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D.H. Lee
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-021 - Efficacy and Safety of ASP8273 versus Erlotinib or Gefitinib as First-Line Treatment in Subjects with EGFR<Sup>Mut+</Sup> NSCLC (ID 4148)
14:30 - 14:30 | Author(s): D.H. Lee
- Abstract
Background:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown antitumor efficacy and prolonged progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) harboring EGFR activation mutations; however, acquired resistance often develops limiting clinical efficacy. ASP8273 is an irreversible, once-daily (QD), orally available TKI with activity against both activating and resistance EGFR mutations (ex19del, L858R, T790M). Preliminary findings from Phase 1 and Phase 2 trials in the US, Japan, Taiwan, and Korea have demonstrated antitumor activity and overall tolerability of ASP8273 at doses of 100mg–300mg.
Methods:
This global, multicenter, open-label, randomized, Phase 3 study will enroll ~600 adult subjects with Stage IIIB/IV NSCLC with EGFR-activating mutations (ex19del or L858R, with or without T790M) who have not been treated with an EGFR inhibitor TKI (NCT02588261). Subjects will be randomized 1:1 to treatment with either 300mg oral ASP8273 QD or erlotinib/gefitinib. Each site will select a comparator drug (150mg erlotinib QD or 250mg gefitinib QD) at the beginning of the study. Randomization will be stratified by ECOG status (0, 1, and 2), EGFR mutation (ex19del, L858R), comparator selected (erlotinib vs gefitinib), and race (Asian vs non-Asian). Subjects will not be enrolled if they harbor both ex19del and L858R. All subjects will begin treatment on Day 1 Cycle 1 and will continue on 28-day continuous dosing cycles until the subject discontinues (eg, due to radiologic progression as determined by RECIST or unacceptable toxicity). Dose reductions will be allowed for ASP8273 and erlotinib, but not for gefitinib. The primary study objective is PFS as assessed by independent radiological review (IRR); secondary study objectives are overall survival, best overall response rate, disease control rate and duration of response by IRR, safety/tolerability, and patient quality of life. An independent Data Monitoring Committee will oversee trial safety and the interim futility analysis. Enrollment for the trial began 26 February 2016; 46 subjects have been randomized as of 17 May 2016.
Results:
Section not applicable
Conclusion:
Section not applicable
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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-117 - Phase Ib Results from a Study of Capmatinib (INC280) + EGF816 in Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) (ID 5012)
14:30 - 14:30 | Author(s): D.H. Lee
- Abstract
Background:
Among patients with EGFR-mutant NSCLC who progress on EGFR tyrosine kinase inhibitors (EGFR-TKIs), the most common (50%) resistance mechanism is secondary T790M mutation. cMET dysregulation is the second most common mechanism, with amplification occurring in 5‒22% of resistant patients. This study evaluates targeting these two mechanisms to overcome acquired resistance to EGFR-TKIs. Capmatinib (INC280) is a highly selective, potent cMET inhibitor with clinical activity in patients with cMET dysregulation. EGF816 is an irreversible EGFR-TKI that selectively inhibits T790M and EGFR-activating mutations, with antitumor activity in EGFR[T790M]-mutated NSCLC. In this open-label Phase Ib/II study, capmatinib was combined with EGF816 in patients with EGFR-mutated, EGFR-TKI resistant NSCLC.
Methods:
The Phase Ib primary objective is estimation of the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of the combination using an adaptive Bayesian logistic regression model. Eligible patients (≥18 years; ECOG PS ≤2) must have documented EGFR-mutated (exon19del and/or L858R) NSCLC and documented progression (RECIST v1.1) while on EGFR-TKI treatment. Patients received capmatinib (starting dose 200 mg BID) plus EGF816 (starting dose 50 mg QD).
Results:
At the data cut-off (Aug 1, 2016), 33 patients were enrolled at five capmatinib BID/EGF816 QD mg dose levels (200/50 [n=4]; 200/100 [n=5]; 400/75 [n=3]; 400/100 [n=16]; 400/150 mg [n=5]); 18/33 (55%) patients discontinued treatment, mainly (13 [39%] patients) due to disease progression. Dose-limiting toxicities (DLTs) occurred in 4 patients: in 1 patient at the 200/50 dose level (increased alanine aminotransferase), 1 patient at the 400/100 dose level (anaphylactic reaction), and 2 patients at the 400/150 dose level (pyrexia, maculopapular rash, and allergic dermatitis). The most frequent (≥30%) any-grade adverse events (AEs), regardless of causality, were nausea (55%), peripheral edema (45%), increased amylase (42%), increased blood creatinine (36%), decreased appetite and diarrhea (both 30%). The most frequent (>10%) Grade ≥3 AEs were maculopapular rash (18% [mainly in the 400/150 cohort]) and increased amylase (12%). Capmatinib and EGF816 exposure increased with dose; preliminary data indicate a ~35% increase in EGF816 exposure (AUC) at steady state when co-administered with the capmatinib RP2D, compared with single-agent exposure. The investigator-assessed overall response rate was 42% (2/33 complete responses; 12/33 partial responses) across all dose levels and 50% (8/16 patients) at the 400/100 dose level, regardless of molecular status of resistance.
Conclusion:
The RP2D of the combination was declared as capmatinib 400 mg BID + EGF816 100 mg QD. Preliminary antitumor activity was observed across dose levels, independent of T790M status.
