NCT06052839

Pulsed Dose Chemotherapy Plus Pembrolizumab in Recurrent/Metastatic HNSCC

Phase II Trial of Pulsed Dose Chemotherapy Plus Pembrolizumab in the First Line Treatment of Recurrent/Metastatic HNSCC

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Dan Zandberg · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The rationale for the new sequence of pulsed dose chemotherapy proposed in this trial is based on the hypotheses that current standard dosing of chemotherapy plus pembrolizumab ultimately suppresses the immune system and has a negative effect on the efficacy of the anti-PD-1 monoclonal antibody (mAb) therapy and that chemotherapy given after anti-PD-1 mAb therapy is associated with higher efficacy.

Detailed description

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.

Conditions

• Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Immunotherapy that works by helping the immune system to kill cancer cells by targeting and blocking a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.
DRUG	Carboplatin	A chemotherapy drug that contains the metal platinum. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their DNA.
DRUG	Paclitaxel	A chemotherapeutic agent used as a treatment for various cancers; paclitaxel is a mitotic inhibitor.

Timeline

• Start date: 2023-10-03
• Primary completion: 2026-12-31
• Completion: 2027-12-31
• First posted: 2023-09-25
• Last updated: 2026-02-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study