1055PD - TIME, a phase 2b/3 study evaluating TG4010 in combination with first line therapy in advanced non small cell lung cancer (NSCLC). Phase 2b results

Date 28 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Elisabeth Quoix
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors E. Quoix1, G. Losonczy2, F. Forget3, C. Chouaid4, Z. Papai5, R. Gervais6, C.H.H. Ottensmeier7, A. Szczesna8, A. Kazarnowicz9, J..T. Beck10, V. Westeel11, E. Felip12, D. Debieuvre13, A. Madroszyk14, G. Lacoste15, A. Tavernaro15, B. Bastien15, T. Palanche15, J. Limacher15, H. Lena16
  • 1Pneumologie, HUS, 67091 - Strasbourg/FR
  • 2Department Of Pulmonology, Semmelweis University, Budapest/HU
  • 3Oncology, Centre hospitalier de l'Ardenne, Libramont/BE
  • 4Pneumologie, CHIC, Créteil/FR
  • 5Pulmonology, Fejer Megyei Szent Gyorgy Korhaz, 8000 - Szekesfehervar/HU
  • 6Pneumologie, Centre François Baclesse, Caen/FR
  • 7Cancer Sciences Division, Southampton University Hospitals NHS Trust, Southampton/GB
  • 8Lung Diseases, Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy, Otwock/PL
  • 9Oncology, SP Zespol Gruzlicy i Chorob Pluc w Olsztynie, Olsztyn/PL
  • 10Highlands Oncology Group, Highlands Oncology Group, Fayetteville/US
  • 11Pneumologie, CHU, Besançon/FR
  • 12Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 13Service De Pneumologie, Hopital Emile Muller, 68070 - Mulhouse/FR
  • 14Medical Oncology, Paoli Calmettes, 13009 - Marseille/FR
  • 15Medical Affairs, Transgene, 67405 - Illkirch/FR
  • 16Pneumology, CHU Rennes, Rennes/FR

 

Abstract

Aim

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 NSCLC (Lancet Oncol 2011;12:1125-33). TIME is a double-blind phase 2b/3 study (NCT01383148) comparing the combination of first line therapy with TG4010 or placebo. The Phase 2b part aims at prospectively validating the baseline TrPAL level as a predictive biomarker.

Methods

Primary endpoint of the Phase 2b 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 with a MUC1+ tumor. Secondary objectives were response rate, safety, survival and subgroup analyses. 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.

Conclusions

These data support the predictive value of the TrPAL biomarker. They also confirm TG4010 efficacy and safety profile in stage IV NSCLC patients and warrant the continuation of the TIME study with its Phase 3 part.

Disclosure

E. Quoix: Transgene: joint steering committee member and consultant; C. Chouaid: Consultant for Lilly, GSK, Amgen Advisory board member: Lilly, Roche, AZ, Amgen, Boheringer Ingelheim; Z. Papai: Advisory board member for Transgene; V. Westeel: Advisory board member for Roche, Lilly. Honoraria from Astra Zeneca, Boehringer, Teva; G. Lacoste: Transgene employee. Stockoption ownership; A. Tavernaro: Transgene employee. Stockoption ownership; B. Bastien: Transgene employee. Stockoption ownership; T. Palanche: Transgene employee with Transgene stock options; J. Limacher: Transgene employee. Stock option owner. All other authors have declared no conflicts of interest.