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Updated: May 27, 2025
Chromogenic In Situ Hybridization as a Tool for HPV-Related Head and Neck Cancer Diagnosis
Published on: June 14, 2019
Novel Combination Immunotherapy and Clinical Activity in Patients With HPV-Associated Cancers: A Nonrandomized
Charalampos S Floudas1, Meghali Goswami1, Renee N Donahue1
1Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Importance:
Patients who experience progression of advanced human papillomavirus (HPV)-associated cancers and who have previously received first-line systemic treatment have a poor prognosis and limited therapeutic options.
Objective:
To assess the clinical activity of the combination of the HPV type 16 therapeutic vaccine PDS0101, the tumor-targeting interleukin 12 antibody-drug conjugate PDS01ADC, and the bifunctional anti-programmed cell death ligand 1 (PD-L1)/transforming growth factor β (TGF-β) bintrafusp alfa in advanced HPV-associated cancers.
Design, Setting, And Participants:
This nonrandomized clinical trial was phase 1/2 and investigator initiated, and was conducted at a single US cancer research center between June 2020 and July 2022. Patients with advanced or metastatic HPV-associated cancers were eligible, including patients who were both immune checkpoint blockade (ICB) naive and ICB resistant. The cutoff date for data analysis was May 13, 2024.
Intervention:
Patients received 1 mL of PDS0101 subcutaneously every 4 weeks for 6 doses then every 12 weeks for 2 additional doses, PDS01ADC, 16.8 µg/kg, subcutaneously every 4 weeks or PDS01ADC, 8 µg/kg, subcutaneously every 2 weeks, and bintrafusp alfa, 1200 mg, intravenously every 2 weeks.
Main Outcomes And Measures:
Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.1 in ICB-naive patients.
Results:
Of the 50 eligible patients, 26 (52%) were men and the median age was 56 years (range, 28-80 years). The median (IQR) follow-up was 37.7 (30.6-42.0) months. Fourteen patients (28%) were ICB naive, with an ORR of 35.7% (95% CI, 12.8%-64.9%), and median overall survival (OS) 42.4 months (95% CI, 8.3 months-not estimable); in ICB-resistant patients, the ORR was 16.7% (6 of 36 patients; 95% CI, 6.4%-32.8%) and median OS was 15.8 months (95% CI, 9.0-21.3 months). Among patients with HPV-16-positive tumors (37 patients [74%]), in the ICB-naive group (8 patients [21.6%]) the ORR was 62.5% (95% CI, 24.5%-91.5%) and a median OS measure was not reached. Grade 3 and 4 treatment-related adverse events occurred in 26 of 50 patients (52%). There were no treatment-related deaths.
Conclusions And Relevance:
In this trial, the combination of PDS0101, PDS01ADC, and bintrafusp alfa showed an acceptable safety profile and promising antitumor activity and improved OS in patients with HPV-16-positive cancers, in both ICB-naive and ICB-resistant patients, warranting further evaluation of the combination of PDS0101 and PDS01ADC with simultaneous PD-L1/TGF-β inhibition in these populations.
Trial Registration:
ClinicalTrials.gov Identifier: NCT04287868.
Insights
This study shows a new combination therapy for advanced HPV-associated cancers is safe and effective, especially for HPV-16-positive tumors. It offers improved outcomes for patients previously treated with immune checkpoint blockade (ICB).
Area of Science:
- Oncology
- Immunotherapy
- Cancer Vaccines
Background:
- Advanced human papillomavirus (HPV)-associated cancers have poor prognoses and limited treatment options after first-line therapy.
- Immune checkpoint blockade (ICB) has shown efficacy, but resistance and progression remain significant challenges.
Purpose of the Study:
- To evaluate the clinical activity and safety of a novel combination therapy for advanced HPV-associated cancers.
- The combination includes the HPV type 16 therapeutic vaccine PDS0101, PDS01ADC (an interleukin 12 antibody-drug conjugate), and bintrafusp alfa (an anti-PD-L1/TGF-β agent).
Main Methods:
- A phase 1/2, investigator-initiated, nonrandomized clinical trial (NCT04287868) was conducted.
- Eligible patients had advanced or metastatic HPV-associated cancers, including those naive or resistant to ICB.
- Treatment involved subcutaneous PDS0101, PDS01ADC (at two dosing schedules), and intravenous bintrafusp alfa.
Main Results:
- The study included 50 patients; 14 were ICB-naive with an objective response rate (ORR) of 35.7% and median overall survival (OS) of 42.4 months.
- In ICB-resistant patients (36), the ORR was 16.7% and median OS was 15.8 months.
- Among HPV-16-positive patients (37), ICB-naive patients (8) had an ORR of 62.5% and did not reach a median OS.
Conclusions:
- The combination of PDS0101, PDS01ADC, and bintrafusp alfa demonstrated acceptable safety and promising antitumor activity.
- The therapy showed improved OS in patients with HPV-16-positive cancers, including both ICB-naive and ICB-resistant populations.
- Further evaluation of this combination, particularly PDS0101 and PDS01ADC with simultaneous PD-L1/TGF-β inhibition, is warranted.
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