Overview
This is a single arm phase II study that will evaluate the combination of pembrolizumab, docetaxel, and cisplatin or carboplatin (PDC) as single treatment modality in patients with stage II-IVb (T2-4, any N, M0) squamous cell carcinoma of the nasal cavity/paranasal sinuses (PNS SCC).
Description
Primary Objective
-Increase overall response rate (ORR), following pembrolizumab combined with induction chemotherapy prior to radiation, from historical 60% with induction chemotherapy alone to 80%.
Secondary Objective
- Improve the following efficacy endpoints relative to historical results with chemotherapy alone: progression free survival (PFS), overall survival (OS), organ [orbital, maxillary, cranial] preservation rate (OPR), and locoregional failure (LRF).
- To determine safety and tolerability of pembrolizumab combined with induction chemotherapy and chemoradiation in patients with PNS SCC.
- Correlate immune phenotype in tumors and blood, including T cell infiltration and PD-L1 status, with treatment outcomes.
Eligibility
Inclusion Criteria:
- Male/female participants who are at least 18 years of age on the day of signing informed consent with newly diagnosed, previously untreated, histologically and/or cytologically confirmed diagnosis of Stage II-IVb PNS SCC will be enrolled in this study.
- Male participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of this
protocol during the treatment period and for at least 150 days after the last dose of study
treatment and refrain from donating sperm during this period.
-Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix 3),
not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
treatment period and for at least 150 days after the last dose of study treatment.
- The participant (or legally acceptable representative if applicable) provides
written informed consent for the trial.
- Have measurable disease based on RECIST 1.1.
- Have provided archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin
embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies
are preferred to archived tissue.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Have adequate organ function as defined in the following table (Table 1). Blood
must be collected within 14 days prior to the start of study treatment.
Exclusion Criteria:
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment
(see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX 40, CD137).
- Patients must not have received prior systemic anti-cancer therapy including
investigational agents or radiation therapy for PNS SCC but could have received
treatment for prior cancers if greater than 2 years (refer to Item 8 for further
details).