1472P - Phase II study of carboplatin/etoposide plus LY2510924, a CXCR4 peptide antagonist, versus carboplatin/etoposide in patients with extensive-stage s...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Small Cell Lung Cancer
Therapy
Biological Therapy
Presenter David Spigel
Citation Annals of Oncology (2014) 25 (suppl_4): iv511-iv516. 10.1093/annonc/mdu355
Authors D.R. Spigel1, R.W. Weaver2, M. McCleod3, O. Hamid4, J.R. Stille5, J. Polzer6, S. Roberson5, R. Salgia7
  • 1Lung Cancer Research Program, Sarah Cannon Research Institute, US-37203 - Nashville/US
  • 2Medical Oncology, Florida Cancer Specialists, St. Petersburg/US
  • 3Medical Oncology, Florida Cancer Specialists, Fort Myers/US
  • 4Oncology, Eli Lilly and Company, 46285 - Indianapolis/US
  • 5Chorus, Eli Lilly and Company, Indianapolis/US
  • 6Advanced Analytics - Data Mining, Eli Lilly and Company, 46285 - Indianapolis/US
  • 7Dept. Of Medicine, The University of Chicago Medical Centre, Chicago/US

Abstract

Aim

LY2510924, an antagonist to the chemokine receptor CXCR4, inhibits tumor growth and metastasis in xenograft models. A Phase I trial with LY2510924 demonstrated an acceptable safety profile with a robust pharmacodynamic profile. This open-label phase II trial evaluated the clinical benefit of carboplatin/etoposide plus LY2510924 versus carboplatin/etoposide, the standard of care (SOC), as a first-line therapy in patients (pts) with extensive-stage SCLC.

Methods

Treatment-naïve extensive-stage SCLC pts were randomized 1:1 to receive six 21-day cycles of either LY+SOC (Arm A) or SOC (Arm B). A 20-mg dose of LY2510924 was self-administered by the patient subcutaneously on days 1-7 of each cycle. Efficacy was evaluated using RECIST v. 1.1; adverse events were evaluated using MedDRA v. 14.0. The primary end point, progression-free survival (PFS), was analyzed using a stratified log-rank test. Secondary end points were objective response rate (ORR), duration of overall response (DoR), overall survival (OS), and safety.

Results

Median follow-up time was 8.4 months. Pt characteristics were comparable in Arm A (N=47) and Arm B (N=43). Median PFS for Arm A was 5.88 months (95% confidence interval 4.83, 6.24) and Arm B 5.85 months (4.63, 6.51), p=0.9806. ORRs were 74.5% and 81.0%; median DoR were 4.83 months (3.58, 5.09) and 4.67 months (3.32, 5.78) for Arms A and B, respectively. The median OS was 9.72 months (6.64, 11.70) and 11.14 months (8.25, 13.44), p=0.1120 for Arms A and B, respectively. Grade 3/4 treatment-emergent adverse events>8% in Arm A included neutrophil count decrease (40% vs. 56%), anemia (30% vs. 33%), platelet count decrease (23% vs. 16%), lung infection (11% vs. 0%), white blood cell count decrease (9% vs. 9%), and febrile neutropenia (9% vs. 2%) (Arm A vs. Arm B). No pts died due to adverse events.

Conclusions

No improvements in PFS, ORR, DoR, or OS in treatment-naïve extensive-stage SCLC pts were observed when LY2510924 was added to SOC. The addition of LY2510924 to SOC appeared to increase incidence of lung infection and febrile neutropenia; otherwise, the overall toxicity profile was acceptable in this patient population.

Disclosure

O. Hamid: Oday Hamid is employed by Eli Lilly, the sponsor of the study and owns stock in the company; J.R. Stille: Employee of Eli Lilly and Company; J. Polzer: Employee of Eli Lilly and Company. S. Roberson: Employee of Eli Lilly and Company. All other authors have declared no conflicts of interest.