LBA37 - Active8: A randomized, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with motolimod immunotherapy in patient...

Date 07 October 2016
Event ESMO 2016 Congress
Session Immunotherapy of cancer
Topics Anti-Cancer Agents & Biologic Therapy
Cancer Immunology and Immunotherapy
Head and Neck Cancers
Presenter Ezra Cohen
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors E. Cohen1, N.F. Saba2, B. Gitlitz3, R. Haddad4, A. Sukari5, P. Neupane6, J.C. Morris7, K. Misiukiewicz8, K.L. Manjarrez9, G.N. Dietsch10, J.K. Bryan9, R.M. Hershberg11, R.L. Ferris12
  • 1Translational Science, UCSD Moores Cancer Center, 92093 - La Jolla/US
  • 2Head And Neck Oncology, Emory University Winship Cancer Institute, 30322 - Atlanta/US
  • 3Oncology, Keck School of Medicine, University of Southern California, Los Angeles/US
  • 4Head And Neck Oncology Program , Dana-Farber Cancer Institute, 02215 - Boston/US
  • 5Oncology, Karmanos Cancer Institute, Detroit/US
  • 6Medical Oncology, University of Kansas Cancer Center, Kansas City/US
  • 7Comprehensive Lung Cancer Center, University of Cincinnati Cancer Institute, Cincinnati/US
  • 8Hematology-oncology, Mount Sinai Medical Center, New York/US
  • 9Clinical, VentiRx Pharmaceuticals, 98101 - Seattle/US
  • 10Research And Development, VentiRx Pharmaceuticals, 98101 - Seattle/US
  • 11Ceo, VentiRx Pharmaceuticals, 98101 - Seattle/US
  • 12Division Of Head And Neck Surgery Departments Of Otolaryngology, University of Pittsburgh Cancer Institute, 15213 - Pittsburgh/US



Patients (pts) with recurrent or metastatic SCCHN have poor outcomes despite therapy with the EXTREME regimen (platinum, 5-FU, cetuximab [CTX]). The Toll-like receptor 8 agonist motolimod (M) stimulates the innate immune system, increasing antigen-specific T cell responses against EGFR. In SCCHN pts, M + CTX enhanced NK cell activity, decreased markers of T cell suppression, and reduced myeloid-derived suppressor cells in tumors, with most pts having a characteristic motolimod injection site reaction (ISR). A randomized phase 2 study tested whether M can improve clinical outcomes in SCCHN when combined with EXTREME.


Pts were randomized 1:1 to EXTREME + motolimod (M) (N = 100) or EXTREME + placebo (N = 95) and stratified by ECOG 0 vs. 1, prior systemic therapy for SCCHN, and choice of cisplatin or carboplatin. The primary endpoint was progression-free survival (PFS) per independent central review. Key secondary endpoints included overall survival (OS) and safety.


Median age was 58 yrs (range, 23–81), ECOG was 0 (38%) or 1 (62%), and 65% of pts had previously received systemic treatment for SCCHN. The majority of pts (80%) were assigned to receive carboplatin at baseline. In the intent-to-treat (ITT) population, the median PFS for EXTREME + M was 185 vs. 181 days for control (HR 0.99, P = 0.266). Median OS in the ITT population was 412 vs. 343 days for EXTREME + M vs. control, respectively (HR 0.95, P = 0.399). A subgroup analysis examining EXTREME + M pts experiencing an ISR showed significant improvements in PFS (216 vs. 181 days, HR 0.69, P = 0.005) and in OS (570 vs. 382 days, HR 0.56, P = 0.015) vs. controls. Adverse events with increased incidence in the EXTREME + M arm included ISR, pyrexia, chills, anemia, influenza-like illness, and dermatitis acneiform.


Adding M to EXTREME did not improve PFS or OS in the ITT population, though significant benefits were observed in a subgroup with immune-related ISR. EXTREME + M was generally well tolerated, with no unexpected adverse events or serious adverse events, and no evidence of synergistic toxicities.

Clinical trial identification Identifier: NCT01836029. Release date: April 12, 2013.

Legal entity responsible for the study

VentiRx Pharmaceuticals, Inc.


VentiRx Pharmaceuticals, Inc.


E. Cohen: Stock ownership: HLI Advisory boards: BMS, AZ, Pfizer, Merck, Merck Serono, Aspyrian, GenMab. N.F. Saba: Advisory boards: Merck, Pfizer, BMS. R. Haddad: Advisory boards: BMS, Merck, AstraZeneca, Pfizer, Celgene Research grants: BMS, Merck, AstraZeneca, Celgene Consultant: BMS, Merck, AstraZeneca, Pfizer. J.C. Morris: Speaker bureau: Boehringer-Ingelheim. K.L. Manjarrez, G.N. Dietsch: Employee of VentiRx Pharmaceuticals with equity ownership in the company and patents related to motolimod (VTX-2337). J.K. Bryan: I am an employee of VentiRx Pharmaceuticals and have equity ownership in the company. R.M. Hershberg: Employment: VentiRx Pharmaceuticals, Celgene Corp Stock ownership: VentiRx, Celgene Corp Patent: Motolimod (VTX-2337) Board of Directors: VentiRx, Nanostring, Adaptive Biotechnologies Consultant: Frazier Healthcare. R.L. Ferris: Advisory boards: Merck, Celgene, Bristol Myers Squibb, AZ/Medimmune Research grants: VentiRx, Bristol Myers Squibb, AZ/Medimmune. All other authors have declared no conflicts of interest.