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U. Banerji



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    P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P1.08-011 - Clinical Outcome and Prognostic Factors for Advanced Malignant Mesothelioma (MM) Patients (pts) Treated on Phase I Trials (ID 2595)

      09:30 - 17:00  |  Author(s): U. Banerji

      • Abstract
      • Slides

      Background:
      Relapse after approved anticancer treatments is inevitable in MM pts. Novel agents in phase I trials may benefit such pts and the development of a prognostic score can help identify those who are likely to benefit most. We review the outcome of pts with relapsed MM who have participated in phase I trials in the drug development unit (DDU) of the Royal Marsden Hospital (RMH).

      Methods:
      The RMH prognostic score (RPS) (albumin < 35 g/L, lactate dehydrogenase [LDH] > upper limit of normal [ULN], and > 2 sites of metastases) is an objective tool used to select pts for phase I trials. In view of the pattern of disease spread in MM, we sought to define a MM-specific RPS (m-RPS), by assessing baseline patient factors. Data from consecutive patients who participated in 33 phase I trials between 09/2003 and 12/2014 were included in this analysis. The endpoints were time to progression (TTP) overall survival (OS) and safety. Kaplan-Meier analysis using a log rank test was used to determine survival outcomes.

      Results:
      Data from 54 pts, M:F (36:18), median age 62 years (range, 25-76) were studied. All pts had ECOG PS 0-1. TTP was 2.5 (95% CI 1.7-3) months, OS was 7.6 (95% CI 5.3-8.4) months and the clinical benefit rate was 15%; Three (6%) pts had RECIST confirmed partial response (to PI3K pathway inhibitors [n=2] and immunotherapy [n=1]); 5 (9%) pts had RECIST stable disease ³6 months. Male gender was highlighted as a factor of poor prognosis (p=0.004) in a multivariate analysis and therefore, we propose m-RPS for MM pts that now incorporates gender instead of the number of metastatic sites (Table). The good prognosis group [A] (m-RPS 0-1; n=23) had a median OS of 13.7 (95% CI 7.9-24) months and the poor prognosis group [B] (m-RPS 2-3; n=28) had a median OS of 4 (95% CI 2.8-7.5) months, p<0.001. 13 pts (24%) had an OS < 12 weeks: 3 (11%) pts from Group [A] and 10 (36%) pts from Group [B]. 39 (72%) pts experienced G1-G2 toxicities, ³G3 toxicities were seen in 8 (15%) pts and 7 (13%) pts discontinued trial due to toxicity.

      Variable Score
      LDH
      ≤Upper limit of normal (ULN) 0
      >ULN 1
      Albumin
      ³35g/L 0
      <35g/L 1
      Gender
      Female 0
      Male 1
      Table. modified RMH prognostic score (m-RPS)


      Conclusion:
      Experimental agents in the phase 1 setting appeared to be well tolerated with preliminary signals of benefit in selected advanced MM pts. The m-RPS should be prospectively validated as a screening tool for MM pts considered for phase I studies

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    P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P2.08-008 - A Phase 1 Dose Escalation Study of VS-5584, a PI3K/MTOR Inhibitor, Administered with VS-6063, a Focal Adhesion Kinase Inhibitor, in Mesothelioma (ID 2812)

      09:30 - 17:00  |  Author(s): U. Banerji

      • Abstract

      Background:
      Malignant mesothelioma is a rare, but aggressive pleural or peritoneal tumor which is highly invasive and progresses rapidly. The median survival of patients with mesothelioma is between 9 and 13 months, and survival has not been significantly affected by most currently available therapeutic interventions. There are no approved therapies following first line treatment. VS-6063 is an oral inhibitor of focal adhesion kinase (FAK) currently being evaluated in a randomized phase 2 study in patients with malignant pleural mesothelioma who have stable disease or better after front line chemotherapy. VS-5584 is an oral dual inhibitor of PI3K/mTOR currently undergoing phase I testing in solid tumors. Previously reported literature has shown that dual PI3K/mTOR inhibitors have activity in patients with relapsed mesothelioma. In preclinical models, the combination of VS-6063 and VS-5584 have demonstrated synergy in tumor models of malignant mesothelioma supporting the potential exploration of this combination clinically.

      Methods:
      This is a multi-center, open-label, phase 1 trial in subjects with relapsed malignant mesothelioma. The study is comprised of two sequential parts: Part 1 (Dose Escalation of VS-5584 with a fixed dose of VS-6063) and Part 2 (Expansion). Patients receive VS-5584 orally on an intermittent dosing schedule and VS-6063 400 mg orally BID. Primary endpoints are to determine the maximum tolerated dose, recommended Phase 2 dose/schedule and to assess safety and tolerability of the combination in this patient population. Secondary endpoints include assessing the pharmacokinetics of VS-5584 and VS-6063 when co-administered. Exploratory endpoints include response rate and biomarker correlation with response and PD. The study is currently enrolling across 4 sites in the United States and United Kingdom. Clinical trial: NCT02372227.

      Results:
      Not applicable

      Conclusion:
      Not applicable