LBA32 - Imprime PGG, a novel immune modulator, in the 1st-line treatment of stage IV NSCLC: results from a randomized, controlled, multicenter phase 2 study

Date 28 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Walburga Engel-Riedel
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors W. Engel-Riedel1, F. Schneller2, M. Wolf3, W. Schuette4, J. Lowe5, P. Mattson5, M. Gargano5, M.L. Patchen5, R.D. Huhn5, A. Braun5
  • 1Thoraxchirurgische U. Pneumologische Klinik, Krankenhaus Merheim, 55109 - Koln/DE
  • 2Medical Clinic, Rechts der Isar Hospital,TUM, 81675 - Munich/DE
  • 3Dept. Of Hemato/oncology, Klinikum Kassel, DE-34125 - Kassel/DE
  • 4Clinic For Internal Medicine Ii, Hospital Martha-Maria, Halle Dölau, 06120 - Halle/Saale/DE
  • 5Pharmaceutical Group, Biothera, Inc., 55121 - Eagan/US

 

Abstract

Aim

In a recent phase 2 trial of patients (pts) with stage IV NSCLC, Imprime PGG (PGG) in combination with carboplatin/paclitaxel chemotherapy (C/P) and an EGFR-targeted antibody (cetuximab) significantly increased objective response rates (ORR) compared to C/P + cetuximab alone (Schneller F et al, J Thorac Oncol 2014; Vol 9 [Suppl 14], S40). This identically designed phase 2 trial evaluated PGG in combination with C/P and bevacizumab (Bev). The trial was sponsored by Biothera, ClinicalTrials.gov NCT 00874107, EudraCT 2008-006780-37.

Methods

92 pts with stage IV NSCLC were randomized 2:1 to receive PGG (4 mg/kg IV days 1, 8, 15 of each 3-week cycle) + C/P + Bev versus C/P + Bev alone. C/P was administered for 4 to 6 cycles; Bev + PGG were administered until disease progression or intolerable toxicity. Primary endpoint was ORR. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Imaging assessments (CT of chest and abdomen every 6 weeks) were reviewed centrally. The primary analysis included data up to 21 Mar 2014, the prespecified time point at which all pts had either progressed or had the opportunity to complete at least 18 treatment cycles.

Results

An objective response was achieved by 29 out of 48 evaluable pts (60.4%; 1 CR, 28 PR) in the PGG group and 10 out of 23 (43.5%; 0 CR, 10 PR) in the Ctrl group (p = 0.21). Median (m) DoR was 10.3 mos with PGG compared to 5.6 mos with Ctrl. The mPFS was 11.9 mos versus 10.2 mos (HR = 0.84; p = 0.54), and mOS 16.1 mos versus 11.6 mos (HR = 0.66; p = 0.13) among subjects receiving PGG versus Ctrl, respectively. Overall, the incidence of adverse events (AEs) was similar across treatment groups. The most common AEs (occurring in ≥ 5 pts) deemed possibly or probably related to PGG by the investigator were chills (13.6%); dyspnea, fatigue (10.2% each); nausea, pyrexia, and infusion-related reactions (8.5% each). Overall, 37.3% of pts receiving PGG and 43.3% receiving Ctrl discontinued the study due to AEs.

Conclusions

The addition of PGG to C/P + Bev therapy resulted in numerically increased ORR, DoR, PFS and OS, although these results did not reach statistical significance.

Disclosure

J. Lowe, P. Mattson, M. Gargano, M.L. Patchen, R.D. Huhn and A. Braun: The author is an employee of Biothera and has stock options and/or grants.All other authors have declared no conflicts of interest.