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Z. Piotrowska



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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
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      P2.06-007 - A Phase 1/2 Trial of the Oral EGFR/HER2 Inhibitor AP32788 in Non–Small Cell Lung Cancer (NSCLC) (ID 5047)

      14:30 - 14:30  |  Author(s): Z. Piotrowska

      • Abstract

      Background:
      Approximately 4%–9% of EGFR-mutated NSCLC tumors have EGFR exon 20 insertion mutations, and no targeted treatment options are currently approved for patients with these mutations. In addition, approximately 2%–4% of patients with NSCLC have HER2 mutations, the majority of which are exon 20 insertion mutations. The irreversible EGFR/HER2 inhibitor AP32788 was designed to selectively inhibit EGFR or HER2 kinases with EGFR/HER2 exon 20 mutations. In preclinical studies, investigational agent AP32788 had potent inhibitory activity against all EGFR and HER2 mutants tested, including exon 20 insertion mutants, while sparing wild-type EGFR.

      Methods:
      This phase 1/2 trial is a first-in-human, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of orally administered AP32788 (NCT02716116). The study will be conducted in 2 parts: a dose-escalation phase with a 3+3 design and an expansion phase of 4 histologically and molecularly defined cohorts after the recommended phase 2 dose (RP2D) is determined. Patients (≥18 years) must have locally advanced or metastatic NSCLC. In phase 1, the dose-escalation phase, patients refractory to standard available therapies will be enrolled. The primary endpoint of phase 1 is identification of the RP2D of AP32788. Secondary endpoints include safety, dose-limiting toxicities, maximum tolerated dose, and plasma pharmacokinetics. Expected phase 1 enrollment is 20–30 patients. In phase 2, the expansion phase, 4 cohorts will be enrolled, patients with: 1. EGFR exon 20 activating insertions, without active, measurable CNS metastases; 2. HER2 exon 20 activating insertions or point mutations, without active, measurable CNS metastases; 3. EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases; 4. other targets against which AP32788 has demonstrated preclinical activity (eg, EGFR exon 19 deletions or exon 21 substitutions [with/without the T790M mutation] and other uncommon activating mutations in EGFR). The primary endpoint of phase 2 is investigator-assessed objective response rate (ORR) per RECIST v1.1 for all expansion cohorts except Expansion Cohort 3, for which the primary endpoint is intracranial ORR. Phase 2 secondary endpoints include safety, pharmacokinetics, and additional efficacy assessments (ORR per independent review committee, best overall response, best target lesion response, duration of response, disease control rate, progression-free survival, and overall survival; for Expansion Cohort 3: duration of intracranial response and intracranial progression-free survival). Expected phase 2 enrollment is 80 patients (total). The first patient was enrolled in phase 1 in June 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
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      P3.02b-115 - Clinical Activity of Osimertinib in EGFR Mutation Positive Non Small Cell Lung Cancer (NSCLC) Patients (Pts) Previously Treated with Rociletinib (ID 4893)

      14:30 - 14:30  |  Author(s): Z. Piotrowska

      • Abstract

      Background:
      Both osimertinib and rociletinib were developed to target the EGFR resistance mutation T790M. Sequist, et al reported clinical activity with osimertinib in 9 pts previously treated with rociletinib[1]. We conducted a retrospective analysis at 8 institutions of pts treated with rociletinib, who discontinued the drug due to disease progression or intolerable toxicity and subsequently received osimertinib.

      Methods:
      We identified pts treated with rociletinib followed by osimertinib, as part of osimertinib's US expanded access program or via commercial supply. Clinical characteristics and outcomes were assessed. Frequency of clinical and radiologic assessments on osimertinib was at the discretion of the treating physician. For this retrospective review, reverse KM method was used to calculate the median follow-up; KM method was used for time-to-event endpoints.

      Results:
      45 pts were included in this analysis. Median age at the start of osimertinib was 66 years (43-86) and 71% were female. 28 pts had exon 19 deletions and 16 had L858R. Median duration of therapy on front line EGFR TKI was 18 months (5-54). Median starting dose of rociletinib was 625 mg bid (range 500-1000). The response rate (RR) and disease control rate (DCR; Response+Stable Disease) with rociletinib were 38% and 91%; median duration of rociletinib therapy was 6.2 months. 32 (71%) pts discontinued rociletinib for disease progression. 23 (51%) pts received other therapies (1-4) before starting osimertinib. 25 (56%) pts were known to have brain metastases at osimertinib initiation. RR and DCR with osimertinib were 33% and 82%. DCR in the brain was 88%. With a median follow-up of 7.1 months, median duration of osimertinib therapy in all patients was 8 months (95%CI- 6.6-NR; 64% censored). The 1-year overall survival (OS) rate on osimertinib was 70% (54%-91%). In the 32 pts who discontinued rociletinib due to progression, DCR with osimertinib was 75% and median duration of therapy was 7.8 months (4.6-NR). Neither duration of,or response to rociletinib treatment, nor interval between the two the drugs was associated with duration of osimertinib or OS after osimertinib using a Cox model adjusted for age and sex.

      Conclusion:
      Osimertinib can provide clinical benefit in EGFR mutation positive NSCLC patients previously treated with rociletinib. The clinical activity of osimertinib in these patients may be related to more potent inhibition of T790M mutation or ability to overcome resistance to rociletinib. Reference- 1. Sequist, et al. JAMA Oncology 2016