Abstract 907P
Background
CCND1 alternation is common in HPV(-) HNSCC patients. In in vitro and animal study, CDK 4/6 inhibitors can increase T cell function and increase HLA expression in tumor microenvironment. We hypothesized that adding CDK4/6 inhibitors can augment the efficacy of anti-PD1 in HNSCC patients.
Methods
It was a single-center, phase I dose-escalation study with expansion cohort (NCT04213404). The eligibility criteria were: 1) HNSCC patients with recurrent/metastatic diseases; 2) p16(-) in oropharyngeal cancer patients; 3) ECOG 0-1; 4) acceptable organ function; 5) can swallow a whole tablet. The starting dose level was: Spartalizumab (S) 400mg iv Q4wk and ribociclib (R) 400mg PO QD, D1-D21, Q4wk. Total 13 patients were enrolled in the study. The primary endpoint was treatment-related toxicity and ORR.
Results
There was no dose-limiting toxicity in the 1st (S: 400mg, R: 400mg, n=3) and 2nd (S:400mg, R: 600mg, n=3) dose levels. The dose for expansion cohort (n=7) was S: 400mg Q4wk, R: 600mg D1-D21, Q4wk. From Mar 2020 to Dec 2020, 13 patients were enrolled. The data cut-off was 30 APR 2021. The median follow-up duration was 8.3 months. All patients are male. The cancer types were: oral cavity: 8, oropharynx: 4, hypopharynx: 1. The median age was 53.6 year-old. Eight of 13 patients were ECOG=0. The most common AE were: skin rash (7/13), anemia (5/13), neutropenia (4/13), and creatinine increased (4/13). The most common Gr. 3/4 AE were: neutropenia (3/13), anemia (1/13), thrombocytopenia (1/13), and ALT elevation (1/13). The ORR was 3/13 (23%). The median PFS was 2.1 months (95% CI, 1.0-3.7 months). The median OS is not reached at the time of analysis.
Conclusions
The RP2D is: spartalizumab 400mg iv Q4wk, and ribociclib 600mg PO D1-D21, Q4wk. The toxicity of ribociclib and spartalizumab combination are tolerable. The efficacy of the combination is modest. Further biomarker study is ongoing.
Clinical trial identification
NCT04213404.
Editorial acknowledgement
Legal entity responsible for the study
National Taiwan University Hospital.
Funding
Novartis Taiwan.
Disclosure
H. Kao: Financial Interests, Personal and Institutional, Research Grant: Novartis. All other authors have declared no conflicts of interest.