Introduction: The phase 2 KEYNOTE-C11 study (NCT05008224) evaluates the safety and efficacy of pembrolizumab (pembro) followed by AVD chemotherapy (chemotherapy) and pembro consolidation in patients with untreated, early unfavorable or advanced-stage cHL without radiotherapy. The criteria for study continuation were met at the pre-specified interim futility analysis after pembrolizumab induction and 2 cycles of AVD, with approximately 3 months of follow-up. We present results of an analysis of efficacy and safety in all enrolled patients with an additional 8 months of follow-up.

Methods: Patients aged ≥18 years with newly-diagnosed, early unfavorable or advanced stage cHL, received induction with pembrolizumab 200 mg IV on d1 Q3W for 3 cycles, followed by a PET2 to determine response. All patients then received 2 cycles standard dose AVD on d1 and 15 for 2 cycles (chemotherapy phase 1) followed by PET3. Patients who were PET3-negative (Deauville score 1-3) received 2-4 additional cycles AVD based on bulk. Patients aged ≤60 years who were PET3-positive (Deauville score 4-5) received 2-4 cycles of escalated bleomycin plus etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escBEACOPP, chemotherapy phase 2). All patients then received consolidation pembrolizumab 400 mg Q6W for 4 cycles followed by a PET4 assessment. The primary endpoint for this analysis was investigator assessed PET3-negativity response in all treated patients. A posthoc PET analysis was also performed in the actuarial population of all treated patients who reached PET2 or PET3.

Results: At data cut-off (Apr 5, 2023), the median (range) follow-up was 11.8 months (9.7-17.6). A total of 146 patients with untreated cHL were enrolled. Median (range) age was 34.5 years (18-78); 32 (22%) patients had bulky disease, 84 (57%) and 62 (43%), respectively, had advanced and early unfavorable disease. Of 146 patients, 137 (94%) had completed pembrolizumab monotherapy, 130 of 136 (96%) who proceeded to chemotherapy phase 1 completed chemotherapy phase 1, and 127 of 130 (98%) completed chemotherapy phase 2 (111 [AVD]; 16 [BEACOPP]). The PET2-negativity rate was 29% and 31% in all treated patients (N=146) and the actuarial population (n=137), respectively. The PET3-negativity rate was 70% and 78% in all treated patients (N=146) and the actuarial population (n=131), respectively. The ORR at end of PET2 and PET3 was 78% and 88%, respectively. Grade ≥3 drug related adverse events (AEs) were reported in 23 of 146 (16%) patients who received pembrolizumab alone or at consolidation, 94 of 136 (69%) patients who received AVD, and in 10 of 17 (59%) patients who received escBEACOPP. Immune mediated AEs were reported in 37 (25%) patients who received pembrolizumab alone and consolidation, most commonly hyperthyroidism (10%) and hypothyroidism (6%). There were no deaths due to study drug related or immune-mediated AEs.

Conclusion: Pembrolizumab induction followed by chemotherapy continued to be well tolerated in patients with newly-diagnosed, early unfavorable, or advanced-stage cHL, with 70% achieving a PET3-negative response as assessed by investigator after the initial chemotherapy phase. There were no new safety concerns and study is ongoing.

Advani:Genentech: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; Epizyme: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cyteir: Research Funding; Merck: Research Funding; Gilead: Research Funding; Seagen: Research Funding. Avigdor:Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Travel/Accommodations/Expenses; MSD: Research Funding. Sureda Balari:MSD: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau; Kite: Consultancy, Speakers Bureau. Lavie:MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel/Accommodation expenses, lecture; Medisson: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board and Travel/Accommodation expenses; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Lecture; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Lecture; Roche: Honoraria, Other: Advisory Board. Hohaus:MSD: Research Funding. Zaucha:Medical University of Gdańsk: Current Employment; BMS: Research Funding; Pierre Fabre, Takeda, BMS, Gilead, Novartis, Pfizer, Amgen, F. Hoffmann-La Roche Ltd, Astra Zeneca, Abbvie: Honoraria; MSD: Research Funding. Hua:MSD: Research Funding. Zilioli:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: travel expenses, Speakers Bureau; Incyte: Speakers Bureau; Janssen: Other: travel expenses, Speakers Bureau; Lilly: Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Other: travel expenses. Gazitua:Pfizer: Other: Travel; BMS: Speakers Bureau; Roche: Other: Travel; Non-remunerated activity; MSD: Research Funding. Ozcan:Takeda: Research Funding; Acerta: Research Funding; Pfizer: Research Funding; MSD: Research Funding; Bayer: Research Funding; Janssen: Research Funding; PSI: Research Funding; Roche: Research Funding; Abbvie: Other: Travel/Accommodations/Expenses, Research Funding; Sandoz: Other: Travel/Accommodations/Expenses. Odeleye-Ajakaye:Merck & Co., Inc.: Current Employment, Current equity holder in publicly-traded company. Reddy:Merck & Co., Inc., Rahway, NJ, USA: Current Employment, Current equity holder in publicly-traded company. Marinello:Merck & Co., Inc.: Current Employment, Current equity holder in publicly-traded company. Winter:Merck & Co., Inc., Rahway, NJ, USA: Research Funding.

2023
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