Brian Boulmay, MD LSUHSC- New Orleans Section of Hematology & Oncology ASCO Rehash 2016 Brian Boulmay, MD LSUHSC- New Orleans Section of Hematology & Oncology *many slides adapted from ASCO2016 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 mNSCLC 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% PDL1 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 PDL1 Herbst The Lancet 2016

Phase I/II trial of pembro + platinum based doublet first line. 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 PDL1 status.

Study Schema

Results: Baseline Characteristics

Results: Baseline Characteristics

Three patients in cohort B stopped study drug due to AEs 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 10.2 months Median: 10.3 months Median: NR

Overall Survival Median: NR Median: NR Median: NR

Chemotherapy plus pembrolizumab appears to be well tolerated Conclusions Chemotherapy plus pembrolizumab appears to be well tolerated Exception is bevacizumab containing regimen Keynote 189- evaluating pem/platinum +/- pembrolizumab is recruiting for Non-SqNSCLC Keynote 407- evaluting Taxol/platinum +/- pembrolizumb is recruiting for SqCCa

Antonia S, et. al. Abstract 100 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 PD1 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 Nivo1+Ipi3 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 PDL1 expression Nivo1/Ipi3 chosen for further study Checkmate 032 expanded Checkmate 451 maintenance

Plug AZ Trial to open at LSU Durvalumab plus tremelimumab first line NSCLC