2378P - Efficacy and safety outcomes with pembrolizumab (pembro) rechallenge for patients (pts) with advanced/metastatic urothelial cancer (UC) who responded to first-course treatment

Background

Pembro has shown durable antitumor activity in advanced/metastatic UC across multiple studies. Rechallenging pts who previously responded to pembro and had their disease subsequently progress may be a potential treatment strategy. We conducted a post hoc pooled analysis of outcomes of pembro rechallenge in pts from the phase 3 KEYNOTE-045 (NCT02256436), phase II KEYNOTE-052 (NCT02335424), and phase 3 KEYNOTE-361 (NCT02853305) studies.

Methods

Pts were included in the pooled analysis if they received pembro monotherapy in the course of one of the studies and stopped pembro after CR or had CR, PR, or SD to first-course pembro and completed 2 y of treatment. Protocol-specified pembro rechallenge was administered at a dose of 200 mg Q3W for up to 17 cycles (∼1 y). Outcomes in this exploratory analysis included ORR, DOR, PFS, OS, and safety of second-course pembro.

Results

A total of 49 pts were included (n = 11, KEYNOTE-045; n = 10, KEYNOTE-052; and n = 28, KEYNOTE-361). Best overall response to first-course pembro included 21 CRs, 23 PRs, 3 SDs, and 2 non-CRs/non-PDs (defined as persistence of ≥1 nontarget lesions and/or maintenance of tumor marker level above the normal limits). Median duration of the first response to pembro was 26.7 mo (range, 4.1-54.9+). Median time between first and second course was 10.7 mo (range, 1.0-36.3); median duration of second course was 8.3 mo (0.0-13.2). Seventeen pts (35%) completed second-course pembro; the most common reason for discontinuation was disease progression (n = 19; 39%). ORR to second-course pembro was 41% (8 CR; 12 PR) and median DOR was 14.0 mo (2.1+ to 20.5). From start of second-course treatment, the 12-mo PFS rate was 45% and the 24-mo OS rate was 61%. Treatment-related adverse events (AEs) occurred in 22 pts (45%); 3 pts (6%) experienced grade 3-4 treatment-related AEs. Three pts (6%) discontinued due to a treatment-related AE, and no pts died due to a treatment-related AE.

Conclusions

Consistent with prior reports, pts with advanced/metastatic UC whose disease had prior response to pembro may benefit from pembro rechallenge. The safety profile of pembro rechallenge was consistent with the known safety profile of pembro monotherapy.

Clinical trial identification

KEYNOTE-361: NCT02853305; Release date: August 2, 2016. KEYNOTE-045: NCT02256436; Release date: October 3, 2014. KEYNOTE-052: NCT02335424; Release date: January 9, 2015.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Shane Walton, PhD and Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

V.S. Koshkin: Financial Interests, Personal, Advisory Board: Janssen, Clovis, Astellas, AstraZeneca, Pfizer, EMD Serono; Financial Interests, Personal, Other, Consulting: GLG, ExpertConnect, Guidepoint; Financial Interests, Institutional, Local PI: Merck, Taiho, Eli Lilly, Clovis, Novartis; Financial Interests, Institutional, Steering Committee Member: Seagen; Financial Interests, Personal and Institutional, Research Grant: Prostate Cancer Foundation. P. Danchaivijitr: Financial Interests, Personal and Institutional, Invited Speaker: MSD, Roche, AstraZeneca, BMS; Financial Interests, Personal and Institutional, Speaker’s Bureau: MSD, Roche, AstraZeneca, BMS; Financial Interests, Personal and Institutional, Advisory Board: MSD, Roche, AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: MSD, Roche, AstraZeneca. Y. Su: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Ipsen, Merck Serono, Ono, Roche, TTY Biopharm Company, Merck; Financial Interests, Personal, Principal Investigator: Janssen, Merck Serono, Roche, Merck; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck Serono, Merck; Financial Interests, Personal, Research Grant: Ono; Financial Interests, Personal, Funding: Ono. J.A. Arranz Arija: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Eisai, Merck, MSD, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Institutional, Advisory Board: SOGUG. M. Boegemann: Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Principal Investigator: MSD; Financial Interests, Personal and Institutional, Advisory Role: MSD. S.P. Neciosup Delgado: Other, Personal, Member: ASCO, ESMO; Financial Interests, Personal, Principal Investigator: MSD, BMS, Roche, Novartis, Daiichi. S. Cheng: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca. E. Rosenbaum: Financial Interests, Personal, Advisory Board: Novartis, Janssen, BMS, Pfizer; Financial Interests, Personal and Institutional, Advisory Board: MSD, Astellas, Bayer; Financial Interests, Personal and Institutional, Principal Investigator: MSD, Astellas, Bayer; Financial Interests, Personal and Institutional, Funding: Bayer. K. Lopez: Non-Financial Interests, Personal, Principal Investigator: Oncomedica; Non-Financial Interests, Institutional, Full or part-time Employment: Hospital General San Juan de Dios. A. Bavle: Non-Financial Interests, Personal and Institutional, Stocks/Shares: Merck; Non-Financial Interests, Personal and Institutional, Sponsor/Funding: Merck. C. Liu: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Full or part-time Employment: Merck. K. Imai: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks or ownership: Merck. A. Furka: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: MSD, AstraZeneca, WNT Research, Pfizer; Financial Interests, Personal, Invited Speaker: KRKA; Financial Interests, Personal, Advisory Board: KRKA. All other authors have declared no conflicts of interest.