There are 14 clinical trials
This study will test if local therapies in addition to erlotinib can improve responses and delay the time until new treatment is required. This study will also collect blood samples for research blood tests.
At least five patients will need to complete local therapy within 2 years of the study being open to accrual for the primary endpoint to be met.. Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A --- --- L861Q --- --- S768I ---
- Any medical co-morbidities that would preclude surgery or radiation therapy Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A --- --- L861Q --- --- S768I ---
Description: At least five patients will need to complete local therapy within 2 years of the study being open to accrual for the primary endpoint to be met.
Measure: Feasibility as Measured by at Least Five Patients Will Need to Complete Local Therapy. Time: 2 yearsPhase II trial to evaluate trametinib in patients with locally advanced non-squamous, non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with progressive disease on at least one prior line of therapy.
bevacizumab, ipilumimab) 4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). --- G719A --- --- S768I ---
Description: The ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence from the start of treatment.
Measure: Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: The DR for Complete Response (CR) and Partial Response (PR) will be measured from the date that the best response is first recorded until the date that PD is documented. For patients who continue treatment post progression, the date of Disease Progression (PD) documentation will be used for analysis.
Measure: Duration of Response (DR) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: DCR will be defined as the percentage of patients who have achieved CR, PR, or Stable Disease (SD) for at least 12 weeks.
Measure: Disease Control Rate (DCR) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause over a period of 1 year. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis.
Measure: Progression Free Survival (PFS) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstDescription: OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause over a period of 1 year.
Measure: Overall Survival (OS) according to RECIST Version 1.1 criteria. Time: From start of treatment up to 4 years, or until disease progression, whichever comes firstIn recent years, with the progress in the treatment field, Non-Small Cell Lung Cancer(NSCLC) has become the most successful cancer species in precision medicine. Patients with positive driving genes such as EGFR, ALK, ROS1, BRAF and so on have clearly targeted drugs, which bring survival benefits to patients.However, about 50% of patients still lack a clear driving gene target, which has become the focus of current research.In the field of wild-type NSCLC with negative driver genes, the classic first-line treatment regimen is the two-drug regimen containing platinum.The study by Kimura T in the first-line treatment of 54 wild-type advanced NSCLC patients with carboplatin and pemetrexed showed that the ORR, mPFS and mOS of patients with wild-type non-squamous NSCLC treated with carboplatin permetrexine were 35.8%, 5.4 months and 12.7 months respectively. Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development.In the phase Ⅲ study, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.46 months, the placebo group PFS and OS were 1.4 months and 6.37 months. The efficacy and safety of Anlotinib combined with Pemetrexed and Carboplatin followed by maintenance therapy with Anlotinib plus Pemetrexed as the first-line treatment in patients with advanced nonsquamous NSCLC deserve further exploration.
Exclusion Criteria: - Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer),Lung sarcomatoid carcinoma; - Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma; - Patients with pathological fracture in bone metastasis of non-small-cell lung cancer; - Tumor histology or cytology confirmed EGFR mutagenesis [EGFR sensitive mutations include 18 exon point mutations (G719X), 19 exon deletions, 20 exon S768I mutations and 21 exon point mutations (L858R and L861Q)] and ALK gene rearrangement positivity, include EGFR/ALK status cannot be determined for various reasons; - Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor; - Medical history and combined history： 1. Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 28 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms and metastases in midbrain, pons, cerebellum, medulla oblongata, or spinal cord, brain metastases and local radiotherapy after two weeks to allow group); 2. The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks; 3. Had malignant tumors except NSCLC within 5 years before enrollment(except for patients with cervical carcinoma in situ , basal cell or squamous cell skin cancer who have undergone a curative treatment, local prostate cancer after radical resection, ductal carcinoma in situ or papillary thyroid cancer after radical resection); 4. Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;Note: Under the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes; 5. Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g; 6. --- S768I ---
Description: PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
Measure: Progression-free survival，PFS Time: each 42 days up to PD or death(up to 24 months)Description: ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
Measure: Objective Response Rate,ORR Time: each 42 days up to intolerance the toxicity or PD (up to 24 months)Description: Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Measure: Disease Control Rate,DCR Time: each 42 days up to intolerance the toxicity or PD (up to 24 months).Description: Defined as the time until death due to any cause.
Measure: Overall Survival,OS Time: each 42 days up to intolerance the toxicity or PD (up to 24 months) .Description: Number of Participants with Adverse Events.
Measure: Safety(Number of Participants with Adverse Events ) Time: each 42 days up to intolerance the toxicity or PD (up to 24 months).Anlotinib which has shown an affirmatory efficacy in ALTER0303 controlled trial as a 3rd-line treatment on advanced NSCLC is a tyrosine kinase inhibitor with a favorable safety profile in phase I trial which mainly targets VEGFR1/2/3, FGFR, PDGFR and c-kit. The purpose of this trail is to establish whether advanced non-squamous NSCLC patients could benefit from the combination treatment of docetaxel, carboplatin and anlotinib as the first-line and maintenance treatment.
Exclusion Criteria: - Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer), Lung sarcomatoid carcinoma; - Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma; - Patients with pathological fracture in bone metastasis induced by non-small-cell lung cancer; - Tumor histology or cytology confirmed EGFR mutagenesis [EGFR sensitive mutations include 18 exon point mutations (G719X), 19 exon deletions, 20 exon S768I mutations and 21 exon point mutations (L858R and L861Q)] and ALK gene rearrangement positivity, include EGFR/ALK status cannot be determined for various reasons; - Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor; Medical history and combined history： - Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 28 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms and metastases in midbrain, pons, cerebellum, medulla oblongata, or spinal cord, brain metastases and local radiotherapy after two weeks to allow group); - The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks; - Had malignant tumors except NSCLC within 5 years before enrollment(except for patients with carcinoma in situ of the cervix , basal cell or squamous cell skin cancer who have undergone a curative treatment, local prostate cancer after radical resection, ductal carcinoma in situ or papillary thyroid cancer after radical resection); - Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy; Note: Under the condition of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes; - Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g; - The effects of surgery or trauma have been eliminated for less than 14 days before enrollment in subjects who have undergone major surgery or have severe trauma; - Severe acute or chronic infections requiring systemic treatment; Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) <50%; - There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma; - Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment; Long-term unhealed wounds or fractures; - Decompensated diabetes or other ailments treated with high doses of glucocorticoids; - Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction; - Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis; - Events of venous/venous thrombosis occurring within the first 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; - Physical examination and laboratory findings: 1. --- S768I ---
Description: Clinical response of treatment according to RESIST v1.1 criteria (PFS, progression-free survival)
Measure: progression-free survival Time: Estimated about 24 months.Description: Clinical response of treatment according to RESIST v1.1 criteria (OS, overall survival)
Measure: Overall Survival Time: Estimated about 24 months.Description: Clinical response of treatment according to RESIST v1.1 criteria (DCR, disease control rate)
Measure: Disease Control Rate Time: Estimated about 24 months.Description: Clinical response of treatment according to RESIST v1.1 criteria (ORR, Overall Response Rate)
Measure: Overall Response Rate Time: Estimated about 24 months.This is one randomized, double-blind, placebo-controlled, multi-center, phase III clinical study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with standard 1st-line chemotherapy in treatment-naïve advanced non-small cell lung cancer (NSCLC); and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population. About 450 subjects with advanced non-small cell lung cancer without activated EGFR mutation (exon 19 deletion, or exon 21 L858R, exon 21 L861Q, exon 18 G719X or exon 20 S768I mutations) and ALK fusion will be 2:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors: PD-L1 expression (TC≥1% vs TC＜1%); Smoking state (often smoking vs no smoking or infrequent smoking); Pathological type (squamous cell carcinoma vs non-squamous cell carcinoma).
About 450 subjects with advanced non-small cell lung cancer without activated EGFR mutation (exon 19 deletion, or exon 21 L858R, exon 21 L861Q, exon 18 G719X or exon 20 S768I mutations) and ALK fusion will be 2:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. --- L858R --- --- L861Q --- --- S768I ---
Description: Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1)
Measure: PFS Time: Up to 2 approximately yearsDescription: Overall survival (OS)
Measure: OS Time: Up to 2 approximately yearsDescription: PFS evaluated by the Blinded Individual Review Committee (BIRC) based on RECIST1.1 criteria
Measure: PFS Time: Up to 2 approximately yearsDescription: Objective response rate (ORR) evaluated by investigators and BIRC based on RECIST1.1
Measure: ORR Time: Up to 2 approximately yearsDescription: Duration of response (DOR) evaluated by investigators and BIRC based on RECIST1.1
Measure: DOR Time: Up to 2 approximately yearsDescription: Disease control rate (DCR) evaluated by investigators and BIRC based on RECIST1.1
Measure: DCR Time: Up to 2 approximately yearsDescription: Time to response (TTR) evaluated by investigators and BIRC based on RECIST1.1
Measure: TTR Time: Up to 2 approximately yearsDescription: Overall incidence of adverse events (AEs); incidence of grade 3 and above AEs; incidence of serious adverse events (SAEs); incidence of AEs leading to termination of the investigational drug; incidence of AEs interruption of the investigational drug
Measure: Incidence of AEs/SAEs Time: From date of consent informed until 60 days after the last investigational product administration. Up to 2 approximately yearsThe study is designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of EGF816 in combination with INC280 and to estimate the preliminary anti-tumor activity of EGF816 in combination with INC280 in patients with advanced non-small cell lung cancer (NSCLC) with documented EGFR mutation.
L861Q, G719X, S768I) - Presence of at least one measurable lesion according to RECIST v.1.1 - ECOG performance status ≤1 - Patients must be screened for HBV. --- L861Q --- --- S768I ---
Description: ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) determined by Blinded Independent Review Committee (BIRC) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure: Phase II Groups 1, 2 and 3: Overall Response Rate per RECIST 1.1 Time: At least 24 weeksDescription: Frequency of treatment-emergent adverse events
Measure: Phase II Group 4 Incidence and severity of AEs/SAEs, dose interruptions, reductions and dose intensity Time: At least 24 weeksDescription: Assessment of the safety of EGF816 in combination with INC280 will be performed continuously during the treatment phase and 30 days after discontinuation of the study treatment
Measure: Safety of INC280 and EGF816: Incidence and severity of AEs and SAEs, including changes in hematology and chemistry values, vital signs and ECGs (Phase I/II) Time: At least 24 weeksDescription: Assessment of the tolerability of EGF816 in combination with INC280 will be performed continuously during the treatment phase and 30 days after discontinuation of the study treatment
Measure: Frequency of dose interruption, frequency of reduction and dose intensity (Phase I/II) Time: At least 24 weeksDescription: ORR is defined as proportion of patients with best overall response of (PR+CR) determined by Investigator assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure: Overall Response Rate (Phase Ib and Phase II Group 4) Time: At least 24 weeksDescription: DCR is defined as the proportion of patients with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure: Disease Control Rate (Phase I/II) Time: At least 24 weeksDescription: Progression-free survival (PFS). PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1
Measure: Progression Free Survival (Phase I/II) Time: At least 24 weeksDescription: DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1
Measure: Duration of Response (Phase I/II) Time: At least 24 weeksDescription: OS is defined as the time from first dose of the study treatment to the date of death due to any cause.
Measure: Overall Survival (Phase I/II) Time: At least 24 weeksDescription: TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure: Time to Response (Phase I/II) Time: At least 24 weeksThis is a research study to find out if a drug called, osimertinib, is safe and effective in treating advanced Non-Small Cell Lung Cancer (NSCLC) by targeting the treatment of epidermal growth factor receptor (EGFR) mutation exon 18 G719X, exon 20 S7681, or exon 21 L861Q. Patients on the study will not have had previous tyrosine kinase inhibitor (TKI) treatment.
Overall survival as noted by follow-up via composite of telephone or medical record review.. Overall survival as defined as time from starting study therapy until death from any causes.. Inclusion Criteria: - EGFR mutations as performed on a CLIA certified laboratory demonstrating EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q. --- S768I ---
- Grade ≥ 2 blurred vision, conjunctivitis, corneal ulcer, dry eye, or keratitis Inclusion Criteria: - EGFR mutations as performed on a CLIA certified laboratory demonstrating EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q. --- S768I ---
Description: RECIST 1.1 will be used to measure confirmed partial or complete responses to the study drug.
Measure: Objective response rate as assessed by the investigator using Response Evaluation Criteria In Solid Tumors RECIST 1.1 (brand name) Time: Up to 3 yearsDescription: Progression will be defined as time from starting study therapy to disease progression or death (whichever occurs first)
Measure: Progression free survival as measured by Response Evaluation Criteria In Solid Tumors RECIST 1.1 (brand name) as assessed by the investigator. Time: Up to 5 yearsDescription: Evaluation of safety using the National Cancer Institute (NCI) CTCAE version 4.03
Measure: AEs as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Time: Up to 3 yearsDescription: Overall survival as defined as time from starting study therapy until death from any causes.
Measure: Overall survival as noted by follow-up via composite of telephone or medical record review. Time: Up to 5 yearsThis study is a multi-center, open-label, dose-finding phase Ib clinical study with extension phase, which is aimed at evaluating the efficacy and safety of GB226 combined with fruquintinib in treatment of relapsed or metastatic NSCLC patients with EGFR-sensitive mutations who have failed to respond to EGFR-TKI treatment,evaluating the pharmacokinetic characteristics of GB226 and fruquintinib, and the immunogenicity of GB226, and preliminarily evaluating the antitumor activity of GB226 and fruquintinib.
Inclusion Criteria: 1. Aged 18-75 years, male or female; 2. Understanding the procedures and contents of the study, and voluntarily signing the written informed consent form; 3. Histologically or cytology confirmed relapsed or metastatic NSCLC; 4. EGFR gene sensitive mutation is confirmed positive, any of following is met: exon 19 deletion (19DEL), exon 21 point mutation (L858R / L861Q), 18 exon point mutation (G719X), 20 exon point mutation (S768I). --- L858R --- --- L861Q --- --- S768I ---
Description: Assessment of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Measure: Incidence of Adverse Event Time: all adverse events will be recorded from the time the consent form is signed through 90 days following cessation of treatment.Description: Assessment of serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Measure: Incidence of Serious Adverse Event Time: all adverse events will be recorded from the time the consent form is signed through 90 days following cessation of treatment.Description: Incidence of Dose Limited Toxicity
Measure: Dose Limited Toxicity Time: Day 1 to Day 28 after first doseDescription: Defined as the highest dose tested in which only 0 or 1 out of 6 evaluable patients experience a dose limiting toxicity, as graded by the National Cancer Institute (NCI) Common terminology Criteria for Adverse Events (CTCAE) version 4.03
Measure: Maximum Tolerated Dose Time: Day 1 to Day 28 after first doseDescription: Objective response rate in accordance with RECIST 1.1. ORR will be calculated as the percent of patients in each of the expansion cohorts whose best confirmed response is complete response (CR) or partial response (PR).
Measure: ORR Time: up to 52 weeksDescription: Progression-free survival. From start of treatment to time of progression or death, whichever occurs first
Measure: PFS Time: up to 52 weeksDescription: Duration of Response. Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause.
Measure: DOR Time: up to 52 weeksDescription: Disease control rate.DCR will be the proportion of patients in each of the expansion cohorts whose best confirmed response is CR, PR, or stable disease (SD).
Measure: DCR Time: up to 52 weeksDescription: Overall Survival. From start of treatment to time of death.
Measure: OS Time: up to 52 weeksDescription: incidence of anti-GB226 antibody(ADA)
Measure: ADA Time: up to 52 weeksDescription: Pharmacokinetics of GB226 and Fruquinitinib by assessment of Cmax
Measure: Cmax Time: up to 16 weeksDescription: Pharmacokinetics of GB226 and Fruquinitinib by assessment of AUC
Measure: AUC Time: up to 16 weeksThis is a phase 2 single-arm, non-randomized multicentre and tissue acquisition study to evaluate acquired resistance mechanisms, efficacy, and safety in advanced, EGFR tyrosine kinase inhibitor-naïve NSCLC patients with EGFR-activating mutations who receive a first-line osimertinib orally at a dose of 80mg once daily.
Acquired resistance to first-line osimertinib is mediated by heterogeneous mechanisms including MET amplification (15%), secondary EGFR mutation including C797S or S768I (7%), PIK3CA mutation (7%), CDK4/6 amplification (5%), KRAS mutation (3%), BRAF mutation (3%), CCND1-3 amplification (3%), CCNE1 amplification (2%), HER2 amplification (2%), and SPTBN1-ALK fusion (1%) using plasma genotyping of FLAURA study (N=91). --- C797S --- --- S768I ---
Description: Disease progression as defined by investigator assessments according to RECIST1.1
Measure: Proportion of acquired resistance mechanisms to osimertinib at disease progression Time: Through study completion, an average of 2 yearsDescription: AEs/SAEs as defined by NCI CTCAE version 5.0
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: Through study completion, an average of 2 yearsDescription: PFS as defined as the time from the date of initiation until the date of first documented progression
Measure: Progression-Free Survival (PFS) Time: Through study completion, an average of 2 yearsDescription: OS as defined as the time from the date of first dose until death due to any cause
Measure: Overall Survival (OS) Time: Through study completion, an average of 2 yearsDescription: ORR using investigator assessments according RECIST1.1
Measure: Objective Response Rate (ORR) Time: Through study completion, an average of 2 yearsGefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Results from two randomised phase II trials (IDEAL 1 and 2) suggested that gefitinib was efficacious and less toxic, compared with previous results, than was chemotherapy in patients with previously-treated non-small-cell lung cancer. Two phase III trials of gefitinib in advanced non-small-cell lung cancer followed on from the IDEAL phase II studies: Iressa Survival Evaluation in Lung cancer (ISEL) and Iressa NSCLC Trial Evaluating REsponse and Survival versus Taxotere (INTEREST). Although the phase III ISEL trial failed to prove the superiority of gefitinib treatment compared to placebo in previously treated patients, a subgroup analysis demonstrated improved survival in particular populations (Asians and non-smokers). The INTEREST study compared an EGFR tyrosine kinase inhibitor with chemotherapy in pretreated advanced non-small-cell lung cancer. In INTEREST, survival was similar for gefitinib and docetaxel in almost all subgroups; no EGFR-related biomarker or any clinical factor (including female sex, adenocarcinoma histology, never-smoker, and Asian ethnicity) appeared to be predictive of a greater survival benefit for gefitinib versus docetaxel. However, these factors may still be predictive of a greater survival benefit for gefitinib and/or docetaxel versus best supportive care; alternatively, they may just be good prognostic factors. Progression free survival and overall response rate was no statistically significant difference between gefitinib and docetaxel. This suggests gefitinib can provide similar overall survival to docetaxel in pretreated advanced non-small-cell lung cancer patients. These studies have demonstrated that gefitinib is effective for the second-line treatment of NSCLC. Now, gefitinib is recommended in advanced and metastatic NSCLC as second-line chemotherapy. But, there was no prospective study with gefitinib in NSCLC wih squamous cell histology. This trial will investigate the efficacy and safety of gefitinib in locally advanced, metastatic NSCLC patients with squamous cell histology who have failed first-line chemotherapy.
Presence of EGFR mutation reported to confer resistance to EGFR TKI: exon 20 point mutation (T790M or S768I EGFR) or exon 20 insertion 11. --- T790M --- --- S768I ---
Description: safety & tolerability: NCI CTCAE version 4.0
Measure: number of participants with adverse events as a measure of safety and tolerability Time: 2 yearsUntil recently, the first line treatment of metastatic Non Small Cell Lung Cancer (NSCLC) was a platine-based chemotherapy. It has been changed by the discovery of EGFR (Epidermal Growth Factor Receptor) mutations and associated treatment with Tyrosine Kinase Inhibitor (TKI) of EGFR. The superiority of EGFR TKI over chemotherapy for EGFR mutated patients has been proved in several phase III trials with gefitinib, erlotinib or afatinib. Nevertheless, all patients will progress after 9 to 12 months of treatment due to the appearance of a treatment resistance. Afatinib is an irreversible EGFR TKI. It binds to its receptor permanently.Contrary to erlotinib and gefitinb which inhibits only EGFR, afatinib inhibits the kinase activity of all HER family (Human Epidermal growth factor Receptor). Nevertheless, there is no proof that afatinib delay the appearance of resistance. Cetuximab is a monoclonal antibody which binds specifically with EGFR. The double inhibition of EGFR by afatinib and cetuximab has demonstrated its efficacy in pre-clinical models. The hypothesis of this study is that the combination between cetuximab and afatinib will permit to delay or decrease the appearance of resistances.
Principal Inclusion Criteria: - Stage III or IV NSCLC, non irradiable non operable - Non squamous NSCLC histologically or cytologically confirmed - No previous treatment of NSCLC - EGFR mutation (exon 19 deletion, L858R mutation, G719X , L861Q or S768I mutations or exon 19 insertion) - Presence of at least one lesion that can be measured - PS 0 or 1 Principal Exclusion Criteria: - Symptomatic brain metastasis or requiring immediate radiotherapy - T790M mutation or exon 20 insertion - Radiotherapy less than 2 weeks prior randomization including symptomatic radiotherapy - Interstitial pneumopathy Principal Inclusion Criteria: - Stage III or IV NSCLC, non irradiable non operable - Non squamous NSCLC histologically or cytologically confirmed - No previous treatment of NSCLC - EGFR mutation (exon 19 deletion, L858R mutation, G719X , L861Q or S768I mutations or exon 19 insertion) - Presence of at least one lesion that can be measured - PS 0 or 1 Principal Exclusion Criteria: - Symptomatic brain metastasis or requiring immediate radiotherapy - T790M mutation or exon 20 insertion - Radiotherapy less than 2 weeks prior randomization including symptomatic radiotherapy - Interstitial pneumopathy Non Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- L858R --- --- L861Q --- --- S768I ---
Principal Inclusion Criteria: - Stage III or IV NSCLC, non irradiable non operable - Non squamous NSCLC histologically or cytologically confirmed - No previous treatment of NSCLC - EGFR mutation (exon 19 deletion, L858R mutation, G719X , L861Q or S768I mutations or exon 19 insertion) - Presence of at least one lesion that can be measured - PS 0 or 1 Principal Exclusion Criteria: - Symptomatic brain metastasis or requiring immediate radiotherapy - T790M mutation or exon 20 insertion - Radiotherapy less than 2 weeks prior randomization including symptomatic radiotherapy - Interstitial pneumopathy Principal Inclusion Criteria: - Stage III or IV NSCLC, non irradiable non operable - Non squamous NSCLC histologically or cytologically confirmed - No previous treatment of NSCLC - EGFR mutation (exon 19 deletion, L858R mutation, G719X , L861Q or S768I mutations or exon 19 insertion) - Presence of at least one lesion that can be measured - PS 0 or 1 Principal Exclusion Criteria: - Symptomatic brain metastasis or requiring immediate radiotherapy - T790M mutation or exon 20 insertion - Radiotherapy less than 2 weeks prior randomization including symptomatic radiotherapy - Interstitial pneumopathy Non Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- L858R --- --- L861Q --- --- S768I --- --- T790M --- --- L858R --- --- L861Q --- --- S768I ---
The purpose of this phase 1/2 study is to evaluate the safety, recommended phase 2 dose (RP2D), dose limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics of oral TAK-788, anti-tumor activity of TAK-788 in participants with NSCLC with epidermal growth factor receptor (EGFR) or human epidermal growth factor 2 (HER2), and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations, and to explore relationship between tumor and/or plasma biomarkers, and TAK-788 efficacy, safety, and/or cytochrome P450 3A (CYP3A) induction. The study will also determine the efficacy of TAK-788 in participants with locally advanced metastatic NSCLC harboring EGFR in-frame exon 20 insertion mutations who have received at least 1 prior line of therapy for locally advanced or metastatic NSCLC.
Part 2: Expansion Cohort 4 Specific Inclusion Criteria: 1. Have one of the following documented by a local test: an activating mutation in EGFR including exon 19 deletions or exon 21 L858R substitution (with or without T790M), or an uncommon activating mutation other than exon 20 insertion including, but not limited to, G719X (where X is any other amino acid), S768I, L861Q, or L861R. --- L858R --- --- T790M --- --- S768I ---
To tested if the adding of consolidative SBRT to TKI in EGFR mutated patients with less than or equal to 5 metastatic sites (primary + 5) will improve progression free survival (PFS) compared to TKI alone.
To evaluate overall survival after SBRT followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.. Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A --- --- L861Q --- --- S768I ---
- Any medical co-morbidities that would preclude surgery or radiation therapy Inclusion Criteria: - Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion): - all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology - all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion. --- L858R --- --- G719A --- --- L861Q --- --- S768I ---
Description: Evaluate the effect of TKI with or without SBRT on progression free survival
Measure: Progression free survival Time: 4 yearsDescription: To describe local control and out-of-field disease progression
Measure: local control Time: 4 yearsDescription: To evaluate overall survival after SBRT followed by maintenance chemotherapy in comparison to maintenance chemotherapy alone.
Measure: Overall survival Time: 4 yearsThe purpose of this study is to test whether the combination of bevacizumab and erlotinib can prolong progression free survival as compared with erlotinib alone as first-line treatment in patients with non small cell lung cancer (NSCLC) with activating mutation of EGFR.
Inclusion Criteria: 1. Age ≥18 years 2. Histological documentation of primary non squamous lung carcinoma 3. Stage IV or IIIB disease with supraclavicular metastatic nodes (according to TNM 7th edition) 4. Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R mutation or other activating/sensitizing mutations, such as exon 21 L861Q, exon 18 G719S, G719A and G719C, exon 20 S768I and V769L). --- L858R --- --- L861Q --- --- G719S --- --- G719A --- --- G719C --- --- S768I ---
Description: as determined by investigator
Measure: progression free survival Time: up to 2 yearsDescription: as determined by an independent central review board blinded to study treatment
Measure: progression free survival Time: up to 2 yearsDescription: samples taken at baseline, 6 weeks, 6 months, and at progression
Measure: number and type of EGFR mutations in plasma samples Time: up to 2 years