Virtual Library

Start Your Search

A. Steino



Author of

  • +

    P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      P2.01-084 - Post-Market Clinical Trial of Dianhydrogalactitol in the Treatment of Relapsed or Refractory Non-Small Cell Lung Cancer (ID 998)

      09:30 - 09:30  |  Author(s): A. Steino

      • Abstract
      • Slides

      Background:
      The median overall survival time for patients with stage IV non-small cell lung cancer (NSCLC) is 4 months, and 1- and 5-year survival is less than 16% and 2%, respectively. NSCLC is usually treated with surgery followed by radiation and treatment with platinum-based regimens or in some cases Tyrosine Kinase Inhibitors (TKIs). Unfortunately, long-term prognosis with platinum-based therapies is poor, and TKI resistance has emerged as a significant unmet medical need. Dianhydrogalactitol (VAL-083) is a structurally unique bi-functional alkylating agent mediating interstrand DNA crosslinks at N[7] of guanine. It has previously demonstrated activity against NSCLC in NCI-sponsored preclinical and clinical trials and is approved for treatment of lung cancer in China (Approval No. Guoyao Zhunzi H45021133); however, it is currently not widely known or used for the treatment of NSCLC.

      Methods:
      not applicable

      Results:
      Recent preclinical data suggest that VAL-083 may be a therapeutic option for drug-resistant NSCLC. VAL-083 has superior activity to cisplatin in both in vitro and in vivo models of NSCLC, including TKI-resistant NSCLC. When combined with either cisplatin or oxaliplatin in vitro, VAL-083 demonstrates significant superadditivity (p<0.05) and synergism (CI < 1) for both combinations in NSCLC cell lines A549, H1975 and H460. When tested in a standard syngeneic mouse fibrosarcoma model (RIF-1 cell-line in C3H mice), VAL-083 (10 mg/kg) was superior to cisplatin (4 mg/kg) in tumor growth delay. Mice were treated with a single IP injection of either cisplatin, VAL-083 or VAL-083 followed immediately by cisplatin. Combination treatment of with cisplatin produced a more than additive effect by delaying growth 8.65 days. In another in vivo model using NSCLC cell-line A549 in Rag2mice, VAL-083 was given as part of a combination treatment with cisplatin. Tumour growth delays of 11, 18 and 25 days were observed for 2 mg/kg cisplatin in combination with 2, 2.5 or 3 mg/kg VAL-083, respectively, while no significant tumour growth delay was observed between untreated and Cisplatin (2 mg/kg). The median survival time was increased by 2 days for cisplatin alone, while the combination of VAL-083 (2 mg/kg, 2.5 mg/kg and 3 mg/kg) with cisplatin (2 mg/kg) increased survival by 17 days, 17 days, and 14 days, respectively.

      Conclusion:
      The preclinical data strongly suggest VAL-083 as a potential treatment for drug-resistant NSCLC. A planned open-label phase IV (post market) clinical trial will investigate the activity of VAL-083 in relapsed or refractory NSCLC assessed by objective response rates, complete and partial response rates and stable disease. VAL-083 will be dosed in accordance with the approved label (40 mg/day) and the results will provide guidance to treating physicians under the context of VAL-083’s current approval in China, as well as serve as proof of concept for expanded development in the rest of the world.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.