Slide 1: Ficerafusp alfa (2000 mg Q2W) and pembrolizumab in HPV-negative first-line R/M HNSCC
Ficerafusp alfa (2000 mg Q2W) and pembrolizumab in HPV-negative first-line recurrent/metastatic head and neck squamous cell carcinoma Dan P. Zandberg, John M. Kaczmar, Assuntina G. Sacco, Glenn J. Hanna, Christine H. Chung, Jennifer Choe, Eric Sherman, Tamara A. Sussman, Catherine Shu, Jonathan Haym
Slide 2: Disclosure
Disclosure Dan P. Zandberg • Consulting or advisory role: Bicara Therapeutics Inc., Blueprint Medicines, Coherus Biosciences, InhibRx, Macrogenics, Merck & Co., Inc., Rahway NJ, USA, Prelude Therapeutics, Seagen • Research funding: Aduro Biotech, AstraZeneca, AVEO, Bicara Therapeutics Inc., Bristol
Slide 3: Objectives
Objectives Upon completion of this activity, attendees will be able to: • Describe ficerafusp alfa’s unique mechanism of action: dual targeting of TGF-β and EGFR in HPV-negative HNSCC • Explain how TGF-β neutralization remodels the fibrotic TME to enable tumor penetration that drives deep and durabl
Slide 4: Background and unmet need in HNSCC
Background and unmet need in HNSCC HPV-negative R/M HNSCC with CPS ≥1 is characterized by poor clinical outcomes1-4 Pembrolizumab + Pembrolizumab Chemotherapy Failing to distinguish HPV status in Any HPV status KEYNOTE-0481 tumors can mask important ORR 19% 36% efficacy and prognostic signals 2,5 mD
Slide 5: HPV-negative R/M HNSCC: overexpression of EGFR and TGF-β
HPV-negative R/M HNSCC: a challenging tumor type associated with overexpression of EGFR and TGF-β Overexpression of EGFR and TGF-β in HNSCC1 6 HPV-negative HNSCC has distinct 40,000 biological and mutational features that affect prognosis2-4 Log2(EGFR_FKPM+1) Serum TGF-β1 (pg/mL) 4 30,000 • Increase
Slide 6: Ficerafusp Alfa: A bifunctional TGF-β ligand-trapping x EGFR-directed antibody
Ficerafusp Alfa A bifunctional TGF-β ligand-trapping x EGFR-directed antibody 1,2 TGF-β trapping combined with EGFR targeting remodels the fibrotic TME, enhances tumor penetration of immune cells, and may synergize with 2 Targeting EGFR ICIs for deep, durable 1. Direct antitumor effect responses 2.
Slide 7: High response rates observed across doses with ficerafusp alfa + pembrolizumab
High response rates observed across doses with ficerafusp alfa + pembrolizumab in HPV-negative, CPS ≥1, 1L R/M HNSCC ESMO Asia 2025 ASCO 2025 • Deep and durable responses with 750 mg QW† 1500 mg QW ‡ 750 mg and 1500 mg suggest EE set (N=30) EE set (N=28) long-term efficacy Confirmed ORR 57% (17/30)
Slide 8: Ficerafusp alfa Phase 1b dose-expansion cohorts
Ficerafusp alfa Phase 1b dose-expansion cohorts: HPV-negative, CPS ≥1, 1L R/M HNSCC Dose expansion Ficerafusp alfa’s half-life of ~ 8 days supports the Ficerafusp alfa + pembrolizumab rationale to explore less frequent dosing schedules Ficerafusp alfa 1500 mg QW + Pembrolizumab 200 mg Q3W Today’s fo
Slide 9: Patient characteristics with ficerafusp alfa 2000 mg Q2W
Patient characteristics with ficerafusp alfa 2000 mg Q2W + pembrolizumab in HPV-negative, CPS ≥1,1L R/M HNSCC Characteristic Safety set (N=30) Age, years Median (range) 63 (28-84) Sex Male/female 67%/33% Oropharynx 20% Population (HPV negative) • 1L R/M HNSCC Primary site of disease Oral cavity 63%
Slide 10: Safety with ficerafusp alfa 2000 mg Q2W
Safety with ficerafusp alfa 2000 mg Q2W + pembrolizumab in HPV-negative CPS ≥1, 1L R/M HNSCC Most frequently reported TEAEs related to ficerafusp alfa (≥20%)* Safety set (N=30) Any grade Grade 3† Any TEAE 29 (97%) 16 (53%) • The combination was tolerable with a Dermatitis acneiform 24 (80%) 3 (10%)
Slide 11: Efficacy with ficerafusp alfa 2000 mg Q2W + pembrolizumab
Efficacy with ficerafusp alfa 2000 mg Q2W + pembrolizumab in HPV-negative, CPS ≥1,1L R/M HNSCC EE set (N=27) CPS 1-19 100 PD CPS ≥20 Confirmed ORR 48% (13/27) 80 Disease control rate 85% (23/27) 60 Deep response* 77% (10/13) Best change from baseline (%) 40 PD PD PD CR rate 26% (7/27) 20 Median time
Slide 12: Efficacy with ficerafusp alfa 2000 mg Q2W + pembrolizumab (subgroups)
Efficacy with ficerafusp alfa 2000 mg Q2W + pembrolizumab in HPV-negative, CPS ≥1,1L R/M HNSCC EE set (N=27) CPS 1-19 100 PD CPS ≥20 Confirmed ORR 48% (13/27) 80 Disease control rate 85% (23/27) 60 Deep response* 77% (10/13) Best change from baseline (%) 40 PD PD PD CR rate 26% (7/27) 20 Median time
Slide 13: Sustained TGF-β neutralization and tumor penetration of T-cells
Sustained TGF- neutralization and tumor penetration of T-cells with ficerafusp alfa 2000mg Q2W + pembrolizumab TGF- Neutralization (plasma) CD8+ T-Cells (paired biopsies) Q2W2000 Patient with Complete Response CD8+ Baseline Week 3 25 ** CD8 AVG Positive Area 20 15 10 Patient with -58% tumor reduct
Slide 14: Consistency efficacy of ficerafusp alfa + pembrolizumab across doses
Consistency efficacy of ficerafusp alfa + pembrolizumab in HPV-negative, CPS ≥1,1L R/M HNSCC Ficerafusp alfa dose 750 mg QW* 1500 mg QW† 2000 mg Q2W EE set (N=30) EE set (N=28) EE set (N=27) Confirmed ORR 57% (17/30) 54% (15/28) 48% (13/27) • High response rates CPS 1-19 73% (8/11) 54% (7/13) 57% (8
Slide 15: Ficerafusp alfa 2000 mg Q2W: summary
Ficerafusp alfa 2000 mg Q2W + pembrolizumab in HPV-negative, CPS ≥1, 1L R/M HNSCC: summary • Efficacy and safety consistent with 1500mg QW, including deep responses • Deep responses: 77% of responders had ≥80% tumor shrinkage • 26% had a CR • Rapid responses: median 1.6 months • Consistent safety pr
Slide 16: FORTIFI-HN01 study
FORTIFI-HN01 study: Global, multicenter, randomized, double-blind, phase 2/3 study of ficerafusp alfa or placebo in combination with pembrolizumab for 1L treatment of PD-L1-positive, R/M HNSCC Dose decision (selected) Arm A Ficera 1500 mg QW Population (N~650) + pembro Q3W • 1L R/M HPV-negative HNSC
Slide 17: Acknowledgements
Acknowledgements Patients who participated in the study and their families and caregivers Investigators and clinical trials support staff: UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA; UC San
Slide 18: Thank you
MULTIDISCIPLINARY m n Cc S HEAD AND NECK CANCERS SYMPOSIUM ADVANCING PATIENT-CENTERED CARE THROUGH INNOVATIVE TEAM SCIENCE fF 'T SPRINGS | PALM DESERT, CA | FEBRUARY 19 - 21, 2026