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Maggie Sawczak



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-54 - A Phase I/Ib Study of Binimetinib (MEK162), a MEK Inhibitor Plus Carboplatin/Pemetrexed in Non-Squamous NSCLC (ID 14205)

      16:45 - 18:00  |  Author(s): Maggie Sawczak

      • Abstract

      Background

      MEK remains an important potential target in RAS/RAF dependent tumours. Binimetinib (MEK16) is a highly selective oral inhibitor of MEK1/2, which has shown activity in melanoma and other cancers. Data from preclinical models suggest greater activity with intermittent versus continuous dosing of MEK inhibitors when added to chemotherapy. This dose escalation study combines intermittent binimetinib with pemetrexed plus carboplatin in chemotherapy naive patients with advanced non-squamous NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A standard 3+3 dose-escalation design was used with planned dose expansion at RP2D (N=30) in genotypically defined cohorts (KRAS G12C mutant (mt), non-G12C mt and wild type). The primary endpoint was to define the RP2D of binimetinib using an intermittent dosing schedule in combination with standard doses of pemetrexed and carboplatin. Secondary objectives included safety, pharmacokinetics (PK), response and exploring potential biomarkers of response or toxicity. Binimetinib (30-45 mg BID) was commenced on day 1 cycle 1 for 5 days followed by a 48-hour washout period. If well tolerated, pemetrexed/carboplatin (500 mg/m2/AUC 5 mg*min/mL) were added on day 8 cycle 1 and binimetinib resumed from days 8-26 with a 48 hour drug washout before cycle 2. For subsequent cycles, pemetrexed/carboplatin were administered on day 1, binimetinib on days 1-19 every 21 days. Key eligibility criteria included ECOG performance status 0-1, adequate organ function, measureable disease by RECIST and no active CNS metastasis. Patients with EGFR/ALK mt lung cancer were permitted in the dose escalation phase after progression on standard TKI therapy.

      4c3880bb027f159e801041b1021e88e8 Result

      Between 03/2017 and 04/2018, 11 patients have been enrolled in 2 dose escalation cohorts (4 KRAS mt, 4 EGFR mt including 1 ex20ins). Six patients were treatment-naive, 3 received prior EGFR TKI and 2 prior pembrolizumab. To date, 7 have experienced grade 3 adverse events (AEs) deemed at least possibly related to binimetinib (anemia, neutropenia, abdominal pain, diarrhea, nausea, vomiting, fatigue, transaminitis). No grade 4/5 AEs have been seen. Related AEs seen in >20% of patients include: rash, mucositis, diarrhea, fatigue, transient visual changes, nausea, edema, neutropenia and vomiting. Antitumour activity was seen at each dose level of binimetinib. Final data on toxicity, response, PK and confirmation of RP2D will be presented at the meeting.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The addition of binimetinib to pemetrexed/carboplatin appears to have manageable toxicity with evidence of activity in non-squamous NSCLC. Dose expansion in genotypically defined cohorts will continue and a cohort combining binimetinib with pembrolizumab is planned.

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-04 - Next Generation Sequencing in Lung Cancer Using the Oncomine Comprehensive Assay: The Canadian Publicly Funded Experience (ID 12181)

      16:45 - 18:00  |  Author(s): Maggie Sawczak

      • Abstract
      • Slides

      Background

      Standard of care (SOC) diagnostics for patients with stage IV non-small cell lung cancer (NSCLC) in Canada includes EGFR and ALK testing. Other genomic alterations are not tested routinely; however, access to enhanced molecular testing may broaden treatment options, clinical trial access, and improve outcomes for patients. This study uses the Oncomine Comprehensive Assay (OCA) v3, a next generation sequencing (NGS) panel in NSCLC to evaluate actionable targets, clinical trial eligibility, treatment impact, costs, turnaround time, and patient preference.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Consecutive consenting stage IV NSCLC outpatients at the Princess Margaret Cancer Centre without EGFR/ALK/KRAS/BRAF derangement diagnosed at the University Health Network (UHN) in Toronto, Canada will be enrolled to undergo OCA testing on diagnostic samples. The selected platform (OCA v3, ThermoFisher) includes 161 genes including hotspots, fusions, and copy number variations. Patient age, pathologic subtype, genotyping results and treatment history will be collected. Primary endpoints include incremental actionable targets identified and clinical trial opportunities (clinicaltrials.gov) added through incremental testing beyond SOC. Secondary endpoints include treatment changes as a result of OCA testing, costs from the perspective of the Canadian public healthcare system, patient willingness-to pay, and test turnaround time.

      4c3880bb027f159e801041b1021e88e8 Result

      The study activated in February 2018 with 7 patients enrolled as of April 2018. Results of the value of incremental OCA testing beyond standard of care in the Canadian public healthcare system will be presented at the meeting.

      8eea62084ca7e541d918e823422bd82e Conclusion

      While OCA testing in patients with advanced NSCLC may identify more actionable targets than selected genotyping, its cost effectiveness in the Canadian healthcare system is unknown and will be determined through this study.

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