BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors

Area of Science:

• Oncolytic virotherapy
• Cancer immunotherapy
• Tumor microenvironment modulation

Background:

• Transforming growth factor beta (TGF-β) is an immunosuppressive cytokine.
• Oncolytic adenoviruses (OAVs) are engineered viruses that selectively infect and kill cancer cells.
• AdAPT-001 is an OAV engineered with a TGF-β trap to neutralize its immunosuppressive effects.

Purpose of the Study:

• To assess the safety and tolerability of AdAPT-001 in patients with advanced solid tumors.
• To evaluate the efficacy of AdAPT-001 as a single intratumoral injection (Part 1) and multidose intratumoral injection (Part 2).
• To determine the recommended Phase 2 dose for AdAPT-001.

Main Methods:

• Phase 1, dose-escalation study (Part 1) in 9 patients with varying doses of AdAPT-001.
• Dose-expansion phase (Part 2) in 19 patients receiving AdAPT-001 at 1.0 × 10^12 viral particles (vps).
• Intratumoral injection of AdAPT-001, with efficacy assessed by RECIST 1.1 criteria.

Main Results:

• No dose-limiting toxicities or treatment-related serious adverse events were observed in Part 1.
• Confirmed partial responses in 3 patients and durable stable disease (≥6 months) in 5 patients in Part 2.
• AdAPT-001 demonstrated an anti-tumor effect in both injected and uninjected lesions.
• Recommended Phase 2 dose established as 1.0 × 10^12 vps administered intratumorally every 2 weeks.

Conclusions:

• AdAPT-001 is well-tolerated and shows promising anti-tumor activity in advanced solid tumors.
• The recommended Phase 2 dose of AdAPT-001 is 1.0 × 10^12 vps via intratumoral injection every two weeks.
• Ongoing enrollment for combination therapy with AdAPT-001 and checkpoint inhibitors.