To assess the efficacy and safety of SH-1028 tablets versus Gefitinib, a standard of care epidermal growth factor receptor tyrosine kinase inhibitor, in patients with locally advanced or Metastatic Non Small Cell Lung Cancer
This is a Phase III, multi-center,double-blind, randomised study assessing the efficacy and safety of SH-1028 tablets (200 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) ( gefitinib, 250 mg orally, once daily) in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naive and eligible for first-line treatment with an EGFR-TKI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
240
The initial dose of SH-1028 tablets is 200 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
The initial dose of Placebo SH-1028 tablets is 200 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
The initial dose of Gefitinib is 250 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label SH-1028 tablets (crossover to active SH-1028 tablets).
Median Progression Free Survival (PFS)
Progression-free survival was defined as the time from randomization until the date of objective disease progression regardless of whether the participant withdrew from randomized therapy and was used to assess the efficacy of SH-1028 tablets compared with Gefitinib (SoC EGFR-TKI therapy) as measured by PFS. The primary endpoint of PFS was based on Investigator assessment.
Time frame: At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.
Objective Response Rate (ORR)
ORR was defined as the number (%) of participants with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of SH-1028 tablets compared with Gefitinib (SoC EGFR-TKI therapy). ORR was based on Investigator assessment.
Time frame: At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.
Duration of Response (DoR)
Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of SH-1028 tablets compared with Gefitinib (SoC EGFR-TKI therapy).
Time frame: At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.
Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of SH-1028 tablets compared with Gefitinib (SoC EGFR-TKI therapy).
Time frame: At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.
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The initial dose of Gefitinib is 250 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment.
Depth of Response（DepOR）
The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of SH-1028 tablets compared with Gefitinib (SoC EGFR-TKI therapy).
Time frame: At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.
Overall Survival (OS)
Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of SH-1028 tablets compared with Gefitinib (SoC EGFR-TKI therapy).
Time frame: From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 30 months)
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13)
The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit, including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Time frame: At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30)
The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, combined to produce 5 functional scales, 3 symptom scales, 6 individual items, and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit, including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Time frame: At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.
Number of adverse events (AEs)
Number of adverse events (AEs) assessed by CTCAE 5.0 was one of main outcome measures to compare the safety of SH-1028 Tablets and Gefitinib.
Time frame: From first dose to 28 days after SH-1028 tablets discontinuation.
Incidence rate of serious adverse events (SAEs)
Incidence rate of serious adverse events (SAEs) was one of main outcome measures to compare the safety of SH-1028 Tablets and Gefitinib.
Time frame: From first dose to 28 days after SH-1028 tablets discontinuation.