Feasibility Study Looks at Expanding the Role of NY-ESO-1 Adoptive Cellular Therapy in Advanced Sarcomas and Melanoma

Arun Singh, MD

Arun Singh, MD

Study data involving NY-ESO-1-specific T-cell receptor (TCR) transgenic lymphocytes with an NY-ESO-1 peptide-pulsed DC vaccination in patients with advanced sarcomas and melanoma with (NCTO2070406) or without ipilimumab (NCT01697527) were detailed during a presentation at the 2015 Connective Tissue Oncology Society (CTOS) Annual Meeting.

“This [study] is expanding the role of NY-ESO-1 adoptive cellular therapy. This type of therapy has been used at the National Cancer Institute, and they know it better than everybody else. There have been efforts to do this type of work at other institutions and bring this therapy to other patients,” said presenter Arun Singh, MD, of the Division of Hematology-Oncology at UCLA, in an interview withTargeted Oncology.

Singh presented the interim results of the safety and antitumor efficacy feasibility study, in which study researchers used a previously developed, short (1-week) ex vivo protocol to manufacture NY-ESO-1 antigen-specific T cells.

“The way the people make the immune cells is actually a little cumbersome. It can take weeks to do sometimes, and our project was also trying to see if we could shorten that and make it a much more feasible protocol to do,” said Singh. “Also, we think that combining immunotherapies is better than giving either of them alone.”

In the study, autologous peripheral blood mononuclear cells were transduced with a retroviral vector, encoding an NY-ESO-1—specific TCR and expanded over 2 days in the presence of IL-2. Fresh cells were infused into patients who were HLA-A2.1-positive on day 0 after a regimen of 60 mg/kg cyclophosphamide (day-5, -4) and 25 mg/m²/d (day -4 to -1) fludarabine.

Four patients with synovial sarcoma and one patient each with dedifferentiated liposarcoma, malignant peripheral nerve sheath tumors, and melanoma were enrolled. NY-ESO-1_157-165—peptide-pulsed DC vaccinations were administered on days +1, +14, and +30 and IL-2 was administered at 500,000 IU/m²subcutaneously twice daily for 7 to 14 days. In the NCT02070406 trial, ipilimumab 1 mg/kg was given on day 0 or 1 every 3 weeks for a maximum of 4 doses. Six of the seven enrolled patients received 1 x 10⁹transgenic cells. Mean NY-ESO-1—specific TCR was 55.6% (range, 34.1-71.2). Five of seven patients received 3 DC vaccinations. One of seven patients received 2 vaccinations and one of seven patients received 2 vaccinations. Six patients received 18 to 28 doses of IL-2 (mean 22), and 1 patient received 14/14 doses upon amendment.

Four of six patients showed evidence of a transient response at an early day-30 PET scan. One patient had stable disease (SD) and 1 patient had progressive disease (PD). At day 90, 1 of 6 evaluable patients had partial response (PR), 1 of 6 had SD, and 4 of 6 had PD by RECIST 1.1 criteria. Median follow-up time was 18.7 weeks. At 36 weeks, 1 of 6 patients showed complete response (CR).

Adverse events (AEs) attributed to NY-ESO-1 TCR included anemia (1), rash (1), eosinophilia (1), and one patient experienced a cytokine storm that required hospitalization.

Singh thinks the next steps for this type of study would be to add a PD-1-inhibiting agent (ie, nivolumab [Opdivo]) to NY-ESO-1 adoptive cellular therapy, because of some of the resistance mechanisms that can occur in the tumor microenvironment.

“It’s baby steps; you have to look at all the toxicities and weigh them very carefully to see what makes sense for patients,” he said.

Singh A, Chmielowski B, Berent-Maoz B, et al. Adoptive cellular therapy with autologous lymphocytes genetically modified to express an NY-ESO-1 Specific T-cell receptor and dendritic cell vaccination with or without ipilimumab in patients with advanced sarcomas and melanoma. Presented at: The 2015 Annual Meeting of the Connective Tissue Oncology Society; November 5, 2015; Salt Lake City, UT. Abstract 010.