Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Mitogens

Gefitinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

SH-1028 tablets (200 mg orally, once daily) plus placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule.

Interventions:

Drug: SH-1028 tablets 200 mg Drug: Placebo Gefitinib 250 mg

Gefitinib (250 mg orally, once daily) plus placebo SH-1028 tablets (200mg orally, once daily), in accordance with the randomisation schedule.

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).

Interventions:

Drug: Gefitinib 250 mg Drug: Placebo SH-1028 tablets 200mg

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.

SH-1028 tablets

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.

Placebo SH-1028 tablets

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).

The initial dose of Gefitinib is 250 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment.

Placebo Gefitinib

Han Luwei

Zhou Caicun, Professor

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.

Participants are randomly assigned to SH-1028 tablets arm or Gefitinib arm based on the mutation condition of EGFR (L858R or 19Del) and brain metastases (yes or no). The rate of SH-1028 tablets arm to Gefitinib arm is 2:1.

All trial personnel and participants were masked to treatment allocation, until unblinding due to progression disease or other Criteria of termination.

A Study of SH-1028 Tablets Versus Gefitinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

A Phase III, Double-blind, Randomised Study of SH-1028 Tablets Versus Gefiitinib as First Line Treatment in Patients With Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non Small Cell Lung Cancer

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.

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.

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).

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).

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).

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).

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.

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.

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.

Incidence rate of serious adverse events (SAEs) was one of main outcome measures to compare the safety of SH-1028 Tablets and Gefitinib.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of SH-1028 Tablets Versus Gefitinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer	NCT04239833	Non-Small Cell ...	SH-1028 tablets Placebo SH-1028... Gefitinib Placebo Gefitin...	18 Years -	Nanjing Sanhome Pharmaceutical, Co., Ltd.
A Study of SH-1028 Tablets Versus Gefitinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer	NCT04239833	Non-Small Cell ...	SH-1028 tablets Placebo SH-1028... Gefitinib Placebo Gefitin...	18 Years -	Nanjing Sanhome Pharmaceutical, Co., Ltd.

Spots Global Cancer Trial Database for placebo gefitinib