Razak, Albiruni R. Abdul, Wang, Hung-Ming, Chang, Jang-Yang, Ahn, Myung-Ju, Munster, Pamela, Blumenschein, George, Solomon, Benjamin, Lim, Darren Wan-Teck, Hong, Ruey-Long, Pfister, David, Saba, Nabil F., Lee, Se-Hoon, Van Herpen, Carla, Quadt, Cornelia, Bootle, Douglas, Blumenstein, Lars, Demanse, David and Delord, Jean-Pierre (2023) A Phase 1b/2 Study of Alpelisib in Combination with Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Targeted oncology. ISSN 1776-260X

Abstract

Alpelisib in combination with cetuximab showed synergistic anti-tumour activity in head and neck squamous cell carcinoma (HNSCC) models.The recommended phase 2 dose (RP2D) was determined in a phase 1b dose-escalation study. Phase 2 evaluated anti-tumour activity with a randomised part in cetuximab-naïve patients and a non-randomised part in cetuximab-resistant patients. Alpelisib was administered in 28 d cycles as whole tablets, suspension from crushed tablets or suspension from dispersible tablets in patients with platinum-resistant, recurrent/metastatic HNSCC.The RP2D determined for alpelisib was 300 mg/d. Alpelisib-cetuximab achieved an overall response rate of 25% and 9.9% and disease control rate of 75% and 43.7% in phase 1b and phase 2 studies, respectively. Median progression-free survival (PFS) per central review was 86 d for combination treatment and 87 d for cetuximab monotherapy (unadjusted HR 1.12; 95% CI 0.69-1.82; P > 0.05). When adjusted for baseline covariates [sum of longest diameters from central data, haemoglobin and white blood cell (WBC), the results favoured combination treatment (adjusted HR 0.54; 95% CI 0.30-0.97; P = 0.039). PFS per investigator assessment resulted in an unadjusted HR of 0.76 (95% CI 0.49-1.19; P > 0.05) favouring combination treatment. The median PFS in cetuximab-resistant patients was 3.9 months.The addition of alpelisib to cetuximab did not demonstrate a PFS benefit in cetuximab-naïve patients with advanced HNSCC. The alpelisib-cetuximab combination showed moderate activity in cetuximab-resistant patients, with a consistent safety profile.ClinicalTrials.gov NCT01602315; EudraCT 2011-006017-34.

Item Type:	Article
Date Deposited:	09 Nov 2023 00:45
Last Modified:	09 Nov 2023 00:45
URI:	https://oak.novartis.com/id/eprint/50928