Background The prognosis for adult patients with advanced soft tissue sarcomas (STS) is poor and new therapies that improve overall survival are needed. Chemotherapy and targeted therapies offer short-lived disease palliation and control, and the role of checkpoint inhibitors in STS is unclear. We assessed AdAPT-001, an immunotherapy that delivers a TGF-β trap, which binds to and neutralizes the immunosuppressive and profibrotic cytokine, TGF-β, for safety and activity in an ‘all comers, all failed’ population, the majority of which were patients with advanced soft-tissue sarcoma.
Methods In this multicenter, open-label, phase 1 study, we enrolled patients with superficially accessible, relapsed/refractory solid tumors. AdAPT-001 was administered by intratumoral injection at 1x1012viral particles (VPs) once every 2 weeks until progression. Efficacy was evaluated by response (RECIST 1.1). This trial is registered with ClinicalTrials.gov, number NCT04673942.
Results AdAPT-001 was well tolerated with local inflammation, fever, and fatigue as the main side effects. No dose limiting or autoimmune toxicities, grade 4 toxicities, or treatment-related serious adverse events (SAEs) were seen. Out of 25 enrolled patients, 12 had STS. The sarcoma types were leiomyosarcoma (n = 4), chondrosarcoma (n = 1), Mullerian carcinosarcoma (n = 1), chordoma (n = 6). 2 of these STS patients, a chordoma and a leiomyosarcoma, demonstrated durable stable disease (SD) of ≥ 6 months and 1 of the patients with chordoma that was rechallenged with a checkpoint inhibitor after AdAPT-001 objectively responded. Another of the chordoma patients was successfully downstaged and underwent surgical resection. In the leiomyosarcoma patient with durable SD, the injected lesion shrank by 72.2% and evidence of abscopal activity in the non-injected lesions was observed.
Conclusions AdAPT-001 showed encouraging activity in patients with STS. Enrollment to the Phase 2 portion of the study in combination with a checkpoint inhibitor is ongoing.
Trial Registration ClinicalTrials.gov Identifier: NCT04673942
Ethics Approval This study obtained WIRB®ethics approval, under Protocol approval #20203029, and participants gave informed consent before taking part
Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.