AdAPT-001 Gets FDA Fast Track Designation in Recurrent/Refractory Soft Tissue Sarcoma

The FDA has granted fast track designation to AdAPT-001 in combination with nivolumab (Opdivo) or atezolizumab (Tecentriq) for the treatment of patients with recurrent or refractory advanced or metastatic soft tissue sarcoma who experience disease progression following 1 or more prior lines of therapy.1

The designation was supported by data from the phase 1/2 BETA-PRIME study (NCT04673942).2 Findings from the trial presented during the 2024 ASCO Annual Meeting showed that response-evaluable patients with soft tissue sarcoma who received AdAPT-001 in combination with an immune checkpoint inhibitor (n = 14) achieved an overall response rate (ORR) of 21% per RECIST 1.1 criteria and 36% per clinical assessment. The 6-month progression-free survival (PFS) rates among evaluable patients (n = 13) were 38% per RECIST 1.1 criteria and 54% per clinical assessment. The median PFS was not yet reached among patients with sarcoma.

“Checkpoint blockade immunotherapies have revolutionized cancer therapy for many patients and prolonged the lives of millions. [However], efficacy depends on the presence of an immune infiltrate, which is often absent or immunosuppressive, and low levels of immunosuppressive factors like TGFβ, which are frequently overexpressed,” Tony Reid, MD, PhD, chief executive officer, chief scientific officer, and cofounder of EpicentRx, said in a news release.1 “AdAPT-001 is designed both to inflame the tumor microenvironment and to combat immunosuppression by neutralization of TGFβ through the expression of a TGFβ trap. Fast track designation is a terrific acknowledgement of the potential of AdAPT-001 to make a meaningful difference for [patients with] soft tissue sarcoma who desperately require new treatment options."

AdAPT-001 is TGFβ inhibitor that is delivered via an oncolytic adenovirus, and it is designed to express a potent TGFβR inhibitor for local TGFβ neutralization, decreased regulatory T-cell function, and an enhanced therapeutic response when administered with checkpoint inhibitors. The agent is intended for use in several tumor types, including soft tissue sarcoma, colorectal cancer, breast cancer, and hepatocellular carcinoma.

BETA-PRIME enrolled adult patients with injectable solid tumors who had received all appropriate conventional therapies.2 Eligible patients needed to have an ECOG performance status of 2 or less and acceptable lab values. Those who had uncontrolled active infections, underwent prior adenovirus therapy, and had autoimmune disease requiring over 10 mg per day of prednisone equivalent within 14 days of enrollment were excluded.

Part 1 of the study followed a 3+3 dose escalation to 1 x 1012 vp where AdAPT-001 was administered via a single dose. In part 2, AdAPT-001 monotherapy was given at a dose of 1 x 1012 vp every 2 weeks; in part 3 patients received AdAPT-001 at the same dosing schedule in combination with an optional immune checkpoint inhibitor given via standard-of-care dosing starting at week 5. In all parts, AdAPT-001 was injected intratumorally, and treatment beyond disease progression was permitted.

The overall treatment population (n = 25) was mostly comprised of patients who were less than 65 years old (56%), male (64%), and White (80%). Tumor types included sarcoma (56%), head and neck cancer (24%), melanoma (12%), and breast cancer (8%). Most patients received a prior checkpoint inhibitor (72%); patients underwent 1 (16%), 2 (12%), 3 (24%), 4 (20%), 5 (20%), or 6 or more (8%) prior regimens. Patients received checkpoint inhibitor therapy with pembrolizumab (Keytruda; n = 8), nivolumab (n = 9), atezolizumab (n = 7), or cemiplimab-rwlc (Libtayo; n = 1).

Additional findings from BETA-PRIME demonstrated that 1 patient with chordoma and another with angiosarcoma continued with treatment beyond disease progression. Overall, 7 patients were in ongoing treatment at the data cutoff. Five patients with sarcoma who received AdAPT-001 with a checkpoint inhibitor were in ongoing treatment, including 1 who received treatment beyond disease progression.

In terms of safety, no dose-limiting toxicities or serious adverse effects (AEs) related to AdAPT-001 were reported. One immune-related AE occurred among patients who received a checkpoint inhibitor, and there was no toxicity in normal tissue adjacent to injected tumors. Grade 1 or 2 AEs deemed related to AdAPT-001 included flu-like symptoms (84%), which resolved with 1 to 2 days of dosing, and injection site reactions (24%), all of which were grade 1 in severity. There was no significant nasopharyngeal viral shedding, and all injection site shedding cleared within 4 weeks of administration of AdAPT-001.

References

1. EpicentRx’s oncolytic virus-delivered TGFβ inhibitor, AdAPT-001, receives FDA fast track designation for recurrent or refractory soft tissue sarcoma treatment. News release. EpicentRx. December 5, 2024. Accessed December 6, 2024. https://www.epicentrx.com/2024/epicentrxs-oncolytic-virus-delivered-tgf%ce%b2-inhibitor-adapt-001-receives-fda-fast-track-designation-for-recurrent-or-refractory-soft-tissue-sarcoma-treatment-3/
2. Conley AP, Ravi V, Rolan CL, et al. Phase 1/2 study of the TGF-β-trap-enhanced oncolytic adenovirus, AdAPT-001, plus an immune checkpoint inhibitor for patients with immune refractory cancers. J Clin Oncol. 2024;42(suppl 16):2506. doi:10.1200/JCO.2024.42.16_suppl.2506