PDS0101 Coupled with Pembrolizumab Demonstrated Optimal Efficacy in Recurrent and/or Metastatic HNSCC and High-risk HPV16 Infection

PDS0101 and pembrolizumab Combo

Up to 70% of oropharyngeal cancer in the US are due to be HPV-mediated, with HPV16 infection accounting for the majority of cases. Pembrolizumab, with or without chemotherapy, is the first line of treatment for patients with unresectable, recurrent, or metastatic (R/M) disease, however, the majority of patients eventually experience disease progression. PDS0101 is a vaccine made of liposomal nanoparticles that encapsulate six HPV16 peptides. It is being investigated to stimulate a targeted T-cell response against HPV16-positive tumors.

The combination of PDS0101 and pembrolizumab has received the Fast Track Designation from the US FDA for the treatment of patients with recurrent or metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC).

In a multicenter study initiated by PDS Biotechnology, efficacy, and safety were evaluated. The study enrolled the patients in two cohorts: ICI-naive and ICI-refractory. The primary outcome were the best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) of PDS0101 and pembrolizumab combination, while the secondary outcome were overall survival, progression-free survival (PFS), and incidence of treatment-emergent adverse events using NCI CTCAE in all the patients.

According to the results presented at ASCO 2023, 48 participants who had at least one cycle of combination treatment, had a median age of 62.5 (range, 45-83), were 93.8% male, 93.8% White, and 62.5% ECOG 0. The average treatment duration for this cohort was 3.5 months. 56.3% of patients received 4 doses, whereas 22.9% received 5 doses of PDS0101, the median number of doses (range: 1 to 5). Approximately 27.1% of patients received less than 10 doses of pembrolizumab, with 5 being the median (ranging from 1 to 29). Around 34 individuals (47.1% with combined positive score [CPS] 20) who had assessments of tumor response after therapy had their efficacy assessed. In 23 (67.6%) of the individuals, tumor decrease (highest percent change from baseline) was seen. Fifteen participants had stable disease (44.1%), nine subjects had progressive disease (PD) (26.5%), and nine subjects had confirmed responses (one complete response (CR) and eight partial responses (PR)). One participant (2.9%) could not be evaluated. The PFS was found to be 10.4 months. 

Due to the ongoing survival status of the research participants, the median overall survival among the safety population could not be estimated. The expected 12-month OS rate was 87.1%. The most frequent TEAE (TRAE) associated with PDS0101 were tiredness and injection site reactions (ISRs), affecting 33 (68.5%) participants. Grade III TRAEs were seen in just 3 participants (6.3%) and included tiredness, ISR, elevated blood alkaline phosphatase, and hyperglycemia. No topics have Grade IV or Grade V TRAE. Due to toxicity, no patient was removed from the trial.

KOL insights

“In checkpoint inhibitors (CPI) naive, HPV16-positive, and CPS-positive patients, PDS0101 and pembrolizumab shows early signs of therapeutic benefit in the majority of patients with an acceptable safety profile and permits pembrolizumab dosage to continue” -Expert Opinion.


In this ICI naive R/M HPV-associated HNSCC group, PDS0101 in combination with pembrolizumab was well tolerated. When used as monotherapy in individuals with equivalent PD-L1 levels, the median PFS was 10.4 months, which when compared favorably to published median PFS of 2-3 months for approved ICIs.