Phase 2 KEYNOTE‐B68 study: pembrolizumab every 6 weeks in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) or primary mediastinal B‐cell lymphoma (PMBCL)
Makaleler > Tam Makale · 2023
Yazarlar: A. McDonald, E. Verburgh, M. Gotti, A. Pinto, J. Zaucha, V. Ivanov, V. Melnichenko, H. Mocikova, M. Ozcan, C. Patti, J. Farias, I. Goncalves, O. Kuchkova, J. Mayer, Güray SAYDAM, S. Tomassetti, K. Pathiraja, K. Ryland, S. Chakraborty, W. Jurczak
Hematological Oncology, Uluslararası, Wos, 2023, cilt 41, ss 575-577
DOI: 10.1002/hon.3164_431
Özet
Introduction: Pembrolizumab (pembro) was originally approved by the FDA for the treatment of R/R cHL and R/R PMBCL at 200 mg every 3 weeks (Q3W). Recently, the FDA granted accelerated approval for pembro 400 mg Q6W in all approved indications based on data from solid tumors. The open-label, single-arm, phase 2 KEYNOTE-B68 study (NCT04875195) is evaluating the efficacy and safety of pembro 400 mg Q6W in patients (pts) with R/R cHL or R/R PMBCL. Results after 9 months of follow-up are presented. Methods: Pts were ≥18 y old, had histologically confirmed cHL or PMBCL, measurable disease per Lugano criteria, an ECOG PS of 0 or 1, and no prior anti–PD-1 therapy. Pts with cHL must have either relapsed during their last regimen for cHL or within 12 months after completing their last regimen, or had relapsed after or failed to respond to ≥1 prior line of multiagent therapy or autologous stem cell transplant (ASCT). Pts with PMBCL must have relapsed after or failed to respond to ASCT, or if ineligible for ASCT, must have relapsed after or failed to respond to ≥2 prior lines of therapy including rituximab. All pts received pembro 400 mg Q6W for ≤18 cycles or until progressive disease (PD), unacceptable toxicity, or withdrawal. The primary end point was ORR per Lugano criteria by investigator review. Secondary end points were DOR and safety. PFS and OS were exploratory. Results: At data cutoff (Oct 18, 2022), 66 pts had been enrolled (R/R cHL, n = 60; R/R PMBCL, n = 6). Median follow-up was 8.9 mo (range, 1–15.9) for pts with R/R cHL and 10.6 mo (range, 5.1–15.4) for R/R PMBCL. ORR was 65% (95% CI, 51.6–76.9; 20 CR/19 PR) for pts with R/R cHL and 50% (95% CI, 11.8–88.2; 2 CR/1 PR) for R/R PMBCL. Median DOR was NR (range, 0.0+ to 8.6+) for pts with R/R cHL and 9.7 mo (range, 2.6–9.7) for R/R PMBCL. Additional efficacy data are summarized in the table. Treatment-related AEs occurred in 24 pts (40%) with R/R cHL and 2 (33.3%) with R/R PMBCL; grade ≥3 treatment-related AEs occurred in 3 pts (5%) and 1 pt (16.7%), respectively. No grade 5 treatment-related AEs occurred. Immune-mediated AEs were reported in 13 pts (21.7%) with R/R cHL and 1 pt (16.7%) with R/R PMBCL; 2 pts (3.3%) with R/R cHL had grade ≥3 immune-mediated AEs (1 grade 3 infusion reaction; 1 grade 3 severe skin reaction). Conclusions: With approximately 9 mo of follow-up, pembro 400 mg Q6W had robust antitumor activity in pts with R/R cHL and R/R PMBCL, with ORR similar to that with pembro 200 mg Q3W. No new safety signals were reported. These results support the use of pembro 400 mg Q6W in hematologic indications. Encore Abstract - previously submitted to ASCO 2023 The research was funded by: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Keywords: Aggressive B-cell non-Hodgkin lymphoma, Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. A. McDonald Employment or leadership position: Alberts Cellular Therapy (Private practice) Consultant or advisory role: Netcare Pty(Ltd), Netcare Pretoria East Hospital Stock ownership: Netcare Pty(Ltd), Netcare Pretoria East Hospital Research funding: Abbvie, Janssen, Merck, Novartis, Astra-Zeneca Educational grants: Abbvie, Janssen, Amgen Other remuneration: Astra-Zeneca, Takeda, Janssen E. Verburgh Consultant or advisory role: MSD, NovoNordisk, Takeda Research funding: MSD Other remuneration: Takeda A. Pinto Consultant or advisory role: Servier, Roche/Genentech, Merck Honoraria: Roche/Genentech, Merck Sharp & Dohme, Servier, Incyte, BMS-Celgene Other remuneration: Incyte-Italy, F. Hoffmann-La Roche AG J. Zaucha Consultant or advisory role: Takeda, BMS, Gilead, Novartis, Pfizer, Amgen Honoraria: Pierre Fabre Research funding: BMS Educational grants: Roche, AbbVie, Takeda V. Ivanov Research funding: Abbvie, MSD, Takeda, Astra Zeneka, Biockad, Astellas, Pfizer M. Ozcan Research funding: AbbVie, Bayer, Janssen, Roche, Takeda, MSD, Pfizer, Acerta Educational grants: AbbVie J. Farias Consultant or advisory role: Roche Other remuneration: AstraZeneca, Roche, Novartis I. Goncalves Consultant or advisory role: Janssen Research funding: Janssen, Takeda, Amgen, Bayer, Novartis, Merck, Bayer, Celgene, Glaxo, Bristol Other remuneration: Janssen J. Mayer Research funding: MSD S. Tomassetti Consultant or advisory role: Curio, Cardinal Health, Rigal Research funding: Natera K. Pathiraja Employment or leadership position: Merck K. Ryland Employment or leadership position: Merck Stock ownership: Merck S. Chakraborty Employment or leadership position: Merck Stock ownership: Merck W. Jurczak Consultant or advisory role: AbbVie, AstraZeneca, BeiGene, Lilly, Roche, Takeda Research funding: AbbVie, AstraZeneca, BeiGene, Janssen, Lilly, Roche, Takeda