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TG4010 immunotherapy combined with first-line therapy in advanced non-small cell lung cancer (NSCLC): phase IIb results of the TIME study
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  1. Elisabeth Quoix1,
  2. Lecia Sequist2,
  3. John Nemunaitis3,
  4. Thaddeus Beck4,
  5. Piotr Jaskiewicz5,
  6. Jean-Philippe Oster6,
  7. Arnaud Scherpereel7,
  8. Erzsébet Juhász8,
  9. Zsuzsanna Mark9,
  10. Rosa Alvarez10,
  11. Saiama Waqar11,
  12. Joseph Potz12,
  13. Nandagopal Vrindavanam13,
  14. Anton Melnyk14,
  15. Helen Ross15 and
  16. Jean-Marc Limacher16
  1. Aff1 grid.412220.7000000012177138XCHRU strasbourg Strasbourg France
  2. Aff2 grid.32224.350000000403869924Massachusetts General Hospital Cambridge MA USA
  3. Aff3 grid.416487.80000000404554449Mary Crowley Medical Research Center Dallas TX USA
  4. Aff4 grid.492660.f0000 0004 0633 1919Highlands Oncology Group Fayetteville AR USA
  5. Aff5 grid.418165.f0000000405402543Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw Warsaw Poland
  6. Aff6 grid.477063.10000000405941141Centre Hospitalier de Colmar Colmar France
  7. Aff7 grid.410463.40000000404718845CHRU de Lille Hopital Calmette Lille France
  8. Aff8 grid.419688.a0000000404428063Orszagos Koranyi TBC es Pulmonologiai Intezet Budapest Hungary
  9. Aff9 Tudogyogyintezet Torokbalint Torokbalint Hungary
  10. Aff10 grid.410526.40000000102777938Hospital Gregorio Marañon Madrid Spain
  11. Aff11 grid.4367.60000000123557002Washington University St. Louis WA USA
  12. Aff12 Abington Hematology Oncology Associates Inc Willow Grove PA USA
  13. Aff13 Signal Point Clinical Research Center Middletown OH USA
  14. Aff14 grid.477898.d0000 0004 0428 2340Texas Oncology, P.A. - Abilene (South) Abilene TX USA
  15. Aff15 grid.417468.80000000088756339Mayo Clinic Arizona Phoenix AZ USA
  16. Aff16 grid.420228.e0000 0004 0638 2273Transgene S.A., Illkirch Graffenstaden France

https://doi.org/10.1186/2051-1426-2-S3-O12

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    Meeting abstracts

    Background

    TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1 tumor-associated antigen and interleukin-2. A previous study showed that a normal baseline level of Triple Positive Activated Lymphocytes (TrPAL, CD16+CD56+CD69+) might be a predictive biomarker for TG4010 efficacy in advanced NSCLC [1]. TIME is a double-blind Phase IIb/III study comparing the combination of first-line therapy with TG4010 or placebo (NCT01383148).

    Patients and methods

    Primary endpoint of the Phase IIb part of the study was to compare progression-free survival (PFS, according to RECIST 1.1) between TG4010 and placebo arms using a Bayesian design, in stage IV NSCLC patients whose tumor express MUC1. Secondary objectives were response rate, safety, survival and subgroup analyses according to stratification factors and level of TrPAL at baseline. A dynamic minimization procedure was applied at randomization for histology, prescription of Bevacizumab, type of chemotherapy, performance status and center.

    Results

    217 patients have been enrolled out of which 170 patients with a normal TrPAL level (pre-determined threshold) and an analysis of PFS was conducted in this cohort after 137 events of progression were recorded. The hazard ratio (HR) for PFS is 0.76 (95%CI: 0.54-1.06). This corresponds to a 97.5% Bayesian probability that the true HR is <1, passing the threshold of 95% needed to consider the endpoint met in patients with normal TrPAL. TG4010 related adverse events were limited to mild or moderate fever and injection site reaction. Analysis in the 75% of patients with the lowest baseline level of TrPAL (three lowest quartiles, n = 152) shows a HR for PFS of 0.72 (95%CI: 0.50-1.03) consistent with the observation made in the previous study. Additional pre-planned analyses by subgroup show that patients with non-squamous tumors had a statistically significant improvement in PFS when treated with TG4010 (n = 145, HR = 0.67; CI: 0.46-0.97; p = 0.016) and especially when belonging to the three lowest quartiles (n = 131, HR = 0.63; 95% CI: 0.42-0.93, p = 0.009). Overall survival data will be presented at the time of the meeting.

    Conclusion

    These data confirm TG4010 efficacy and safety profile in stage IV NSCLC especially in patients with low level of TrPAL before treatment. They warrant the continuation of the TIME study with its Phase III part.

    References

    1. 1.↵
      1. Quoix E, et al
      . Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced NSCLC: a controlled phase 2B trial. The Lancet Oncol. 2011;12:1125–33. doi:10.1016/S1470-2045(11)70259-5
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