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Background AdAPT-001 is an oncolytic adenovirus armed with a transforming growth factor beta (TGFβ) trap that induces inflammation while blocking TGFβ locally within cancers. The Beta Prime clinical trial evaluates the activity of AdAPT-001 used alone or in combination with CI in refractory solid tumors, including tumors that have failed to respond or progress on CI treatment. Clinical data demonstrate that AdAPT-001 induces a tumor-specific inflammatory response, reverses the tumor immune evasion phenotype and improves the efficacy of immune checkpoint therapy, increasing response rate and progression-free survival (PFS) and overall survival (OS) in CI refractory tumors including angiosarcoma.Methods Patients with CI-refractory solid cancers received AdAPT-001 with a concurrent checkpoint inhibitor. Response was assessed every 8 weeks using RECIST 1.1. Treatment beyond progression was allowed for patients clinically benefiting, and if progression was confirmed on the next assessment then the first assessment meeting PD criteria was considered the date of progression. PFS on AdAPT-001 + CI was compared to duration of treatment on the most recent previous regimen including a CI before study enrollment.Results Among all patients who were treated with a CI in a previous line of therapy (Prior CI) before being treated with AdAPT-001 + CI, the 6-month PFS rate was 17% (3/18) with Prior CI and 33% (6/18) with AdAPT-001 + CI, and the 12-month PFS rate was 0% (0/18) with Prior CI and 17% (3/18) with AdAPT-001 + CI. Particular activity was seen in angiosarcoma, where all patients progressed within 3 months on Prior CI and 75% (3/4) had PFS >11 months with AdAPT-001 + CI. Treatment with AdAPT-001 was well tolerated and no new safety signals emerged.Conclusions The data from this P2 clinical trial strongly suggests that AdAPT-001 circumvents resistance to CIs in multiple tumor types, improving PFS when compared to the patient’s prior CI regimen. Extensive immune-mediated destruction, including pathological complete response of the primary tumor and metastatic lesions ( figure 1), were observed without significant regional or systemic toxicity. In addition, AdAPT-001 may prevent the development of CI-induced autoimmune toxicities. PBMC treatment with AdAPT-001 induces PD-L1 expression on macrophages. This supports a proposed mechanism of action where infection with AdAPT-001 induces both immunogenic and regulatory responses including PD-L1 and blocking the PD-L1 that is induced during treatment will shift the pro- and anti-inflammatory balance toward a productive immune response, even in cancers that are not inherently sensitive to anti-PD(L)1 at baseline.Abstract 607 Figure 1Pathologic complete response