Dr D'Angelo on the Significance of Lete-Cel Treatment Across Sarcoma Subtypes  

“The overall response rate at the primary analysis was 42%...and importantly, the responses do seem to be durable. These results are actually quite compelling when we put them into the context of current standard approved options for patients with synovial sarcoma and myxoid/round cell liposarcoma.”

Sandra P. D’Angelo, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the significance of data from substudy 2 of the phase 2 IGNYTE-ESO trial (NCT03967223) evaluating letetresgene autoleucel (lete-cel) in synovial sarcoma (SyS) and myxoid/round cell liposarcoma (MRCLS).

Substudy 2 of the ongoing, international, open-label IGNYTE-ESO trial is investigating the efficacy and safety of lete-cel in treatment-naive and pretreated patients with NY-ESO-1–expressing advanced or metastatic SyS and MRCLS. A total of 64 patients were treated with lete-cel, 34 of whom had SyS and 30 of whom had MRCLS, D’Angelo details. The median age of the participants was 46 years, which aligns with the typical demographic for these sarcoma subtypes, she says, adding that the majority of enrolled patients (56%) were male.

Findings from the planned interim analysis revealed that among evaluable patients (n = 64), the overall response rate (ORR) was 42%, comprising 6 complete responses and 21 partial responses, D’Angelo reports. The response rates for both sarcoma subtypes were similar, with 41% and 43% of patients with SyS and MRCLS achieving a response, respectively.

Notably, the responses to lete-cel appeared to be durable, D’Angelo continues. The median duration of response (DOR) for the entire cohort was 12.2 months, with patients with SyS experiencing a longer median DOR at 18.3 months. Those with MRCLS had a median DOR of 12.2 months, she states. The median progression-free survival (PFS) was 5.3 months, D'Angelo notes.

Safety data were consistent with previous studies of lete-cel. All patients experienced treatment-emergent adverse effects, the most common of which were cytopenias, cytokine release syndrome, and rash. These toxicities were generally manageable and aligned with the known risk profile of the therapy.

The results of this substudy are compelling, particularly when considered alongside current standard treatment options for SyS and MRCLS, D’Angelo concludes.

Videos

Sandra P. D’Angelo, MD, discusses data from substudy 2 of the phase 2 IGNYTE-ESO trial evaluating lete-cel in SyS and MRCLS.

Sandra P. D’Angelo, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the incidence and prognosis of patients with Merkel cell carcinoma (MCC).

MCC is a rare cancer that affects approximately 1,000 to 2,000 individuals in the United States each year, says D’Angelo. However, like many skin malignancies, the incidence of MCC is rising, D’Angelo explains.

Surgical excision of the tumor remains the standard of care for patients who present with localized MCC, D’Angelo says. Although this is an appropriate course of treatment, a proportion of patients will have disease recurrence and metastasis, D’Angelo explains. Notably, significant research advances have been made in the metastatic setting in recent years for this patient population, concludes D’Angelo.

Sandra P. D’Angelo, MD, discusses the incidence and prognosis of patients with Merkel cell carcinoma. 


Dr. D’Angelo on the Incidence and Prognosis of Merkel Cell Carcinoma 

Sandra P. D’Angelo, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the results of a pilot study investigating the combination of bempegaldesleukin (NKTR-214) plus nivolumab (Opdivo) in patients with sarcomas.

The multicenter study enrolled 50 patients into 9 cohorts: leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), chondrosarcoma (CS) and osteosarcoma (OS), angiosarcoma (AS), alveolar soft part sarcoma (ASPS), synovial sarcoma/small blue round cell, and other. These patients were extensively pre-treated, with 50% of patients having received ≥3 prior therapies, said D’Angelo. The average duration of systemic treatment before enrolling on the trial was about 100 days.

Patients received the combination of bempegaldesleukin (.0006 mg/kg) plus nivolumab (360 mg) every 3 weeks. The combination demonstrated promising activity in various cohorts. Two patients with UPS had a confirmed partial response (PR), along with one patient with CS and one patient with LMS. A decrease in tumor burden was also reported in certain patients.

A good deal of activity with the combination has been observed in those with AS, which is of particular interest because the disease has shown to be responsive to checkpoint inhibitors, says D’Angelo. Of the 5 patients enrolled in this subgroup, there was 1 confirmed PR, 4 patients achieved stable disease, and 2 experienced a decrease in tumor burden.

Several patients with DDLPS were observed to have prolonged disease stability with the combination; this is important as these were patients who had progressive disease prior to trial enrollment, explains D’Angelo.

Based on these results, further exploration of the combination in a treatment-naïve setting is warranted, concludes D’Angelo.

Sandra P. D'Angelo, MD

Articles

Dr D'Angelo on the Significance of Lete-Cel Treatment Across Sarcoma Subtypes

Dr. D’Angelo on the Incidence and Prognosis of Merkel Cell Carcinoma

Dr. D'Angelo on Bempegaldesleukin/Nivolumab Combo in Sarcomas