Abstract 432P
Background
Pembro provided durable benefit and manageable safety in patients (pts) with previously treated MSI-H/dMMR mCRC in the phase II KEYNOTE-164 study (NCT02460198; data cutoff, Sept 4, 2018). Pembro is approved as 1L therapy for unresectable or metastatic MSI-H/dMMR CRC and for disease that has progressed after fluoropyrimidine, oxaliplatin, and irinotecan. Final analysis of KEYNOTE-164 with ∼29.5 mo of additional follow-up is shown.
Methods
Pts were ≥18 y with locally advanced unresectable or metastatic MSI-H/dMMR CRC and prior therapy (cohort A: fluoropyrimidine, oxaliplatin, and irinotecan; cohort B: ≥1 line of SOC—fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan ± anti-VEGF/EGFR antibody). Pts received pembro 200 mg IV Q3W for ≤35 cycles or until disease progression, unacceptable toxicity, or withdrawal. Pts who stopped pembro and then had PD could receive a 2nd course of pembro (≤17 cycles). Primary end point was ORR per RECIST v1.1 by central review. Secondary end points were DOR, DCR, and PFS per RECIST v1.1; OS; and safety.
Results
Median (range) time from first dose to data cutoff (Feb 19, 2021) was 62.2 mo (60.8-65.2) in cohort A and 54.4 mo (52.7-56.7) in cohort B. ORR was 33% in cohort A and 35% in cohort B; median OS was 31.4 mo (95% CI, 21.4-58.0) and 47.0 mo (19.2-NR), respectively (Table). OS in pt subgroups by response and prior line of therapy will be presented. TRAEs occurred in 64% of pts in cohort A and 71% in cohort B; grades 3/4 TRAEs in 16% and 13%, respectively. No grade 5 TRAEs occurred. Immune-mediated AEs and infusion reactions occurred in 21% of pts in cohort A and 38% in cohort B. 9 pts received a 2nd course of pembro: 5/6 in cohort A and 1/3 in cohort B had second-course PR. Table: 432P
| Cohort A (n = 61) | Cohort B (n = 63) | |
| ORR,a n | 20 | 22 |
| ORR,a % (95% CI) | 33 (21-46) | 35 (23-48) |
| Best overall response | ||
| CR,a n (%) | 3 (5) | 9 (14) |
| PR,a n (%) | 17 (28) | 13 (21) |
| DOR,a median (range), mo | NR (6.2-58.5+) | NR (4.4-52.4+) |
| PFS,a median (95% CI), mo | 2.3 (2.1-8.1) | 4.1 (2.1-18.9) |
| 36-mo PFS rate, % | 29 | 34 |
| OS, median (95% CI), mo | 31.4 (21.4-58.0) | 47.0 (19.2-NR) |
| 48-mo OS rate, % | 40 | 49 |
| Pts with a PFSa event, n | 44 | 40 |
| OS in pts with a PFSa event, median (95% CI), mo | 20.5 (9.5-27.8) | 17.3 (8.1-28.6) |
| 48-mo OS rate in pts with a PFSa event, % | 15 | 19 |
aPer RECIST v1.1 by independent review committee. NR, not reached. + indicates no progressive disease at last assessment.
Conclusions
Pembro continued to show durable clinical benefit, remarkable OS, and manageable safety in pts with previously treated MSI-H/dMMR mCRC.
Clinical trial identification
NCT02460198.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Jemimah Walker, PhD, and Doyel Mitra, PhD, CMPP, of ApotheCom (Yardley, PA, USA).
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
D.T. Le: Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Advisory Role: Merck, BMS; Financial Interests, Personal, Research Grant: Merck, BMS, Aduro, Medivir, Curegenix, Nouscom; Financial Interests, Personal, Royalties, Licensing; Patent: Self. L. Diaz: Financial Interests, Personal, Advisory Role: Merck, Caris, Lyndra, Genocea Biociences, Illumina, Cell Design Labs, Neophore; Financial Interests, Personal, Leadership Role: PGDx; Financial Interests, Personal, Stocks/Shares: PGDx, Thrive, Neophore; Financial Interests, Personal, Other, Travel Expenses: Merck; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Royalties: Multiple, managed by Johns Hopkins and MSKCC COI; Financial Interests, Personal, Member of the Board of Directors: Personal Genome Diagnostics (PGDx), Jounce Therapeutics. T.W. Kim: Financial Interests, Institutional, Research Grant: Sanofi, AstraZeneca. E. Van Cutsem: Financial Interests, Personal, Advisory Role: Array, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex, Taiho; Financial Interests, Personal, Funding: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier paid to his institution. R. Geva: Financial Interests, Personal, Other, Honoraria: BMS, Lilly, Medison, Roche, Novartis, Janssen, Takeda, MSD,Pfizer, MERCK; Financial Interests, Personal, Advisory Role: EISAI, Astrazeneca, Bayer, MSD, Novartis, BI. BOL Pharma, Roche; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Travel Expenses: Merck, Bayer, BMS, Medison; Financial Interests, Personal, Stocks/Shares: BOL; Financial Interests, Personal, Project Lead: Pyxis; Financial Interests, Personal, Stocks/Shares: Pyris. D. Jäger: Financial Interests, Personal, Advisory Role: MSD, Roche, BMS, Biontech, Bayer. H. Hara: Financial Interests, Personal, Other, Honoraria: Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, Merck Biopharma, MSD, Ono, Sanofi, Taiho, Takeda, Yakult; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayel, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Elevar Therapeutics, GSK, Incyte, Merck Biopharma, MSD, Ono, Pfizer, Taiho; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo, Lilly, MSD, Ono. M. Burge: Financial Interests, Personal, Advisory Role: BMS. B. O'Neil: Financial Interests, Personal, Advisory Role: Array, Astellas, Astrazeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex, Taiho. P. Kavan: Financial Interests, Institutional, Funding: Merck Canada; Financial Interests, Personal, Speaker’s Bureau, Expert Testimony: Merck Canada; Financial Interests, Personal, Advisory Role: Merck Canada. T. Yoshino: Financial Interests, Personal, Other, Honoraria: Taiho, Chugai, Eli Lilly, Merc Biopharma, Bayer, Ono; Financial Interests, Personal, Research Grant: Taiho, Sumitomo Dainippon, Ono, Chugai, Amgen, Parexel International, MSD, Daiichi Snakyo, Sanofi. R. Guimbaud: Financial Interests, Personal, Advisory Role: AAA; Financial Interests, Personal, Speaker’s Bureau, Expert Testimony: Amgen, AstraZeneca, Servier, MSD, Pierre Fabre, Ipsen. E. Elez: Financial Interests, Personal, Other, Honoraria: Amgen; Array Biopharma; Bayer; Bristol Myers Squibb; Hoffman La-Roche; Merck Serono; Sanofi; Servier; Financial Interests, Personal, Advisory Role: Amgen; Array Biopharma; Bayer; Bristol Myers Squibb; Hoffman La-Roche; Merck Serono; Sanofi; Servier; Financial Interests, Institutional, Research Grant: AbbVie; Amgen; Array Pharmaceuticals; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; GlaxoSmithKline; Hoffman La-Roche; Medimmune; Merck Serono; MSD; Novartis; Pierre-Fabre; Sanofi Adventis. S. Al-Batran: Financial Interests, Personal, Invited Speaker: AIO Studien; Bristol Myers Squibb; Lilly; MCI Deutschland; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Immutep; Lilly; MacroGenics; Merck Sharp & Dohme; Other, Personal, Leadership Role: Institute of Clinical Cancer Research, IKF at Northwest Hospital; Financial Interests, Institutional, Research Grant: AstraZeneca; Bristol Myers Squibb; Celgene; Eurozyto; Federal Ministry of Education and Research; German Cancer Aid (Krebshilfe); German Research Foundation; Hospira; Immutep; Ipsen; Lilly; Medac; Merck Sharp & Dohme; Roche; Sanofi; Vifor. P. Boland: Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Other: Ipsen; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Personal, Other: Macrogenics. Y. Cui: Financial Interests, Personal and Institutional, Full or part-time Employment: MSD China. P. Leconte: Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal and Institutional, Full or part-time Employment: MSD France. P. Marinello: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.. T. André: Financial Interests, Personal, Other: Amgen; AstraZeneca; Bristol Myers Squibb; Chugai; GlaxoSmithKline; Merck Sharp & Dohme Corp; Pierre Fabre; Roche/Vantana; Sanofi; Servier; Financial Interests, Personal, Advisory Board: Amgen; Bristol Myers Squibb; Clovis Oncology; Gritstone Oncology; Halliodx; Merck Sharp & Dohme Corp; Pierre Fabre; Roche/Vantana; Seagen; Sanofi; Servier; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Merck Sharp & Dohme Corp; Servier; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme Corp; Bristol Myers Squibb; Financial Interests, Personal, Other: Roche/Vantana; Merck Sharp & Dohme Corp; Bristol Myers Squibb; Non-Financial Interests, Personal, Other: Scientific committee of ARCAD foundation and GERCOR group. All other authors have declared no conflicts of interest.