Kedar Kirtane

Background: Treatment‐related symptoms and toxicities are common in Head and Neck Cancer (HNC) patients undergoing chemoradiation (CRT). This underscores the importance of timely interventions and effective symptom and toxicity monitoring strategies to mitigate complications and improve quality of life (QoL). Traditional clinician and care team assessments often underreport patient symptoms, leading to urgent care and emergency room admissions, referred to as health care utilization (HCU). In contrast, electronically captured patient‐reported outcomes (ePROs) are associated with improved survival, better health‐related QoL, and lower HCU. Wearable activity monitors (WAMs) offer an additional method for continuous monitoring, enabling clinicians to detect symptoms and toxicities more efficiently and respond rapidly to patient needs. Methods: 12 HNC patients were assessed with ePROs and WAMs during CRT. Results: HNC patients undergoing CRT are receptive to ePRO and WAM‐based monitoring. Conclusions: HNC patients are receptive to participating in ePROs and WAM studies.

Background: Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing after PD-1/PD-L1 inhibitors have poor outcomes and limited treatment options. In the phase 2 BERIL-1 study, the pan-class I PI3K inhibitor buparlisib combined with paclitaxel improved objective response rates (ORR) and progression-free survival (PFS), supporting further evaluation in the post-immunotherapy setting. Methods: BURAN was an international, open-label, randomized phase 3 trial conducted at 142 centers in 18 countries. Eligible patients with R/M HNSCC and disease progression following PD-1 or PD-L1 inhibitor therapy were randomly assigned (2:1) to receive buparlisib plus paclitaxel or paclitaxel alone. The primary endpoint was overall survival (OS). Secondary endpoints included PFS, ORR, duration of response (DoR), safety and health-related quality of life. Findings: Between April 2021 and November 2023, 487 patients were randomly assigned to receive buparlisib plus paclitaxel (n=323) or paclitaxel alone (n=164). Median OS was 9·6 months with buparlisib plus paclitaxel and 9·7 months with paclitaxel alone (HR 1·02, 95% CI 0·83-1·26; p=0·85). PFS was similar between groups. ORR was numerically higher with buparlisib plus paclitaxel (30·3% vs 20·7%; difference 9·6%, 95% CI 1·3-17·3; nominal p=0·024), although responses were not more durable. Grade ≥3 adverse events occurred more frequently with buparlisib plus paclitaxel than with paclitaxel alone (87·5% vs 59·4%), leading to higher rates of treatment discontinuation. Interpretation: In patients with R/M HNSCC progressing after PD-1/PD-L1 inhibitors, the addition of buparlisib to paclitaxel did not improve survival outcomes despite increasing response rates. The lack of durable clinical benefit and increased toxicity do not support the use of buparlisib plus paclitaxel in an unselected population in this setting.

Supplementary Figure 8. Study design for Part A and Part D.

Supplementary Table 4. Cellular markers used for ex vivo immune phenotyping.

Peptide list and HLA types from T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study

Supplementary Figure 3. Patient responses to individual neoantigens at pre-treatment and post-treatment for patients who received mRNA-4157 monotherapy (A–C) or combination therapy (D–J) using ELISpot assay.

Supplementary Table 1. Representativeness of study participants.

Supplementary Figure 2. Characterization of mRNA-4157 neoantigen pool-specific T cells post-expansion at pre-treatment and post-treatment for patients who received mRNA-4157 monotherapy (A–C) or combination therapy (D–K). (L) Alluvial plot illustrating neoantigen reactivity.

Supplementary Figure 6. mRNA-4157 in combination with pembrolizumab activates an adaptive immune response.