TY - JOUR
T1 - BETA prime
T2 - a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors
AU - Conley, Anthony P.
AU - Roland, Christina L.
AU - Bessudo, Alberto
AU - Gastman, Brian R.
AU - Villaflor, Victoria M.
AU - Larson, Christopher
AU - Reid, Tony R.
AU - Caroen, Scott
AU - Oronsky, Bryan
AU - Stirn, Meaghan
AU - Williams, Jeannie
AU - Burbano, Erica
AU - Coyle, Angelique
AU - Barve, Minal A.
AU - Wagle, Naveed
AU - Abrouk, Nacer
AU - Kesari, Santosh
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2024/4
Y1 - 2024/4
N2 - AdAPT-001 is an oncolytic adenovirus (OAV) with a transforming growth factor beta (TGF-ß) trap, which neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single intratumoral injection (IT) (Part 1) and multidose IT injection (Part 2) in patients with superficially accessible, advanced refractory solid tumors. Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.5 × 1011, 5.0 × 1011, 1.0 × 1012 viral particles (vps). No dose-limiting toxicities or treatment-related serious adverse events (SAEs) were seen. In Part 2, a dose-expansion phase, 19 patients received AdAPT-001 at 1.0 × 1012 vps until disease progression according to Response Evaluation Criteria in Solid Tumors or RECIST 1.1. The overall responses to treatment included confirmed partial responses (3), durable stable disease ≥ 6 months (5), and progressive disease (13). AdAPT-001 is well tolerated. Evidence of an anti-tumor effect was seen in both injected and uninjected lesions. The recommended Phase 2 dose was 1.0 × 1012 vp administered by intratumoral injection once every 2 weeks. Combination of AdAPT-001 with a checkpoint inhibition is enrolling.
AB - AdAPT-001 is an oncolytic adenovirus (OAV) with a transforming growth factor beta (TGF-ß) trap, which neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single intratumoral injection (IT) (Part 1) and multidose IT injection (Part 2) in patients with superficially accessible, advanced refractory solid tumors. Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.5 × 1011, 5.0 × 1011, 1.0 × 1012 viral particles (vps). No dose-limiting toxicities or treatment-related serious adverse events (SAEs) were seen. In Part 2, a dose-expansion phase, 19 patients received AdAPT-001 at 1.0 × 1012 vps until disease progression according to Response Evaluation Criteria in Solid Tumors or RECIST 1.1. The overall responses to treatment included confirmed partial responses (3), durable stable disease ≥ 6 months (5), and progressive disease (13). AdAPT-001 is well tolerated. Evidence of an anti-tumor effect was seen in both injected and uninjected lesions. The recommended Phase 2 dose was 1.0 × 1012 vp administered by intratumoral injection once every 2 weeks. Combination of AdAPT-001 with a checkpoint inhibition is enrolling.
UR - http://www.scopus.com/inward/record.url?scp=85180495739&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85180495739&partnerID=8YFLogxK
U2 - 10.1038/s41417-023-00720-0
DO - 10.1038/s41417-023-00720-0
M3 - Article
C2 - 38146006
AN - SCOPUS:85180495739
SN - 0929-1903
VL - 31
SP - 517
EP - 526
JO - Cancer gene therapy
JF - Cancer gene therapy
IS - 4
ER -