Neoadjuvant pembrolizumab (Pembro) for early stage non-small cell lung cancer (NSCLC): Updated report of a phase I study, MK3475-223.

Author:

Bar Jair1,Urban Damien1,Ofek Efrat2,Ackerstein Aliza3,Redinsky Ilanit4,Golan Nir5,Kamer Iris1,Simansky David5,Onn Amir6,Raskin Stephen4,Shulimzon Tiberiu7,Peled Michael8,Zeitlin Nona5,Halparin Sharon4,Jurkowicz Menucha1,Abukhalil Ramez5,Perelman Marina2,Ben-Nun Alon9

Affiliation:

1. Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel;

2. Department of Pathology, Sheba Medical Center, Ramat Gan, Israel;

3. Chaim Sheba Medical Center, Ramat Gan, Israel;

4. Sheba Medical Center, Ramat Gan, Israel;

5. Thoracic Surgery, Sheba Medical Center, Ramat Gan, Israel;

6. Institute of Pulmonology, Sheba Medical Center, Ramat Gan, Israel;

7. Pulmonology Institute, Sheba Medical Center, Ramat Gan, Israel;

8. Pulmonology Instutite, Sheba Medical Center, Ramat Gan, Israel;

9. Department of Thoracic Surgery, Chaim Sheba Medical Center, Ramat-Gan, Israel;

Abstract

8534 Background: Resected NSCLC clinical stage I or II harbor a 5 year survival of only 30-50%. Immunotherapy might be more effective in low-burden disease. We hypothesized that neo-adjuvant immunotherapy is a feasible, safe and effective treatment (Tx) for early stage NSCLC. Methods: MK3475-223 is an ongoing phase I study of neoadjuvant pembrolizumab in stage I-II NSCLC. All Pembro Txs are 200mg q 3 weeks (wks). Objectives: determine safety; recommended phase 2 dose/schedule; pathological & radiological response. Doses-schedule limiting toxicities (DLT) were defined as significant surgical complications (bleeding, delayed wound healing, ARDS, prolonged air-leak) or a significant delay of surgery. The doses-schedule escalation cohorts were (i) single pembro dose 3 wk prior to surgery; (ii) 2 pembro doses, 2 wks later surgery; (iii) 2 pembro doses, 1 wk later surgery. Expansion cohort received the doses-schedule of cohort (iii). Percentages of remaining viable tumor in the post-Tx were assessed, 10% or less was considered amajor pathological response (MPR). IHC for pre-Tx PDL1 was done. Efficacy was evaluated for the patients who had received 2 doses of pembrolizumab. Results: No DLT occurred in the dose-schedule escalation cohorts. 10 patients received 2 cycles of neo-adjuvant pembrolizumab. 4 patients achieved a MPR (4/10 who received 2 cycles of pembro; 40%; 95% C.I. 16.7-68.8%). No correlation is seen between the levels of PDL1 pre-Tx and the pathologic response. Size of the tumor and N status was also not in any apparent correlation with MPR (data not shown). Interestingly, all of the MPR cases had a relatively long interval from 1st Tx till surgery. Clinical trial information: NCT02938624. Conclusions: Neo-adjuvant pembro is safe and feasible. A promising sign of efficacy is seen. Achieving MPR might require a longer 1st-Tx-surgery interval. Predictive biomarkers for response might be different from those in advanced disease. Recruitment and correlative studies are ongoing.[Table: see text]

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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