The invited discussant of the VERSATILE-002 and CUE-101-01 trials, Erminia Massarelli, MD, PhD, MS, said both are examples of a growing interest in evaluating immunotherapeutic strategies and treatment sequences in early-stage head and neck squamous cell cancer as well as in metastatic disease. Dr. Massarelli is Associate Professor, Department of Medical Oncology & Therapeutics Research and Section Chief of Thoracic Oncology at City of Hope, Duarte, California.
PDS0101, which was evaluated in VERSATILE-002, has an “interesting mechanism of action for increasing immunogenicity,” she noted, and the outcomes “were encouraging in human papillomavirus [HPV]-positive head and neck cancers,” although the study was small and the data still immature. For most responders, the responses occurred within 60 to 90 days and were maintained, except for one patient who experienced disease progression within the year. At 12 months, 87% of patients were alive: “When paired with the KEYNOTE-048 historical data, this is an impressive overall survival rate…. The toxicity for the treatment duration was also comforting…, and these injections are subcutaneous,” she observed.
Commenting on CUE-101-01, Dr. Massarelli said she “gives kudos” to the investigators for obtaining HPV cell-free DNA data on 11 patients. They were collected at baseline and prior to each treatment cycle. “What was interesting is that in four of the five patients with HPV cell-free DNA and confirmed partial responses, HPV cell-free DNA was not detectable within 6 weeks of treatment initiation,” she noted.
“We did see longer median overall survival (22.4 months) as compared with historical data. However, the small sample size can lend bias…. The toxicity was a bit higher than I expected, with ≥ grade 3 toxicities seen in 48% receiving the combination. This consisted mainly of fatigue, anemia, chills, and nausea, which are probably related to infusion reactions,” Dr. Massarelli commented. “Also, in the real world, restricting treatment by HLA genotype can be a real problem, as it can be costly and associated with a high rate of screen failure.”
To move PDS0101, CUE-101, and other novel compounds forward in squamous cell carcinoma of the head and neck, Dr. Massarelli added, “our challenge is to identify predictors of response, especially in the curative-intent setting.”
DISCLOSURE: Dr. Massarelli reported financial relationships with AbbVie, Bristol Myers Squibb, Daiichi Sankyo, Genentech/Roche, Janssen, Eli Lilly, Merck, Sanofi, AstraZeneca, Mirati Therapeutics, and Takeda.
