136MO - Efficacy and safety of pembrolizumab (pembro) monotherapy in East Asian patients (pts) with urothelial carcinoma (UC) in KEYNOTE-045 or KEYNOTE-052

Background

Pembro showed durable antitumor activity and manageable safety for treatment of advanced UC in the first-line (1L) setting for cisplatin-ineligible pts (phase 2 KEYNOTE-052 study [NCT02335424]) and second-line (2L) setting for platinum-refractory pts (phase 3 KEYNOTE-045 study [NCT02256436]). This exploratory analysis evaluated if results for East Asian pts are consistent with global results.

Methods

Pts enrolled at sites in Japan, Malaysia, Singapore, South Korea, and Taiwan from KEYNOTE-045 and KEYNOTE-052 were included. Pts in KEYNOTE-045 were randomly assigned 1:1 to receive investigator’s choice of chemotherapy (chemo; paclitaxel [175 mg/m² IV Q3W], docetaxel [75 mg/m² IV Q3W], or vinflunine [320 mg/m² IV Q3W]) or pembro (200 mg IV Q3W up to 2 y). All pts in KEYNOTE-052 received pembro (200 mg IV Q3W up to 2 y). Objective response rate (ORR) per RECIST v1.1 by blinded independent central review, overall survival (OS), and safety are reported. Data cutoffs were October 1, 2020 (KEYNOTE-045), and September 26, 2020 (KEYNOTE-052).

Results

Overall, 113 pts from KEYNOTE-045 (pembro: n = 62; chemo: n = 51) and 20 pts from KEYNOTE-052 were analyzed. Median (range) follow-up was 62.4 mo (59.2-68.6) in KEYNOTE-045 and 57.3 mo (51.4-65.2) in KEYNOTE-052. Efficacy results are displayed in the table. Grade 3-5 treatment-related adverse events (TRAEs) occurred in 10 (16%) and 37 pts (73%) in the pembro and chemo arms in KEYNOTE-045, respectively; 1 pt each in the pembro and chemo arms died from TRAEs. In KEYNOTE-052, 2 pts (10%) had grade 3-5 TRAEs; 1 pt (5%) died from a TRAE.

Conclusions

In this exploratory analysis, pembro appeared to show generally similar antitumor activity and safety between East Asian pts and the global population for both the 1L setting for cisplatin-ineligible pts and 2L setting for platinum-refractory pts. Small sample size may limit the generalizability of the findings Table: 136MO

Clinical trial identification

NCT02256436 (KEYNOTE-045 [October 3, 2014]) and NCT02335424 (KEYNOTE-052 [January 9, 2015]).

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, 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

J. Lee: Financial Interests, Personal, Other, honoraria: Ipsen Korea, BMS Korea, AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role, Advisory/Consultancy: AstraZeneca Korea, Merck; Financial Interests, Personal and Institutional, Stocks/Shares: Merck, Amgen, Myovant Sciences, Johnson & Jonhson; Financial Interests, Institutional, Invited Speaker: Pfizer, Ipsen, BMS, MSD, Merck, Esai, Roche, AstraZeneca, Exelixis, SeaGen. B. Keam: Financial Interests, Personal, Invited Speaker: Merck, MSD Oncology, AstraZeneca, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Cellid, Handok, TrialInformatics, CbsBioscience, ImmunOncia, NeoImmunetech. R. Kanesvaran: Financial Interests, Institutional, Invited Speaker: Astellas, Johnson and Johnson, Ipsen, Amgen, BMS, MSD, Novartis, AstraZaneca, Sanofi; Financial Interests, Institutional, Advisory Board: Johnson and Johnson, Pfizer, Ipsen, Amgen, BMS, MSD, Bayer, AstraZaneca, Ferring; Financial Interests, Institutional, Research Grant: Sanofi, Eisai, Johnson and Johnson; Non-Financial Interests, Personal, Leadership Role, Past President: Singapore Society of Oncology; Non-Financial Interests, Personal, Leadership Role, President: SIOG; Non-Financial Interests, Personal, Leadership Role, Vice Chairman: Singapore Cancer Society; Non-Financial Interests, Personal, Leadership Role, Medical Advisory Board Member: International Kidney Cancer Coalition. C. Lin: Financial Interests, Personal, Other, Travel support: BeiGene, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Novartis, AbbVie, PharmaEngine, Merck KGaA; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Roche. K. Nishimura: Financial Interests, Personal, Other, Honoraria: Merck BioPharma, Astellas, Janssen Pharmaceutical K.K., AstraZeneca Honoraria. M. Kim: Financial Interests, Personal and Institutional, Advisory Role: MSD, Ipsen, Bristol Myers Squibb, Ono Pharmaceutica, Eisai, YuhanSpeaker ; Financial Interests, Institutional, Research Grant: Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge BioTherapeutics, GSK. J. Xu: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Full or part-time Employment: Merck. B. Homet Moreno: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. K. Imai: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Institutional, Full or part-time Employment: Merck. H. Nishiyama: Financial Interests, Personal, Other, Honoraria: Merck BioPharma, Astellas, Janssen Pharmaceutical K.K., AstraZeneca. S.Y. Rha: Financial Interests, Personal and Institutional, Advisory Role, Advisory/Consultancy: MSD, Daichii Sankyo, Merck, Amgen, AstraZeneca, Indivumed, LG Biochem; Financial Interests, Institutional, Speaker’s Bureau: Lilly, MSD, Amgen, Merck; Financial Interests, Personal, Research Grant: MSD, Daichii Sankyo, Merck, Amgen, AstraZeneca, Lilly, BMS, Roche, Sanoti Aventis, Aslan, Beigine, Zymeworks, Merus, Arcus, Gilead. All other authors have declared no conflicts of interest.