ASCO Annual Meeting

ASCO Annual Meeting

Source:

D'Angelo SP, et al. Abstract 11504. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

Disclosures: Adaptimmune supported this study. D’Angelo reports consultant/advisory roles with Adaptimmune, Amgen, EMD Serono, GlaxoSmithKline, Incyte, Immune Design, Immunocore, Merck and Nektar; research funding from Amgen, Bristol Myers Squibb, Deciphera, EMD Serono, Incyte, Merck and Nektar Therapeutics; and travel, accommodations and expenses from Adaptimmune, EMD Serono and Nektar Therapeutics. Please see the abstract for all other researchers’ relevant financial disclosures.
June 04, 2021
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Gene-edited T-cell therapy shows ‘promising efficacy’ for rare sarcomas

Source:

D'Angelo SP, et al. Abstract 11504. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

Disclosures: Adaptimmune supported this study. D’Angelo reports consultant/advisory roles with Adaptimmune, Amgen, EMD Serono, GlaxoSmithKline, Incyte, Immune Design, Immunocore, Merck and Nektar; research funding from Amgen, Bristol Myers Squibb, Deciphera, EMD Serono, Incyte, Merck and Nektar Therapeutics; and travel, accommodations and expenses from Adaptimmune, EMD Serono and Nektar Therapeutics. Please see the abstract for all other researchers’ relevant financial disclosures.
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Nearly 40% of patients with advanced or metastatic synovial sarcoma or myxoid/round cell liposarcoma responded to therapy with afamitresgene autoleucel, according to results of a phase 2 study.

Data from the SPEARHEAD-1 trial, presented during the virtual ASCO Annual Meeting, also showed an 84.8% disease control rate among patients who received the novel gene-edited T-cell therapy.

Nearly 40% of patients with advanced or metastatic synovial sarcoma or myxoid/round cell liposarcoma responded to therapy with afamitresgene autoleucel.
Data were derived from D'Angelo SP, et al. Abstract 11504. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.

Afamitresgene autoleucel (ADP-A2M4; Adaptimmune) — also known as afami-cel — is an autologous, specific peptide-enhanced affinity receptor (SPEAR) T-cell therapy. The agent’s selectively engineered T-cell receptor is designed to target tumors that express the MAGE-A4 protein.

The standard of care for patients with relapsed or refractory sarcoma is cytotoxic chemotherapy, according to Sandra P. DAngelo, MD, a medical oncologist and associate attending at Memorial Sloan Kettering Cancer Center.

Sandra P. D’Angelo, MD
Sandra P. D'Angelo

“These drugs offer some benefit and often stabilize disease for some period of time, but ultimately these patients will pass away from metastatic disease because the responses are often not durable and do not provide an opportunity to go off therapy,” she told Healio.

Afami-cel undoubtedly would be a more durable treatment than the current standard-of-care options and thus far has exhibited “evidence of promising efficacy,” D’Angelo said. The responses seen in the trial are clinically meaningful in the context of standard therapies, she added.

“The data seem promising, and the responses appear to be durable, but there is a need for ongoing follow-up to evaluate these patients further,” D’Angelo said.

D’Angelo and colleagues evaluated the efficacy and safety of afami-cel among patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS).

The SPEARHEAD-1 trial included 37 patients (median age 42 years; range 24-73; 57% men; 87% white) with synovial sarcoma (n = 32) or MRCLS (n = 5) who received an infusion of afami-cel by the data cutoff date of March 29 and were eligible for analysis.

All patients were HLA-A*02-positive, had MAGE-A4 expression on at least 30% of tumor cells, and had previously been treated with either an anthracycline- or ifosfamide-containing regimen. Patients received a median three lines (range, 1-12) of previous systemic therapy.

Patients underwent lymphodepleting chemotherapy followed by an IV infusion of afami-cel at a dose of between 1 × 109 cells and 10 × 109 cells.

Overall response rate as determined by RECIST version 1.1 served as the study’s primary efficacy endpoint. Secondary endpoints included duration of response, PFS and OS. Researchers also evaluated treatment-related adverse events and adverse events of special interest.

Ninety-five percent of patients had at least one treatment-related adverse event, the most common of which included cytopenias.

“Adverse events do occur and almost all were tolerable and addressable,” D’Angelo said, adding that nearly all patients had complete resolution of adverse event-related symptoms.

This included patients who experienced cytokine release syndrome, which she said resolved and improved over time with the use of tocilizumab (Actemra, Genentech).

Twenty-two patients (59%) experienced CRS, but only one patient had grade 3 or greater CRS. Median time to onset of CRS was 3 days (range, 1-9), with a median time to CRS resolution of 3 days (range, 1-34).

Efficacy results showed an ORR of 41.4% for patients with synovial sarcoma and 25% for those with MRCLS, for a 39.4% ORR for the entire study population. Two patients with synovial sarcoma had a complete response to therapy as of the data cutoff date.

The disease control rate was 84.8% across the study.

Median OS, duration of response and PFS had yet to be reached.

“We hope the durability remains in further study of afami-cel to achieve that goal of FDA approval,” she told Healio. “Having an FDA-approved agent would add to our treatment options.”

FDA approval of afami-cel would allow patients to be treated with a cell infusion that could help them remain off therapy and would have a remarkable impact on quality of life, D’Angelo said.

“These are important data that will hopefully continue to evolve and offer a new standard of care for our patients in the near future,” she said.