Sarcoma Awareness Month 2024: Looking Back at a Year of Progress for Cell and Gene Therapy
In observance of Sarcoma Awareness Month, held annually in July, we took a look back at the past year's news in cell/gene therapy for this cancer.
Sarcoma is a type of cancer that affects the body's connective tissue, and as such can appear in any part of the body where this type of tissue is found.1 According to the Sarcoma Foundation of America, sarcoma constitutes 15% to 20% of all cancers in children, but is relatively rare in adults, for whom it constitutes 1% of cancers.
In about half of cases, sarcoma is incurable with currently available treatments, including surgery, chemotherapy, and radiation therapy. As such, great unmet need remains for patients with sarcoma.
An important area of interest for new therapeutic development in sarcoma is cell/gene therapy, which a number of companies and academic institutions are now pursuing. In honor of Sarcoma Awareness Month, observed annually in July by the patient and clinician communities, CGTLive® is taking a look back at the progress that has been made for cell/gene therapy candidates in sarcoma over the past year. Click the "READ MORE" buttons for more details and information about each item.
Lete-cel Study in Synovial Sarcoma, MRCLS Meets Primary Endpoint With 40% ORR
June 5, 2024 — The IGNYTE-ESO (NCT03967223) substudy 2 evaluating letetresgene autoleucel (lete-cel; Adaptimmune) in patients with synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) met its primary endpoint of safety and efficacy at a planned interim analysis, with a 40% overall response rate in evaluable participants.
Data from the substudy were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 - June 4, in Chicago, Illinois, by Sandra P. D’Angelo, MD, sarcoma oncologist, cellular therapist, and associate attending physician, Memorial Sloan Kettering Cancer Center.
“[These data] support the potential of lete-cel as a novel therapy for patients with advanced or metastatic SS and MRCLS. The primary analyses will be presented late 2024 (sic). Further analyses of translational correlates are pending,” D’Angelo said during her presentation.
Tumor Agnostic Deltarex-G+ Gene Therapy Demonstrates Activity in Breast, Pancreatic, Sarcoma Cancers
May 11, 2024 — CCNG1-targeted Deltarex-G gene therapy plus an FDA approved drug (Deltarex-G+) showed some evidence of response in patients’ tumors, including pancreatic cancer, breast cancer, and sarcoma. All tested tumors had enhanced CCNG1 expression.
Data from the BLESSED expanded access study (NCT04091295) were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Erlinda Gordon, MD, founder and president, Aveni Foundation, and director, biological and immunological therapies, and chairman, institutional biosafety committee director, Cancer Center of Southern California/Sarcoma Oncology Center, and founder, chief operating officer, and FDA liaison, Counterpoint Biomedica.
“Deltarex-G is the only tumor targeted gene therapy that can be injected intravenously and it in vivo gets into the tumor microenvironment by binding to abnormal signature proteins in the tumor. So, it's unlike the ex vivo gene therapies for cancer... it's an off the shelf gene therapy product that has a navigation system that goes to the tumor itself,” Gordon told CGTLive during the meeting. “We tested that... CCNG1 is present in all the tumor types that we have tested including sarcoma, pancreatic cancer, breast cancer, testicular cancer, bladder cancer, so that we think it's a tumor agnostic therapy, rather than looking for a very rare oncogene to target."
IL1RAP, CAR, TGFβi, CXCR2 Modified NK Cells Enhances In Vitro Efficacy in Ewing Sarcoma
February 22, 2024 — Modified natural killer (NK) cells (IL1RAP CAR NK, TGFβi-NK, IL1RAP CAR CXCR2 NK) demonstrated enhanced antitumor activity alone and combined with NKTR-255 and dinutuximab against Ewing Sarcoma (ES) tumor cells in vitro, providing rationale for further preclinical study of these cells.
The preclinical data were presented by Wen Luo, PhD, assistant professor, Pediatrics and Pathology, New York Medical College, at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024.
“ES is a malignant pediatric bone associated sarcoma and it is characterized by fusion oncogene in EWS/FLI. Patients with localized ES have around 75% 5-year overall survival (OS) but for patients with metastatic disease, they only have a dismal outcome of around 30% 5-year OS, and patients with relapsed/refractory disease have only 5% 6-month event-free survival. Current treatment including surgery, radiation, and chemotherapy have failed to improve patient outcomes for decades, so novel therapeutics strategies are urgently needed,” Luo said during her presentation.
FDA Accepts Adaptimmune’s BLA for Synovial Sarcoma TCR T-cell Therapy Afami-cel With Priority Review
February 2, 2024 — Adaptimmune Therapeutics’ biologics license application for afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), an investigational T-cell receptor (TCR) T-cell therapy intended to treat SS, has been accepted by the FDA with priority review. The Prescription Drug User Fee Act (PDUFA) target action date has been set for August 4, 2024.
“The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for people with SS,” Adrian Rawcliffe, BSc, the chief executive officer of Adaptimmune, said in a statement. “Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel—the first engineered T-cell therapy on the market for a solid tumor cancer.”
Afami-cel targets MAGE-A4-expressing solid tumors. It is delivered as a single-dose, and intended to treat patients with advanced SS. The majority of patients who are treated with current standard of care therapy for advanced SS experience disease relapse and in many cases they are left with no further FDA-approved treatment options after receiving multiple lines of therapy.
