Cell Therapy Combination Shows Antitumor Response in Ewing Sarcoma

Data from a phase 2 study (NCT02511132) have demonstrated safety of Vigil cell therapy (Gradalis) in combination with temozolomide (TEM) and irinotecan (IRI) in participants with recurrent/refractory Ewing sarcoma (ES) after standard of care treatment.¹

“While treatment options for recurrent or refractory ES are limited, we are encouraged by the potential of Vigil in combination with TEM/IRI to contribute to antitumor activity and address the unmet need for these patients,” John Nemunaitis, MD, Chief Scientific Officer, Gradalis, said in a statement.² “Results in this publication demonstrated the efficacy of Vigil in combination with TEM/IRI, which was highlighted by corresponding changes in ctDNA levels. This builds on our previous research involving multiple recurrent disease patients who achieved 75% one-year survival compared to historical expected survival of only 23%. Together with the growing safety data, results support future evaluation of Vigil-based combinations in multiple solid tumor types and use of sensitivity biomarkers to track disease response. We look forward to further utilizing ctDNA assessment tools in our ES investigation and beyond.”

First author Peter Anderson, MD, Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic, and colleagues enrolled 10 participants in the trial, 8 of which were evaluable for safety and efficacy. These 8 participants had a mean age of 24.6 years (range, 12.6 - 46.1) and 6 received the Vigil/TEM/IRI combination, which consisted of 100 mg/m² per day of oral TEM and 50 mg/m² per day of oral IRI during days 1 through 5 and 1x10⁶ to 1x10⁷ cells/mL per day of intradermal Vigil on day 15, every 21 days.¹ Treatment was discontinued when patients progressed, experienced unacceptable toxicities, or exhausted all constructed Vigil doses (4-12 constructed per patient). Seven participants had previously received TEM/IRI treatment.

READ MORE: Bringing Solid Tumors into the Cell Therapy Space

Investigators observed no adverse events (AEs) related to Vigil. Common chemotherapy-related AEs of at least grade 3 included neutropenia (50%) and thrombocytopenia (38%). Two participants had partial responses by RECIST and histologic complete responses without additional therapy at long-term follow-up. The mean progression free survival was 8.2 months (95% CI, 4.3-NA), 1-year overall survival (OS) rate was 62.5% (95% CI, 36.5–100), and median OS was 18.5 months (95% CI, 8.2–NA). In total, 5 participants experienced at least stable disease for at least 6 months. Investigators were also able to detect circulating tumor DNA in all evaluable patients at baseline and level changes corresponded to changes in disease burden. Median follow-up time was 18.5 months (range, 5.7–29.5).

Vigil is an autologous tumor cell therapy that expresses bi-shRNA furin/GMCSF plasmid. It has also been evaluated as a monotherapy in patients with ovarian cancer in the phase 2 VITAL trial (NCT02346747), in which promising antitumor activity was observed.

“Management of recurrent or refractory ES is limited particularly in patients who have already failed treatment with TEM/IRI. Observation of 2 PRs and 3 prolonged SD in patients who have previously failed prior TEM/IRI to the Vigil/TEM/IRI regimen support proof of principle that Vigil may contribute to antitumor activity with TEM/IRI in ES,” Anderson and colleagues concluded.¹

REFERENCES

1. Anderson P, Ghisoli M, Crompton DB, et al. Pilot study of recurrent Ewing's sarcoma management with vigil/temozolomide/irinotecan and assessment of circulating tumor (ct) DNA. Clin. Cancer Res. Published online March 16, 2023. doi: 10.1158/1078-0432.CCR-22-2292
2. Gradalis announces publication in clinical cancer research featuring positive results from a study evaluating vigil® in combination therapy for patients with recurrent Ewing's sarcoma. News release. March 14, 2023. https://www.globenewswire.com/news-release/2023/03/14/2626549/0/en/Gradalis-Announces-Publication-in-Clinical-Cancer-Research-Featuring-Positive-Results-from-a-Study-Evaluating-Vigil-in-Combination-Therapy-for-Patients-with-Recurrent-Ewing-s-Sarco.html