Background
Only a minority of patients (20%) with Human Papillomavirus (HPV) 16-positive recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) responds to first-line (1L) monotherapy with pembrolizumab, and no approved therapies exist targeting HPV+ disease specifically. Eseba-vec (previously known as HB-200) utilizes arenavirus vectors to induce potent HPV-16 E6 and E7-specific CD8 T-cell responses. Previously, we reported compelling clinical activity of eseba-vec alone and in combination with pembrolizumab as 1L treatment for patients with HPV16+ PD-L1 combined positive score (CPS) ≥20 R/M HNSCC. Here, we report further updated results in 1L patients with CPS ≥20.
Methods
Participants received intravenous eseba-vec (every 3 weeks [Q3W] for the first 5 doses, then Q6W for the sixth dose and onward) in combination with pembrolizumab (200 mg Q3W or 400 mg Q6W). Two dose levels were explored. Safety, T-cell response, and preliminary clinical activity were assessed.
Results
As of 5 August 2024, 60 patients with HPV16+ PD-L1+ R/M HNSCC (58 with oropharyngeal cancer) were treated with eseba-vec plus pembrolizumab in the 1L setting. Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 26/60 (43.3%) patients, serious TEAEs in 14/60 (23.3%) patients. There were 4/60 (6.7%) patients with TEAEs leading to treatment discontinuation, and 3 treatment emergent death cases (two unrelated and one related in a patient receiving additional chemotherapy as a protocol deviation). 30/60 patients exhibit PD-L1 CPS ≥20. Baseline characteristics for these 30 patients: median age 69 (range 38–76), male 26 (86.7%), White 28 (93.3%), with smoking history 15 (50%), 28 (93.3%) received prior chemoradiation and 29 (96.7%) naïve to checkpoint inhibitor (CPI). 21/30 patients are evaluable (≥1 post-baseline tumor scan) with at least 18 weeks follow-up after first dose, the overall response rate per RECIST v1.1 was 52.4% (4 complete response, one confirmed after data cut-off; 6 partial response, and 1 unconfirmed response) and disease control rate was 85.7%. 60% of the confirmed responders were ongoing at data cut-off. Progression-free survival and overall survival data are still maturing and will be presented.
Conclusions
Eseba-vec plus pembrolizumab continue to demonstrate an overall favorable combination safety profile and promising clinical activity in the PD-L1 CPS ≥20 population as 1L treatment in patients with HPV16+ R/M HNSCC. AVALON-1, a phase 2/3 randomized pivotal study has been initiated in this patient population. Clinical trial# NCT04180215
Trial Registration
ClinicalTrials.gov NCT04180215.
Ethics Approval
This study was approved by Ethics and Institutional Review Boards (IRBs) at all study sites. 20-165A(5) (Memorial Sloan Kettering Cancer Center), 1282128 (University of Alabama at Birmingham Heersink School of Medicine), 1273311 (University of Kansas Medical Center), IRB22-1121 (Cleveland Clinic), 202101073 (University of Iowa), 1266389 (Banner MD Anderson Cancer Center), STUDY-19-01049 (Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute), HS-19-00931 (University of Southern California, Norris Cancer Center), ‘BUA-2023-034-001’ (University of California Los Angeles), H-200-001 (RM 662) (Stephenson Cancer Center at University of Oklahoma Health Sciences Center), 1346811 (University of Virginia Health System), IRB19-1294 (University of Chicago), PRO00036737 (Medical College of Wisconsin), i21-00729 (Grossman School of Medicine), EC/21/252/6495 ( R) (Hospital Virgen del Rocio), 1353073 (Rutgers Cancer Institute of New Jersey) All participants provided written informed consent.