non-small cell lung cancer
Conditions
Interventions
Trade Name: Pyrotinib
Product Name: Pyrotinib Maleate
Product Code: [SHR1258]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Pyrotinib Maleate
CAS Number: 1397922-61-0
Current Sponsor co
Sponsors
Jiangsu Hengrui Medicine Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent which is approved by IRB/EC, willing and able to comply with scheduled treatment, all examinations at study visits, and other study procedures. 2. Male or female, >=18 years old. 3. ECOG PS 0-1 (see APPENDIX 2 for ECOG PS criteria). 4. Have histologically or cytologically confirmed locally advanced (must have been evaluated by the investigator that are not amenable to curable surgery or radiotherapy) or metastatic non-squamous NSCLC disease (Stage IIIB – IV, according to the International Association for the Study of Lung Cancer (IASLC) cancer staging system, 8th edition [APPENDIX 3]). 5. Before enrollment, a documented confirmed presence of activating mutations in exon 20 of the HER2 gene must be provided. Sufficient tumor tissue samples should be provided to retrospectively confirm the mutation status of the HER2 gene. For examples of HER2 (ERBB2) exon 20 mutations see APPENDIX 4. The tumor tissue samples should be: neutral buffered formalin fixed, paraffin-embedded [FFPE] blocks or at least 6-12 unstained (6-10 surgical biopsies, or at least 12 core needle biopsies) tumor tissue slices, fresh or archived (fresh samples are preferred). For patients who cannot provide the required biopsies, their enrollment can be discussed with the sponsor. 6. Must have measureable disease per RECIST v1.1. The definition of CT or MRI measurable lesion as the target lesion: according to RECIST v1.1, the long diameter of such lesion should be >=10 mm by the spiral CT scan or the short diameter of enlarged lymph nodes >=15 mm; lesions that have previously received local treatment can be used as target lesions after the confirmation of progress according to the RECIST v1.1 standard. 7. For advanced NSCLC, patients must have had progressive disease on or after a platinum based chemotherapy, with or without immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) and/or anti-angiogenic drugs. No more than 2 prior lines of systemic therapy are allowed. Two scenarios of neoadjuvant/adjuvant therapy are allowed: a) subjects who received adjuvant or neoadjuvant platinum based chemotherapy and developed recurrent or metastatic disease within 6 months of completing therapy are eligible; b) subjects with recurrent disease > 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum based regimen given to treat the recurrence, are eligible. 8. The laboratory test values must meet the following standards to manifest that the functional level of important organs/systems meets the requirements: • Hematology (not corrected by blood/blood products transfusion, or transfusion of hematopoietic stimulating factors such as G-CSF/TPO, etc. within 14 days before the test): ANC >=1.5 × 109/L; PLT >=100 × 109/L; Hb >=80 g/L; • Blood biochemistry (liver function): TBIL =50 mL/min (Cockcroft-Gault formula); 9. Female of childbearing potential must have a serum pregnancy test within 7 days before the first dose and the result is negative. Female patient of childbearing potential (WOCBP) and male patient whose partner is WOCBP must agree to use effective contraception method during the study period and within 8 weeks after the last dose (if receiving docetaxel treatment only, after the last dose, 3 months for male patient whose p
Exclusion criteria
Exclusion criteria: 1. Target disease exclusion criteria 1) Malignant tumors with other pathological types, such as mixed cancer, double primary cancers; 2) Medical history of other active malignancies within last 5 years; Exceptions: skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, prostate cancer in situ, or cervical carcinoma in situ, for which by the date of the first dose of study drug, at least 2 years of complete remission and no other treatment is needed or expected during the study period. 3) Subjects with active CNS metastases are excluded. Subjects with history or evidence of current leptomeningeal metastases are excluded. Subjects are eligible if CNS metastases are adequately treated (surgery or radiotherapy) and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of = weeks (or 5 half-lives of the drug, to whichever is shorter); • anti-tumor traditional Chinese medicine treatment >=2 weeks; • major surgery (requires hospitalization) >=2 weeks; • minimally invasive surgery (puncture, biopsy, endoscope, etc.) >=1 week; • with > 30 Gy non-thoracic radiotherapy >=4 weeks; • with > 30 Gy thoracic radiotherapy >=24 weeks; • with =2 weeks. Furthermore, it is required that the adverse event has resolved from the previous drug treatment/medical interventions (except for alopecia or fatigue within NCI-CTCAE v5.0 Grade 1) 2. Medical history exclusion criteria 1) Patients with active (not medically treated) CNS diseases, such as benign brain tumors, benign meningiomas, other leptomeningeal diseases, and poorly controlled (occurs within 6 months prior to the first dose of study treatment) cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc). Patients are eligible if the above-mentioned disease has been adequately treated and clinically stable prior to the first dose of study treatment (by radiological assessments [preferred enhanced MRI or CT] and maintained for at least 2 weeks, and the relevant symptoms have been resolved to NCI-CTCAE v5.0 Grade =2 myocardial ischemia; (4) Grade >=2 cardiac insufficiency according to New York Heart Association (NYHA) Fun
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) of pyrotinib versus docetaxel in patients with advanced non-squamous non-small cell lung cancer (NSCLC) harboring a HER2 exon 20 mutation who progressed after treatment with platinum based chemotherapy. The PFS endpoint will be determined by blinded independent radiology review committee (BIRC).;Secondary Objective: - To compare the efficacy of pyrotinib versus docetaxel in patients with advanced HER2 exon20-mutated non-squamous NSCLC who have progressed after treated with platinum based chemotherapy, through evaluations of overall survival (OS), and objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and time to tumor progression (TTP) assessed by BIRC, and ORR, DCR, DoR, TTP, PFS and PFS2 assessed by investigator; -To evaluate the safety of pyrotinib versus docetaxel in patients with advanced HER2 exon20-mutated non-squamous NSCLC who have progressed after treated with platinum based chemotherapy; -To evaluate patient reported outcomes (PRO) in pyrotinib versus docetaxel treatment arms; -To evaluate pharmacokinetics (PK) of pyrotinib in patients with advanced HER2 exon20-mutated non-squamous NSCLC who have progressed after treated with platinum based chemotherapy;;Primary end point(s): PFS evaluated by the blinded independent review committee (BIRC) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).;Timepoint(s) of evaluation of this end point: PFS will be collected on Day 1 of each dosing cycle, at discontinuation of treatment/withdrawal, at safety follow-up: 28 days (±7) after the last dose and at Survival follow-up (comes after safety followup). Every 56 days (±7 days) after the last dose investigators must follow up subject’s survival via phone calls. The definition of the Follow-up period is: in addition to safety follow-up and survival follow-up, in the absence of disease progression evidenced by radiological evaluation, regardless | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • OS; • ORR, DCR, DoR, and TTP evaluated by BIRC; • ORR, DCR, DoR, and TTP evaluated by investigator; • PFS evaluated by investigator; • PFS2 evaluated by investigator. • Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) judged in accordance with NCI-CTCAE v5.0; vital signs, ECG and abnormal laboratory values. • Changes from baseline in all PRO-CTC AE GI related items; • Symptoms related to NSCLC, including cough, dyspnea, and pain, assessed using EORTC QLQ-C30 and the QLQ-LC13 to evaluate the health-related quality of life (HRQoL) and NSCLC-related symptoms. To compare the proportion of subjects with improved status, time to deterioration, and scores (mean value and mean changes from baseline) in pyrotinib versus docetaxel treatment arms. • Plasma concentrations of pyrotinib.;Timepoint(s) of evaluation of this end point: OS will be collected on Day 1 of each dosing cycle, at discontinuation of treatment/withdrawal, at safety follow-up: 28 days (±7) after the last dose and at Survival follow-up (comes after safety followup). Every 56 days (±7 days) after the last dose investigators must follow up subject’s survival via phone calls. The definition of the Follow-up period is: in addition to safety follow-up and survival follow-up, in the absence of disease progression evidenced by radiological evaluation, regardless whether subjects discontinue from study treatment or not, subjects still need to receive radiological evaluations according to the scheduled visits, until BIRC assessed progression of disease, death, lost to follow up, consent withdrawal, study termination by the sponsor (whichever occurs first). | — |
Countries
Australia, Belgium, China, France, Germany, Italy, Korea, Republic of, Spain, Taiwan, United States
Contacts
Public ContactAssist. Director Clinical Operation
Jiangsu Hengrui Medicine Co., Ltd.
Outcome results
None listed