• Study indicates clear route to market despite not meeting the primary endpoint of 6 months’ overall response rate (ORR) in the entire population
  • In a predefined subgroup of patients there was a doubling of ORR (51.9% vs 26.7% for placebo) and improved overall survival which sets the stage for a confirmatory Phase 3 trial

OEGSTGEEST, The Netherlands I December 12, 2023 I ISA Pharmaceuticals B.V. (ISA), a clinical-stage immunotherapy company, today announced positive anti-tumor response data with ISA101b, an HPV16 directed therapeutic cancer vaccine given in combination with Libtayo®, an anti-PD1 checkpoint inhibitor (CPI).  The data were generated in the OpcemISA trial, a large scale randomized double blind study that is ongoing in patients with advanced oropharyngeal cancer (OPC), a type of head and neck cancer. It is the first time that the combination of a tumor-specific therapeutic vaccine and a CPI has generated such high response rates, albeit in a predefined subpopulation of metastatic cancer patients.

ISA101b is a therapeutic cancer vaccine targeting cancers caused by the human papillomavirus type 16 (HPV16). More than 60 percent of head-and-neck cancers are HPV16-related, and incidence rates are going up. ISA101b elicits a powerful and targeted T-cell immune response to the HPV16 virus.

OPC is a solid cancer with a high unmet medical need that does not always respond to immunotherapy. Best responses in the OpcemISA trial are found in a subcategory of patients with characteristics suitable for immunostimulatory treatments.

Study design & results
A total of 199 first- and second-line patients with recurrent/metastatic HPV16+ OPC were enrolled in the OpcemISA trial. Patients were randomized to receive either ISA101b plus CPI, or placebo plus CPI. The primary endpoint was the objective response rate (ORR) at 6 months, confirmed by independent central review. The secondary endpoints included drug safety, progression free survival (PFS) and overall survival (OS). Further details can be found at clinicaltrials.gov (NCT03669718).

Whereas the addition of ISA101b to the CPI led to a doubling of the ORR (from 26.7% to 51.9%) in a large subgroup of patients, the study as a whole did not meet this primary endpoint. Patients in the aforementioned subgroup, predefined based on a validated biomarker, also showed a clear overall survival benefit compared to the placebo arm. ISA101b was well tolerated.

Gerben Moolhuizen, Chief Executive Officer of ISA, said, “Recurrent and/or metastatic head and neck cancer is notoriously difficult to treat. Patients suffering from this terrible disease need new treatment options. In our OpcemISA study, ISA101b shows compelling results in a large, predefined subset of patients. This provides us with a clear development path to make ISA101b a treatment option for these patients.”

Phase 3 and beyond
ISA is preparing for a confirmatory Phase 3 trial in this subpopulation of patients. This subgroup represents an important proportion of head and neck cancer patients, and an attractive commercial opportunity. The OpcemISA trial was part of a clinical collaboration between ISA and Regeneron. Regeneron has elected not to exercise its option on the ISA101b asset. ISA is currently in discussions with potential partners with interest in ISA101b and ISA’s technology platform in general.

About ISA Pharmaceuticals
ISA Pharmaceuticals is an immunotherapy company developing treatments for various cancers and infectious diseases. ISA has best-in-class technology to stimulate and activate the human immune system, specifically T cells, to fight diseased or infected cells. Its lead asset ISA101b is in late-stage clinical trials for human papillomavirus type 16 (HPV16)-induced cancers in a collaboration with biotechnology company Regeneron. Other assets are in preclinical stage development and include immunotherapies to treat patients that suffer from cancers that over-express PRAME or chronic hepatitis B. For more information, please visit www.isa-pharma.com.

About ISA101b
ISA101b immunotherapy targets human papillomavirus type 16 (HPV16) positive cancers. It induces strong and specific T-cell immune responses to the HPV16 virus, and (re-)establishes a powerful and targeted T-cell immune response against infected and/or cancerous cells and tissues. ISA101b is using ISA’s proprietary Synthetic Long Peptide (SLP®) technology.. In September 2021 ISA101b was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of recurrent and metastatic HPV16 positive oropharyngeal cancer (OPC).

SOURCE: ISA Pharmaceuticals