2W or 360mg Q3W

Intervention Type: BIOLOGICAL

carboplatin

AUC 5, d1 every three weeks

Intervention Type: DRUG

nab-paclitaxel

135 mg/m2, d1, 8

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Guangdong Association of Clinical Trials

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yi-Long Wu

Role: CONTACT

syylwu@live.cn

+86 20 83827812 ext. 51221

Wen-zhao Zhong

Role: CONTACT

Facility Contacts

Wen-Zhao Zhong, MD

Role: primary

Yi-Long Wu, MD

Role: backup

syylwu@live.cn

+86 20 83827812 ext. 51221

References

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.

Reference Type: DERIVED

PMID: 38057314 (View on PubMed)

Other Identifiers

CTONG 1804

Identifier Type: -

Identifier Source: org_study_id