ASCO Rehash 2016 Brian Boulmay MD LSUHSC New
ASCO Rehash 2016 Brian Boulmay, MD LSUHSC- New Orleans Section of Hematology & Oncology *many slides adapted from ASCO 2016 vitual meeting
Pembrolizumab Plus Chemotherapy as Front. Line Therapy for Advanced NSCLC: KEYNOTE 021 Cohorts A-C Abstract 9016 Gadgeel S, Stevenson J, Langer C, et al.
Background • Standard of care for m. NSCLC without mutation is stil a platinum doublet. ▫ Pembrolizumab has efficacy for previosuly treated NSCLC ▫ The KEYNOTE- 10 trial established an improvement in overall survival when compared to docetaxel. � 12. 7 months v 10. 4 months �For tumors with >=50% PDL 1 expression: � 14. 9 v 8. 2 months ▫ Pembrolizumab is approved for use in the US in the second line after a platinum-based doublet in tumors that express PDL 1 Herbst The Lancet 2016
Study Design • Phase I/II trial of pembro + platinum based doublet first line. • Key Eligibility: ▫ Age 18 -75, any NSCLC histology, EGFR and ALK wild-type, no active CNS mets…. and any PDL 1 status.
Study Schema
Results: Baseline Characteristics
Results: Baseline Characteristics
Safety Signals • Three patients in cohort B stopped study drug due to AEs ▫ Grade III pneumonitis ▫ Grade III drug hypersensitivity ▫ Grade III colitis • No treatment related deaths
Immune-Related AEs
RESULTS: ORR
RESULTS: ORR
PFS Median: 10. 3 months Median: NR Median 10. 2 months
Overall Survival Median: NR
Conclusions • Chemotherapy plus pembrolizumab appears to be well tolerated ▫ Exception is bevacizumab containing regimen • Keynote 189 - evaluating pem/platinum +/pembrolizumab is recruiting for Non-Sq. NSCLC • Keynote 407 - evaluting Taxol/platinum +/pembrolizumb is recruiting for Sq. CCa
Checkmate 032: Nivolumab Alone or in Combination with Ipilimumab for the Treatment of Recurrent Small Cell Lung Cancer Antonia S, et. al. Abstract 100
Small cell lung cancer • Trivial progress in the last three decades • Good responses, recurrence is the rule • Second line therapy basically ineffective
Small cell lung cancer • Small cell lung cancer is generally felt to be a ‘cold tumor’ ▫ T-cell infiltrates are sparse • Unlike melanoma, NSCLC • In theory, immune therapy with PD 1 would not be effective. ▫ No T-cells to activate
Ipilimumab is not active in the tumor environment, but in the lymphoid compartment May enhance T-cell infiltrate of cold tumors
Checkmate 032
Checkmate 032
Checkmate 032 • Tocixity: ▫ 79% had toxicity of any grade in the Nivo 1+Ipi 3 arm. ▫ Diarrhea and fatigue most common ▫ 4% pneumonitis
Checkmate 032
Checkmate 032
Checkmate 032
Conclusions • Safety profile is similar to other diseases. • Durable objective response rates • Tumors responded despite low PDL 1 expression • Nivo 1/Ipi 3 chosen for further study ▫ Checkmate 032 expanded ▫ Checkmate 451 maintenance
Plug • AZ Trial to open at LSU ▫ Durvalumab plus tremelimumab first line NSCLC
- Slides: 26