This study was conducted to evaluate the preliminary effectiveness and safety of treatment with tislelizumab alone and in combination with other investigational agents prior to surgery (neoadjuvant treatment) in adults with non-small cell lung cancer (NSCLC) that is able to be removed by surgery.
This is a randomized, open-label, multicenter, Phase 2, umbrella study to evaluate the preliminary efficacy, safety, and pharmacodynamics of tislelizumab as monotherapy and in combination with investigational agents as neoadjuvant treatment in Chinese participants with resectable Stage II to IIIA NSCLC. The study is designed with the flexibility of adding treatment arms as new treatments become available or discontinuing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and of modifying the participant population. The study consisted of a neoadjuvant treatment phase (2 - 4 cycles of treatment), a surgery phase and a follow-up phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
121
Administered as an intravenous infusion once every 3 weeks
Administered as an intravenous infusion once every 3 weeks
Administered as an intravenous infusion once every 3 weeks
The First Affiliated Hospital of Wannan Medical College
Wuhu, Anhui, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Major Pathological Response (MPR) Rate
Tumor tissue and lymph node tissue obtained from surgical resection were sent to a central laboratory according to study pathology manuals for pathological response analysis. MPR rate is defined as the percentage of participants with ≤ 10% residual viable tumor in the resected primary tumor and all resected lymph nodes as assessed by blinded independent pathology review (BIPR). Participants without surgery or pathological results were considered non-responders.
Time frame: At the time of surgery, approximately Week 16
Pathological Complete Response (pCR)
Pathological complete response is defined as the percentage of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes as assessed by the BIPR. Participants without surgery or pathological results were considered as non-responders.
Time frame: At the time of surgery, approximately Week 16
Event-free Survival (EFS)
EFS is defined as the time from randomization until any of the following events, whichever occurred first: radiographic disease progression that precludes definitive surgery, local or distant recurrence as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause. Local recurrence is defined as recurrence in the ipsilateral thorax (lymph node or lung on the same side as Baseline location) including lung parenchyma, bronchial stump, main trachea, hilum or mediastinal lymph nodes (including subcarinal lymph nodes), pleura and chest wall diagnosed by radiological examination and/or histopathological confirmation. Distant recurrence (metastasis) is defined as spread of disease beyond the area of the ipsilateral thorax (including contralateral area and other organs) diagnosed by radiological examination and/or histopathological confirmation. Median EFS was estimated using Kaplan-Meier methodology.
Time frame: From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
75 mg/m\^2 administered as an intravenous infusion once every 3 weeks
Administered as an intravenous infusion once every 3 weeks at an area under the curve (AUC) of 5 mg/mL/min
500 mg/m\^2 administered as an intravenous infusion once every 3 weeks in participants with non-squamous NSCLC
175 mg/m\^2 administered as an intravenous infusion once every 3 weeks in participants with squamous NSCLC
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
The First Affiliated Hospital of Guangzhou Medical Universitydatansha Hospital)
Guangzhou, Guangdong, China
The Tumor Hospital Affiliated to Guangxi Medical University
Nanning, Guangxi, China
Anyang Cancer Hospital
Anyang, Henan, China
Hubei Cancer Hospital
Wuhan, Hubei, China
Hunan Cancer Hospital
Changsha, Hunan, China
The First Affiliated Hospital of Nanchang University Branch Xianghu
Nanchang, Jiangxi, China
Liaoning Cancer Hospital and Institute
Shenyang, Liaoning, China
...and 4 more locations
Event-free Survival Rate
Event-free survival rate is defined as the percentage of participants with none of the following events: radiographic disease progression that precludes definitive surgery, local or distant recurrence as assessed by investigator per RECIST v1.1, or death due to any cause. Local recurrence is defined as recurrence in the ipsilateral thorax (lymph node or lung on the same side as Baseline location) including lung parenchyma, bronchial stump, main trachea, hilum or mediastinal lymph nodes (including subcarinal lymph nodes), pleura and chest wall diagnosed by radiological examination and/or histopathological confirmation. Distant recurrence (metastasis) is defined as spread of disease beyond the area of the ipsilateral thorax (including contralateral area and other organs) diagnosed by radiological examination and/or histopathological confirmation. EFS rates were estimated using the Kaplan-Meier method with the corresponding 95% confidence interval constructed using Greenwood's formula.
Time frame: 12 months and 24 months after randomization
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology.
Time frame: From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.
Overall Survival Rate
Overall survival rate is defined as the percentage of participants who were still alive at the analysis time points. OS rates were estimated using the Kaplan-Meier method with the corresponding 95% confidence interval constructed using Greenwood's formula.
Time frame: 12 months and 24 months after randomization
Disease-free Survival (DFS)
DFS is defined as the time from the first date of no disease (ie, participants who underwent margin-negative \[R0\] resection) to local or distant recurrence, as assessed by the investigator according to RECIST v1.1, or death due to any cause, whichever occurred first. Median DFS was estimated using Kaplan-Meier methodology.
Time frame: From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.
Disease-free Survival Rate
Disease-free survival rate is defined as the percentage of participants with none of the following events: Local or distant recurrence as assessed by the investigator per RECIST v1.1, or death due to any cause. Local recurrence is defined as recurrence in the ipsilateral thorax (lymph node or lung on the same side as Baseline location) including lung parenchyma, bronchial stump, main trachea, hilum or mediastinal lymph nodes (including subcarinal lymph nodes), pleura and chest wall diagnosed by radiological examination and/or histopathological confirmation. Distant recurrence (metastasis) is defined as spread of disease beyond the area of the ipsilateral thorax (including contralateral area and other organs) diagnosed by radiological examination and/or histopathological confirmation. DFS rates were estimated using the Kaplan-Meier method with the corresponding 95% confidence interval constructed using Greenwood's formula.
Time frame: 12 months and 24 months after randomization
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: * Resulted in death * Was life-threatening * Required hospitalization or prolongation of existing hospitalization * Resulted in disability/incapacity * Was a congenital anomaly/birth defect * Was considered a significant medical AE by the investigator or sponsor based on medical judgement (eg, may have jeopardized the participant or may require medical/surgical intervention to prevent one of the outcomes listed above). Immune-mediated adverse events (imAEs) are autoimmune-mediated complications that may develop in response to immunotherapeutic agents. Immune-mediated AEs were collected from the date of first dose of study drug to 90 days after the last dose of study drug, regardless of whether the participant started a new anticancer therapy or prespecified adjuvant treatment. imAEs were identified by the investigator based on a standard process defined in the Protocol.
Time frame: From first dose of study drug until 30 days after last dose or new anticancer treatment, whichever occurred first, or up to 90 days after the last dose for imAEs; maximum duration of treatment was 14 weeks.
Feasibility of Surgery
Feasibility of surgery was assessed by the number of participants who underwent surgical resection (surgery) within 6 weeks of last dose of study drug, had delayed or canceled surgery, the approach of surgery, duration of surgery (see next outcome measure) ,and the number of participants who underwent an exploratory thoracotomy, a surgical procedure in which a cut is made between the ribs to see and reach the lungs or other organs in the chest or thorax. Exploratory thoracotomy was not counted as surgery.
Time frame: At the time of surgery, approximately Week 16
Duration of Surgery
The duration of surgery is defined as the time interval from the start of the surgical procedure to its completion.
Time frame: Approximately Week 16