Pulsed Dose Chemotherapy Plus Pembrolizumab in Recurrent/Metastatic HNSCC

Chemotherapy plus pembrolizumab plays a significant role in standard of care frontline treatment in R/M HNSCC and there is a need for improvement in outcomes with this combination therapy. This trial importantly will test a new dosing and sequence of pembrolizumab and chemotherapy, with the primary goal of improving efficacy but secondarily also has the potential to be better tolerated than standard dosing. Additionally, this trial may have applicability to other solid tumor types where chemotherapy and anti-PD-1 mAb are currently combined. Based on current data showing that current repetitive frequent dosing of chemotherapy may lead to immunosuppression and a detrimental effect on the prolonged duration of response expected from pembrolizumab, and that chemotherapy efficacy may be higher after anti-PD-1 mAb therapy, this trial will test a new sequence starting with pembrolizumab with less frequent dosing of chemotherapy (pulsed dose) to maximize synergy and improve efficacy. Specifically, patients will be treated with pembrolizumab 200 mg IV q3w with carboplatin/paclitaxel given starting with cycle 2 of pembrolizumab and continued thereafter every 3rd cycle of pembrolizumab (q9w) for a total of 4 cycles of carboplatin/paclitaxel. After completion of the 4th cycle of carboplatin/paclitaxel, pembrolizumab maintenance will be continued at 400 mg IV q6w for 12 cycles for a total of 2 years of therapy. Carboplatin/paclitaxel is being used as the chemotherapy doublet in this trial because there is more data for immunogenicity and higher efficacy post anti-PD-1 with taxanes, the potential to be better tolerated than infusional 5-fluorouracil (5FU), and physician preference for this chemotherapy backbone including in our Hillman network. Importantly, prior to the immunotherapy era, a phase III trial compared platinum/taxane to platinum/5FU in R/M HNSCC and found no difference in efficacy between these regimens, and outcomes in combination with pembrolizumab are comparable.