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M. Wang
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JCES01 - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 413)
- Event: WCLC 2016
- Type: Joint Chinese / English Session
- Track:
- Presentations: 1
- Moderators:F.R. Hirsch, C. Bai
- Coordinates: 12/04/2016, 08:00 - 11:45, Stolz 1
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JCES01.17 - A Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain Metastasis (ID 7059)
11:10 - 11:10 | Author(s): M. Wang
- Abstract
Background:
A significant portion of patients with non-small cell lung cancer (NSCLC) develop brain metastasis. Patients with brain metastasis suffer from poor prognosis with a median survival of less than 6 months and low quality of life with limited treatment options. First generation EGFR tyrosine kinase inhibitors (EGFR TKIs) have demonstrated significant clinical benefit for patients with EGFR-mutant NSCLC. However, their effect on brain metastasis is limited due to poor drug penetration into the brain. Epitinib is an EGFR TKI designed to improve brain penetration. A Phase I dose escalation study on epitinib has been completed and the recommended Phase 2 dose (RP2D) determined (Y-L Wu, 2016 ASCO). This Phase I dose expansion study was designed to evaluate the efficacy and safety of epitinib in EGFR-mutant NSCLC patients with brain metastasis.
Methods:
This is an ongoing open label, multi-center Phase I dose expansion study. EGFR-mutant NSCLC patients with confirmed brain metastasis, either prior EGFR TKI treated or EGFR TKI treatment naïve, were enrolled to receive oral epitinib 160 mg per day. Patients with extra-cranial disease progression while on treatment with an EGFR TKI were excluded. Tumor response was assessed per RECIST 1.1.
Results:
As of 31 May, 2016, 27 patients (13 EGFR TKI pretreated, 14 EGFR TKI treatment naïve) have been enrolled and treated with epitinib. The most frequent adverse events (AEs) were skin rash (89%), elevated ALT (41%)/AST (37%), hyper-pigmentation (41%) and diarrhea (30%). The most frequent Grade 3/4 AEs were elevations in ALT (19%), gamma-GGT (11%), AST (7%), hyperbilirubinemia (7%) and skin rash (4%). There have been no Grade 5 AEs to date. Among the 24 efficacy evaluable patients (11 TKI pretreated, 13 TKI naïve), 7 (7/24, 29%) achieved a partial response (PR), including 1 unconfirmed PR. All PRs occurred in EGFR TKI treatment naïve patients (7/13, 53.8%). Of the 24 evaluable patients, 8 (5 EGFR TKI treatment naïve, 3 EGFR TKI pretreated) had measurable brain metastasis (lesion diameter>10 mm per RECIST 1.1) with 2 PRs (both EGFR TKI treatment naïve patients, 2/5, 40%).
Conclusion:
Epitinib 160mg per day treatment in EGFR-mutant NSCLC patients with brain metastasis demonstrated clinical activity both extra- and intra-cranial. Epitinib was well tolerated. The data to date appears encouraging and warrants further development of epitinib.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-001 - A Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain Metastasis (ID 4253)
14:30 - 14:30 | Author(s): M. Wang
- Abstract
Background:
A significant portion of patients with non-small cell lung cancer (NSCLC) develop brain metastasis. Patients with brain metastasis suffer from poor prognosis with a median survival of less than 6 months and low quality of life with limited treatment options. First generation EGFR tyrosine kinase inhibitors (EGFR TKIs) have demonstrated significant clinical benefit for patients with EGFR-mutant NSCLC. However, their effect on brain metastasis is limited due to poor drug penetration into the brain. Epitinib is an EGFR TKI designed to improve brain penetration. A Phase I dose escalation study on epitinib has been completed and the recommended Phase 2 dose (RP2D) determined (Y-L Wu, 2016 ASCO). This Phase I dose expansion study was designed to evaluate the efficacy and safety of epitinib in EGFR-mutant NSCLC patients with brain metastasis.
Methods:
This is an ongoing open label, multi-center Phase I dose expansion study. EGFR-mutant NSCLC patients with confirmed brain metastasis, either prior EGFR TKI treated or EGFR TKI treatment naïve, were enrolled to receive oral epitinib 160 mg per day. Patients with extra-cranial disease progression while on treatment with an EGFR TKI were excluded. Tumor response was assessed per RECIST 1.1.
Results:
As of 31 May, 2016, 27 patients (13 EGFR TKI pretreated, 14 EGFR TKI treatment naïve) have been enrolled and treated with epitinib. The most frequent adverse events (AEs) were skin rash (89%), elevated ALT (41%)/AST (37%), hyper-pigmentation (41%) and diarrhea (30%). The most frequent Grade 3/4 AEs were elevations in ALT (19%), gamma-GGT (11%), AST (7%), hyperbilirubinemia (7%) and skin rash (4%). There have been no Grade 5 AEs to date. Among the 24 efficacy evaluable patients (11 TKI pretreated, 13 TKI naïve), 7 (7/24, 29%) achieved a partial response (PR), including 1 unconfirmed PR. All PRs occurred in EGFR TKI treatment naïve patients (7/13, 53.8%). Of the 24 evaluable patients, 8 (5 EGFR TKI treatment naïve, 3 EGFR TKI pretreated) had measurable brain metastasis (lesion diameter>10 mm per RECIST 1.1) with 2 PRs (both EGFR TKI treatment naïve patients, 2/5, 40%).
Conclusion:
Epitinib 160mg per day treatment in EGFR-mutant NSCLC patients with brain metastasis demonstrated clinical activity both extra- and intra-cranial. Epitinib was well tolerated. The data to date appears encouraging and warrants further development of epitinib.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-096 - Osimertinib (AZD9291) in Asia-Pacific Patients with T790M Mutation-Positive Advanced NSCLC: Open-Label Phase II Study Results (ID 4282)
14:30 - 14:30 | Author(s): M. Wang
- Abstract
Background:
Osimertinib (AZD9291) is an oral, potent, irreversible EGFR-TKI, selective for both EGFR-sensitizing (EGFRm) and T790M resistance mutations. Following positive outcomes from recent Phase I and II trials, osimertinib is now recommended for patients with EGFR T790M mutation-positive advanced non-small cell lung cancer (aNSCLC).
Methods:
AURA17 (NCT02442349) is an open-label, single arm, Phase II study investigating the efficacy and safety of osimertinib in an Asia-Pacific patient population with EGFRm T790M mutation-positive locally advanced or metastatic NSCLC, who had progressed following EGFR-TKI therapy or EGFR-TKI and chemotherapy. T790M-positive status was confirmed via central testing of biopsy samples using the cobas[®] EGFR Mutation Test. Inclusion required measureable disease, performance status (PS) 0/1, and acceptable organ function; asymptomatic brain metastases were allowed. Patients received osimertinib 80 mg once daily until disease progression. The primary endpoint was objective response rate (ORR) according to RECIST 1.1 (by blinded independent central review, BICR). Secondary objectives included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival, and safety and tolerability.
Results:
As of 4 March 2016 data cut-off, 171 patients were enrolled, with 166 evaluable for response: median age, 60.0 years; female, 69%; Asian, 98%; never smokers, 78%; PS 0/1, 15%/85%; EGFR Exon 19 and L858R mutations, 64% and 34% patients, respectively; second-/≥third-line, 32%/68%; median treatment exposure, 5.6 months. Confirmed ORR and DCR (95% CI) by BICR were 60% (52, 68) and 88% (82, 92), respectively. DoR and PFS are not calculable as data is immature. Causally-related adverse events (AEs) grade ≥3 were reported in eight (5%) patients. AEs leading to dose interruption or dose reduction occurred in seven (4%) and two (1%) patients, respectively. Six (4%) patients discontinued treatment due to AEs, two (1%) causally-related AEs as assessed by investigator. The most commonly reported AEs (%, [grade ≥3]) were diarrhoea (29%, [0]), rashes and acnes (grouped terms) (20%, [0]), and dry skin (grouped terms) (17%, [1%]). Interstitial lung disease-like events were reported in three (2%) patients.
Conclusion:
AURA17 demonstrated clinical efficacy of osimertinib in Asia-Pacific patients with EGFR T790M mutation-positive aNSCLC, with an ORR of 60% and DCR of 88% that are comparable to global Phase II trials. Osimertinib was well tolerated, with a low frequency of AEs grade ≥3. No new safety signals were seen and the pattern of AEs was consistent with global studies
