Non Small Cell Lung Cancer
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGTislelizumab
Administered as an intravenous infusion once every 3 weeks
DRUGOciperlimab
Administered as an intravenous infusion once every 3 weeks
DRUGAlcestobart
Administered as an intravenous infusion once every 3 weeks
DRUGCisplatin
75 mg/m\^2 administered as an intravenous infusion once every 3 weeks
DRUGCarboplatin
Administered as an intravenous infusion once every 3 weeks at an area under the curve (AUC) of 5 mg/mL/min
DRUGPemetrexed
500 mg/m\^2 administered as an intravenous infusion once every 3 weeks in participants with non-squamous NSCLC
DRUGPaclitaxel
175 mg/m\^2 administered as an intravenous infusion once every 3 weeks in participants with squamous NSCLC
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 * Histologically confirmed Stage II-IIIA NSCLC (per the Eighth American Joint Committee on Cancer/Union Internationale Contre le Cancer \[NSCLC\] staging system) * Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent * Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained ≤ 7 days before randomization * Provide formalin-fixed paraffin-embedded block (preferred) or at least 15 freshly cut unstained FFPE slides of the primary tumor for biomarker evaluation during screening
Exclusion criteria
* Any prior antineoplastic therapy(ies) for current lung cancer (eg, radiotherapy, targeted therapies, ablation, or other systemic or local antineoplastic treatment) * Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-cell immunoglobulin and ITIM domain (TIGIT), anti-lymphocyte activation gene-3 (LAG-3), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways * Has mixed small cell lung cancer * Participants with large cell neuroendocrine carcinoma (LCNEC) * The presence of locally advanced unresectable NSCLC regardless of stage or metastatic disease * Known epidermal growth factor receptor (EGFR) sensitizing mutations and/or anaplastic lymphoma kinase (ALK) rearrangement NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) Rate | At the time of surgery, approximately Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) | At the time of surgery, approximately Week 16 | 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. |
| Event-free Survival (EFS) | From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2. | 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. |
| Event-free Survival Rate | 12 months and 24 months after randomization | 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. |
| Overall Survival (OS) | From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2. | 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. |
| Overall Survival Rate | 12 months and 24 months after randomization | 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. |
| Disease-free Survival (DFS) | From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2. | 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. |
| Disease-free Survival Rate | 12 months and 24 months after randomization | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | 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. |
| Feasibility of Surgery | At the time of surgery, approximately Week 16 | 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. |
| Duration of Surgery | Approximately Week 16 | The duration of surgery is defined as the time interval from the start of the surgical procedure to its completion. |
Countries
China
Contacts
STUDY_DIRECTORStudy Director
BeiGene
Participant flow
Recruitment details
This study enrolled 121 participants at study sites in China.
Pre-assignment details
In Substudy 1 participants with programmed death-ligand 1 (PD-L1) expression ≥ 50% were randomized to 1 of 3 treatment groups in a 1:1:1 ratio. In Substudy 2 participants with PD-L1 expression \< 50% were randomized into 1 of 2 treatment groups in a 1:2 ratio.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 8.03 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully Active) | 9 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Ambulatory with Restricted Activities) | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 121 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 19 Participants |
| Smoking Status Current | 5 Participants |
| Smoking Status Former | 79 Participants |
| Smoking Status Never | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 20 | 2 / 20 | 1 / 20 | 3 / 20 | 2 / 41 |
| other Total, other adverse events | 7 / 20 | 14 / 20 | 14 / 20 | 19 / 19 | 38 / 40 |
| serious Total, serious adverse events | 0 / 20 | 3 / 20 | 2 / 20 | 2 / 19 | 13 / 40 |
Outcome results
None listed