105PD - TG4010 immunotherapy combined with first-line chemotherapy in advanced non-small cell lung cancer (NSCLC). Phase 2b results of the TIME study

Date 16 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Elisabeth Quoix
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors E. Quoix1, J. Nemunaitis2, Z. Papai3, H. Lena4, D. Genet5, C. Louis6, M. Cobo7, Y. Al Farhat8, B. Marie-Bastien9, J.M. Limacher10
  • 1Pulmonology, Nouvel Hopital Civil, 67091 - Strasbourg/FR
  • 2Oncology, Mary Crowley Cancer Center, Dallas/US
  • 3Pulmonology, Szent György Kórház, Szekesfehervar/HU
  • 4Department Of Pulmonology, CHU de Pontchaillou, 35033 - Rennes/FR
  • 5Arch, Clinique Chenieux, Limoges/FR
  • 6Department Of Oncology, Centre Hospitalier de l'Ardenne, Libramont/BE
  • 7Department Of Pulmonology, Hospital Universitario Virgen de la Victoria, Malaga/ES
  • 8Department Of Oncology, Tolna Megyei Onkormanyzat Balassa Janos Korhaza, Szekszard/HU
  • 9Medical Affairs, Transgene SA, Illkirch/FR
  • 10Medical Affairs, Transgene SA, 67400 - Illkirch/FR

Abstract

Aim/Background

TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1tumor-associated antigen and interleukin-2. Previous Phase 2 trials have demonstrated the safety and efficacy of TG4010 in combination with chemotherapy for the treatment of advanced NSCLC. In addition, a previous study showed that a normal level of Triple Positive Activated Lymphocytes (TrPAL, CD16 + CD56 + CD69+) at baseline might be a predictive biomarker for TG4010 efficacy.

Methods

TIME is a double-blind randomized phase 2b/3 study comparing the combination of first-line chemotherapy with TG4010 or placebo NCT01383148). Phase IIB part objective is to validate the TrPAL biomarker with a Bayesian approach. Primary endpoint is PFS according to RECIST 1.1; secondary objectives are response rate (RR), safety, overall survival (OS) and subgroup analyses.

Results

At the time of this analysis, 221 patients were enrolled out of which 170 had a normal TrPAL level at baseline. The analysis of PFS was conducted after 144 events of progression in this cohort: the hazard ratio (HR) was 0.74 (95% CI:0.53-1.02) which corresponds to a 98.6% Bayesian probability that the true HRis <1, passing the threshold of 95% necessary to meet the efficacy endpoint in patients with normal TrPAL. When looking at the 75% of patients with the lowest baseline level of TrPAL at screening (n = 152) PFS analysis shows a HR of 0.66 (95% CI: 0.46-0.96, p = 0.014). Sub-group analysis in patients with non-squamous tumors show also a statistically significant improvement in PFS when treated with TG4010 (n = 195, HR = 0.71; CI: 0.51-0.97; p = 0.016). In the whole study population RR was 39.1% with TG4010 versus 28.8% with placebo (p = 0.03). OS data will be presented at the time of the meeting. TG4010 was generally well tolerated with TG4010 related adverse events limited to mild or moderate injection site reactions, as reported in 31% of the patients.

Conclusions

These data confirm the efficacy and safety profile of TG4010 in stage IV NSCLC especially in patients with non-squamous tumors and/or a low level of TrPAL at baseline. They support the continuation of the TIME study to the Phase 3 part.

Clinical trial identification NCT01383148

Disclosure

E. Quoix: Investigator and Advisor, Transgene SA.

J. Nemunaitis: Investigator and advisor honorarium.

Z. Papai: Investigator honorarium, Transgene SA.

B. Marie-Bastien: Employee and stock ownership.

J.M. Limacher: Employee and stock ownership, Transgene SA.

All other authors have declared no conflicts of interest.