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M.A. Socinski



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    OA 14 - New Paradigms in Clinical Trials (ID 681)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      OA 14.07 - Progress in Lung Squamous Cell Carcinoma from the Lung-MAP Master Protocol (S1400) Sub-Studies S1400A, S1400B, S1400C and S1400D (ID 9593)

      11:00 - 12:30  |  Author(s): M.A. Socinski

      • Abstract
      • Presentation
      • Slides

      Background:
      Lung-MAP (S1400) is a master umbrella protocol designed to establish genomic screening for previously treated squamous cell lung cancer patients (SqCCA), and independently evaluate targeted therapies with matching biomarkers and alternative therapies (designated non-match therapy) in patients without putative markers. The protocol opened June 16, 2014 with four biomarker-driven sub-studies and one non-match sub-study.

      Method:
      Eligibility stipulated advanced SqCCA, progressing after at least one prior platinum-based chemotherapy, PS 0–2, and EGFR/ALK wild-type. Tumor samples were required and analyzed for gene alterations by FoundationOne NGS assay (Foundation Medicine). The original biomarker and non-match studies were: S1400B evaluating taselisib for PI3K mutations, S1400C evaluating palbociclib for cell cycle gene alterations (CCGA), S1400D evaluating AZD4547 for FGFR mutations, S1400E evaluating rilotumumab and erlotinib for c-MET positive tumors, and S1400A evaluating durvalumab in patients with no matching biomarkers. The original design included randomization to a control arm, but was amended to a single-arm phase 2 design. The primary endpoint for each modified sub-study was response.

      Result:
      As of June 16, 2017 all original sub-studies have been closed to accrual; 1298 patients registered to the screening component of the trial and 486 patients have registered to a sub-study. Two new sub-studies have been launched and are currently accruing. Details of the completed sub-studies are included in the table.

      Sub-study Final Accrual Biomarker prevalence/% of sub-study registrations Closure Date Response to investigational therapy N (%) Status
      S1400A (non-match) Total: 116 Durvalumab: 78 Docetaxel: 38 NA/59% 12/18/15 Docetaxel arm closed: 4/22/15 11 (16%) Administratively closed to enable activation of new non-match study.
      S1400B PI3K Total: 39 taselisib: 31 Docetaxel: 8 8%/9% 12/12/16 Docetaxel arm closed: 12/18/15 1 (4%) Closed at interim futility analysis.
      S1400C (CCGA+) Total: 54 Palbociclib: 37 Docetaxel: 17 19%/15% 09/01/16 Docetaxel arm closed: 12/18/15 2 (6%) Closed at interim futility analysis.
      S1400D (FGFR+) Total: 45 AZD4547: 35 Docetaxel: 10 16%/12% 10/31/16 Docetaxel arm closed: 12/18/15 2 (7%) Closed at interim futility analysis.
      S1400E (MET+) Total: 9 R+E: 4 E: 5 N/A (closed too early) 11/26/2014 N/A Closed d/t discontinuation of development of rilotumumab


      Conclusion:
      Lung-MAP as a master genomic screening protocol has demonstrated feasibility with respect to accrual and evaluation of targeted therapies in lower prevalence patient populations. This dynamic, centralized, single-IRB platform is well positioned to efficiently assess multiple novel therapeutics for advanced SqCCA patients.

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    P3.08 - Locally Advanced Nsclc (ID 724)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P3.08-004 - Phase I/II Trial of Nab-Paclitaxel or Paclitaxel Plus Carboplatin with Concurrent Radiation for Inoperable Stage IIIA/B NSCLC (ID 10220)

      09:30 - 16:00  |  Author(s): M.A. Socinski

      • Abstract
      • Slides

      Background:
      To determine the overall survival of Nab-Paclitaxel (Nab) or Paclitaxel (P) plus Carboplatin (C) with concurrent radiation therapy (RT) followed by consolidative chemotherapy (CT) with Nab-C or PC for patients (pts) with Stage IIIA/B Non-small cell lung cancer (NSCLC) when compared to historical controls and to assess for the safety of each regimen to guide further investigation

      Method:
      This phase I/II trial randomized 98 pts (6 pts phase I; 92 pts phase II). 75 pts were eligible for analysis on the phase II portion. For the phase I portion, weekly 50mg/m[2] of Nab and C AUC 2 was administered with concurrent thoracic RT (60-66 Gy) followed by CT comprising 100mg/m[2] Nab on days 1,8,15 (of a 21 day cycle) and C AUC 6 on day 1 for 2 cycles. For the randomized phase II portion, patients received either arm A) weekly 50mg/m[2] P and C AUC 2 or arm B) weekly 40mg/m[2] of Nab and C AUC 2 with concurrent RT followed by consolidative 200mg/m[2] P and C AUC 6 every three weeks for 2 cycles or 100mg/m[2] Nab on days 1,8,15 (of a 21 day cycle) and C AUC 6 on day 1 for 2 cycles. The primary end point was 2-year overall survival of 50% or greater.

      Result:
      Median follow up was 14.3 months. 2 patients experienced dose-limiting toxicities on the phase I portion as defined per protocol (grade 3 febrile neutropenia and grade 4 thrombocytopenia) leading to a dose reduction of concurrent Nab from 50mg/m[2 ]to 40mg/m[2] for the phase II portion. On the Phase II portion, Grade 3+ esophagitis was 3 and 2 pts, Grade 3+ pneumonitis was 3 and 5 pts and Grade 4+ hematological adverse events was 3 and 8 pts on A and B arms respectively. The 1- and 2-year overall survival rates for arm A and B were 80.6% (95%CI 63.4-90.3) and 69.2% (51.2-81.7); and 72.5% (48.4-86.8) and 56.5% (33.7-74.1) respectively. The 1- and 2-year progression free survival were 57.5% (38.7-72.5) and 46.1% (29.2-61.5); and 45.5% (24.7-64.3) and 20.7% (6.5-40.3) for arm A and B respectively.

      Conclusion:
      For pts with locally advanced Stage IIIA/B NSCLC, both arms A and B provided 2-year overall survival rates greater than 50%. The addition of Nab to chemoradiation was overall well tolerated, prompting potential interest going forward. Further analyses of quality of life measurements are currently underway. This project was supported by Celgene. Clinical Trial information: NCT01757288

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