Combining the experimental vaccine galinpepimut-S (GPS) with the immune checkpoint inhibitor Keytruda (pembrolizumab) induces promising responses in people with metastatic ovarian cancer who failed one or two prior lines of treatment, early data from a Phase 1/2 trial show.
The combination kept all eight patients in a first evaluated group in the trial (NCT03761914) without signs of disease progression for at least six weeks, and had a similar safety profile to that of Keytruda alone.
The trial is recruiting ovarian cancer patients at multiple sites across the U.S. Eligible participants are those with ovarian, fallopian tube or primary peritoneal cancer who failed prior platinum-based chemotherapy, and were offered bevacizumab treatment. If a patient carries BRCA mutations, treatment with a PARP inhibitor must also have been offered.
“These safety findings are accompanied by promising early indications of an efficacy signal for patients with advanced metastatic disease, whose management is extremely challenging even with checkpoint inhibitor monotherapy,” Jeffrey S. Weber, MD, PhD, chair of the scientific advisory board for Sellas Life Science, the vaccine’s developer, said in a press release.
GPS is an investigational vaccine that targets the WT-1 protein, one of the most common cancer-associated proteins. It contains four small proteins aiming to elicit a strong innate immune response against WT-1, increasing the immune system’s ability to destroy cancer cells.
Like a conventional vaccine, GPS is also meant to trigger an “immunological memory,” empowering the immune system with the ability to stop tumors from coming back.
“GPS has previously been shown to invoke multi-epitope, broad cross-reactivity along the full-length of the WT1 protein, suggestive of epitope spreading, and immunologically mediated cancer cell destruction, which are hallmarks of an effective cancer vaccine,” said Dragan Cicic, MD, senior vice president, clinical development of SELLAS.
Keytruda, by Merck (known as MSD outside North America), belongs to the class of immune checkpoint inhibitors, and works to block mechanisms used by cancer cells to avoid immune attacks.
Combining these two therapies is expected to unleash a full-blown immune response, overcoming the immunosuppressive influence of the environment around a tumor (microenvironment).
“The scientific rationale in combining GPS with checkpoint inhibitors is the … synergy between the two agents, whereby the negative influence of the tumor microenvironment is mitigated by checkpoint inhibitors and thus allowing the patients’ own immune cells specifically sensitized against WT1, by GPS, to invade and destroy cancerous cells,” Cicic added.
The Phase 1/2 trial is exploring this combination in multiple solid tumors and in leukemia, a blood cancer. The ovarian cancer group is expected to enroll 20 women whose metastatic disease has relapsed or is refractory to one or two prior lines of therapy.
Its main goals are to determine the safety of the combination, and the proportion of patients attaining partial or complete responses to treatment. Secondary measures include the time to disease progression or death, overall survival, and immune responses.
Results from the first eight ovarian cancer patients eligible for evaluation showed that seven (87.5%) had at least disease stabilization after a median follow-up of 9.4 weeks. At the first assessment, at six weeks, all patients were free of disease progression.
About 70% of these patients were positive for WT-1 in their tumor samples. Six of the eight evaluable patients are continuing to receive the combo therapy.
The combination’s safety profile was similar to that seen with immune checkpoint inhibitors alone, with the exception of mild, reversible local reactions at the injection site of GPS.
Additional trial data are expected by June, the company noted.
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