Abstract 4758
Background
HPV induces many alterations in CDK4-Cyclin D-Rb and apoptotic pathways such as up-regulation of p16, loss of Rb and p53 functions in SCCHN carcinogenesis. Loss of p16 expression is known as a poor prognostic marker in SCCHN for survival. Palbociclib is a highly selective inhibitor of CDK4/6 by blocking Rb phosphorylation with radiosensitizing activity in preclinical studies. Addition of palbociclib to cetuximab and IMRT provides a strong rationale to improve efficacy of treatment in locally advanced SCCHN, especially in p16/HPV-negative tumour.
Methods
This is a phase I study designed to determine the maximum tolerated dose (MTD) and toxicity of palbociclib, cetuximab, and IMRT, using a classical 3 + 3 design (NCT03024489). The study included locally advanced SCCHN of oral cavity, oropharynx, larynx, and hypopharynx. Palbociclib dose was escalated with 3 dose levels (DLs), starting from 75 to 125 mg/d orally for 21 day-on and 7 day-off for 2 cycles. For all DLs, cetuximab was administered at 400 mg/m2IV on day -7 and then 250 mg/m2weekly for 7 weeks. IMRT was delivered 5 day-on and 2 day-off with a total dose of 70 Gy for 33 fractions. MRI and PET scans pre- and post-treatment was used to evaluate preliminary efficacy.
Results
A total of 13 eligible patients were enrolled in the dose escalation cohort. No MTD was observed. One DLT, febrile neutropenia (FN) was reported in 1 of 7 patients who received 125 mg of palbociclib (DL3) at the 6thweek of IMRT. The FN recovered without G-CSF support within 7 days after discontinuation of palbociclib. Overall, toxicities were related to cetuximab and IMRT. Complete response was observed in 7 of 10 evaluable patients (70%), while overall objective response was demonstarted in 9 of 10 patients (90%).
Conclusions
The recommended phase 2 dose was palbociclib 125 mg/d for 21 days on and 7 days off with full standard dose of cetuximab and IMRT for locally advanced SCCHN. MTD was not achieved. The combination was well tolerated with promising preliminary efficacy. The expansion cohort of palbociclib 125 mg/d is currently accruing up to 15 locally advanced p16-negative SCCHN patients.
Clinical trial identification
NCT#03024489.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Pfizer.
Disclosure
N. Ngamphaiboon: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Boehringer Ingelheim; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Taiho. T. Siripoon: Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Boehringer Ingelheim. S. Lukerak: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca. N. Sankaseam: Research grant / Funding (institution): Roche; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca. E. Sirachainan: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self): Sanofi/Aventis; Honoraria (self): Merck; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Mundipharma; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): LF Asia; Honoraria (self): Diethelm Keller Logistics; Honoraria (self): BMS; Honoraria (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract
5368 - Durvalumab and Paclitaxel Combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy
Presenter: Hazem Ghebeh
Session: Poster Display session 3
Resources:
Abstract
1520 - A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
Presenter: Daan Hurkmans
Session: Poster Display session 3
Resources:
Abstract
1603 - Safety and clinical activity of subcutaneously (SC) administered anti-PD-1 antibody PF-06801591 in phase I dose-expansion cohorts of locally advanced or metastatic non-small-cell lung cancer (NSCLC) and urothelial carcinoma (UC)
Presenter: Byoung Cho
Session: Poster Display session 3
Resources:
Abstract
3922 - Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A scale to measure quality of life in cancer patients treated with ICMs
Presenter: Aaron Hansen
Session: Poster Display session 3
Resources:
Abstract
2408 - Immune checkpoint inhibitors (ICIs) as “chemotherapy (Ctx) sensitization” strategy in advanced solid tumors
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 3
Resources:
Abstract
3612 - Validation of progression-free survival (PFS) as surrogate endpoint in randomised trials of immune checkpoint inhibitors in advanced solid cancers
Presenter: Peey Sei Kok
Session: Poster Display session 3
Resources:
Abstract
3827 - Pharmacokinetic (PK) analysis of weight-based and fixed dose cemiplimab in patients (pts) with advanced malignancies
Presenter: Michael Migden
Session: Poster Display session 3
Resources:
Abstract
2120 - A burst of highly differentiated CD4 TL identifies a subset of fast progressors, and correlates with hyperprogressive disease in NSCLC patients treated with ICI
Presenter: Hugo Arasanz
Session: Poster Display session 3
Resources:
Abstract
4254 - Nivolumab treatment in advanced non-small cell lung cancer (aNSCLC): a French nationwide retrospective cohort (UNIVOC Study)
Presenter: Christos Chouaid
Session: Poster Display session 3
Resources:
Abstract