90PD - Previously treated advanced NSCLC cohort from a multi-disease phase 1 study of ramucirumab (R) plus pembrolizumab (P): Efficacy and safety data

Date 07 May 2017
Event ELCC 2017
Session Targeted therapies and immunotherapies
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Roy Herbst
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors R.S. Herbst1, J. Martin-Liberal2, E. Calvo3, N. Isambert4, J. Bendell5, P. Cassier6, J. Jin7, G. Mi8, J. Rege7, L. Paz-Ares9
  • 1Medical Oncology, Yale University School of Medicine, 06520 - New Haven/US
  • 2Vall d'Hebron University Hospital, Barcelona/ES
  • 3Early Clinical Drug Development Program, START Madrid-HM CIOCC, Centro Integral Oncológico Clara Campal, Madrid/ES
  • 4Centre Georges-François Leclerc (Dijon), Dijon/FR
  • 5Sarah Cannon Research Institute/Tennessee Oncology, Nashville/US
  • 6Centre Léon Bérard and Claude Bernard University, Lyon/FR
  • 7Eli Lilly and Company, Bridgewater/US
  • 8Eli Lilly and Company, Indianapolis/US
  • 9Virgen del Rocio University Hospital, Sevilla/ES

Abstract

Background

R (anti-VEGFR2) and P (anti-PD-1) are active in previously treated advanced NSCLC. Median progression-free survival (PFS) reported in KEYNOTE-001 (previously treated; PD-L1 all comers) was 3.0 months (95%CI, 2.2-4.0) and ORR was 18%. This is the first study to combine R with P.

Methods

Ongoing, multi-cohort, phase 1a/b trial enrolled pts with confirmed NSCLC with prior progression on systemic therapy, measurable disease, ECOG PS 0-1 and baseline tumor tissue. PD-L1 was classified strongly positive (tumor proportion score [TPS] ≥50%), weakly positive (TPS=1-49%), or negative (TPS <1%) using the DAKO PD-L1 22C3 IHC pharmDx assay. Primary objective- assess safety and tolerability of R + P; preliminary efficacy will be examined.

Results

As of 21-Nov-2016, 27 pts with previously treated advanced NSCLC received R at 10 mg/kg on Day 1 with P 200 mg on Day 1 q3W. Median age was 65, 78% male, 96% had a history of smoking, 78% had adenocarcinoma and 15% had squamous-cell carcinoma. Sixteen (59%) pts received ≥2 and 4 (15%) received ≥3 prior treatment regimens for their disease. Median duration of treatment was 7.0 mo (IQR 3.0-12.4) and 8.3 mo (IQR 3.3-12.4) for R and P, respectively. Treatment related adverse events (TRAEs) occurred in 25 (93%) pts, most commonly hypertension (26%) and asthenia (19%). Five (19%) pts experienced grade 3 TRAEs (adrenal insufficiency, delirium, hypertension [n = 2], hyponatremia, infusion related reaction, proteinuria, and respiratory failure). No grade 4-5 TRAEs occurred. ORR was 30% with a median time to response of 2.1 mo. Duration of response has not been reached. Responses occurred in PD-L1 unknown (n = 1), negative (n = 2), and strong positive (n = 5) groups as well as both histologies. Median PFS was 9.7 mo (95% CI 4.6-11.5) and overall survival rate at 6 mo was 84.9%. Disease control rate was 85%. Ten (37%) pts remain on study treatment, including all responders.

Conclusions

R + P demonstrated encouraging antitumor activity independent of PD-L1 and histology. The safety profile was consistent with monotherapy treatment for each drug, with no additive toxicities. The study was amended and is now enrolling pts with treatment naïve advanced NSCLC.

Clinical trial identification

NCT02443324 JVDF

Legal entity responsible for the study

Eli Lilly and Company, Indianapolis, IN

Funding

Eli Lilly and Company, Indianapolis, IN

Disclosure

R.S. Herbst: Personal fees from Eli Lilly, outside the submitted work. E. Calvo: Institutional research funding: multiple- available upon request; Travel expenses: Lilly, PsiOxus, Novartis; Consultant: Novartis, GSK, Astellas, Genentech, Lilly, Nanobiotich, Pfizer; SB: Novartis. N. Isambert: Honoraria: Pfizer, Novartis; Consulting/Advisory: Merck Serono. J. Bendell: Institutional research funding: From multiple and available upon request, including Lilly and Merck. P. Cassier: Personal fees from Roche/Genentech, Novartis, Astra-Zeneca, Amgen, Plexxikon; non-financial support from Roche/Genentech, Merck Sharp Dohme, Astra-Zeneca, Plexxikon; and grants from Merck Sharp Dohme and Astra-Zeneca, outside the submitted work. J. Jin, G. Mi, J. Rege: Employee and stock holder at Eli Lilly and Company. L. Paz-Ares: Consultant/Advisory role: Roche, Lilly, Novartis, MSD, BMS, Amgen, Clovis, AZ, BI, Pfizer. All other authors have declared no conflicts of interest.