A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Status:
Terminated
Trial end date:
2016-09-16
Target enrollment:
Participant gender:
Summary
This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or
metastatic head and neck squamous cell carcinoma (RM HNSCC) patients considered to be
resistant, ineligible or intolerant to platinum-based chemotherapy. The Phase Ib included
three arms. Three different methods of administration and two different BYL719 formulations
were studied to determine the MTD and/or RP2D of BYL719 in combination with cetuximab:
Arm A - film-coated whole tablets were orally administered to patients who were able to
swallow the tablets; Arm B - a drinkable suspension prepared from crushed film-coated tablets
was administered orally to patients with swallowing dysfunction Arm C - a suspension from a
dispersible tablet administered via G-tube, in patients with swallowing dysfunction. Arm C
was used to investigate the pharmacokinetics (PK), compared to Arm A (film coated tablet),
and safety of the dispersible tablet of the dispersible tablet formulation of BYL719.
The Phase II investigated the clinical efficacy of BYL719 and consisted of an open label,
randomized Phase II part investigating BYL719 in combination with cetuximab compared to
cetuximab alone in patients resistant or intolerant to platinum and naïve to cetuximab
(Scheme 1: Arm 1 and Arm 2), and a non-randomized Phase II part Scheme 2: Arm 3. In addition,
patients who experienced disease progression in Arm 2 (cetuximab) were allowed to switch to
the combination regimen (cross-over, Arm 2B). The safety of the BYL719 in combination with
cetuximab was also further characterized in Arms 1, 2B and 3.
Patients were treated until progression of disease), unacceptable toxicity, or withdrawal of
informed consent, whichever occurred first (except for phase II Arm 2 had the opportunity to
crossover to the combination treatment (Arm 2B). In the follow-up period all patients had to
complete the safety follow-up assessments within 30 days after the last dose of the study
treatment. Patients who did not have disease progression at the time of discontinuation of
study treatment were radiologically followed for disease status until disease progression,
initiation of subsequent anticancer therapies, or death, whichever occurred first. In
addition, all patients enrolled in Phase II were followed for survival.