BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially accessible, treatment-refractory solid tumors.

AdAPT-001 is an investigational therapy consisting of a replicative type 5 adenovirus armed with a TGF-ß receptor-immunoglobulin Fc fusion trap, designed to neutralize isoforms 1 and 3 of the profibrotic and immunosuppressive cytokine, TGF-ß. In preclinical studies with an immunocompetent mouse model, AdAPT-001 eradicated directly treated 'cold' tumors as well as distant untreated tumors, and, from its induction of systemic CD8+ T cell-mediated antitumor immunity, protected the mice from rechallenge with tumor cells. AdAPT-001 also sensitized resistant tumors to checkpoint blockade. This manuscript describes the rationale and design of the first-in-human phase I, dose-escalation and dose-expansion study of AdAPT-001 alone and in combination with a checkpoint inhibitor in adults with treatment-refractory superficially accessible solid tumors.

The purpose of this study is to find out more about the experimental oncolytic virus called AdAPT-001 that has been designed to selectively eliminate cancer cells. The virus is also designed to make a particular protein called a TGF-ß trap, which neutralizes TGF-ß, an overproduced chemical in cancer cells that puts the immune system into a comatose state. This article discusses a clinical trial called BETA PRIME for patients with no other standard treatment options. The trial will explore different doses of AdAPT-001 both alone and in combination with an approved checkpoint inhibitor or another immunotherapy, which blocks the 'off' signal on immune cells, to determine the safest and best dose. Clinical Trial Registration: NCT04673942 (ClinicalTrials.gov).

Evaluation of the optimal sequence of adjuvant chemotherapy and radiation therapy in the treatment of advanced endometrial cancer.

OBJECTIVE: The optimal sequence of adjuvant chemoradiation in the treatment of advanced endometrial carcinoma (EC) remains unclear. We sought to evaluate the outcomes of patients treated with chemoradiation in sandwich fashion (chemotherapy-radiotherapy-chemotherapy; CRC), versus those treated sequentially (chemotherapy-radiotherapy; CR) (radiotherapy-chemotherapy; RC), to determine if there is a survival advantaged associated with a particular treatment sequence. METHODS: A multicenter retrospective analysis of patients with stage III and IV EC from 2000-2018 was conducted. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemoradiation. Differences in the frequencies of adverse events were evaluated using Pearson's χ² test. Progression free survival (PFS) and overall survival (OS) rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 152 patients; 36.8% (n=56) CRC, 28.9% (n=44) CR, and 34.2% (n=52) RC. Histology included 44.0% endometrioid, 47.5% serous and 8.5% clear cell tumors. There was no difference in the frequency of histology (p=0.973), stage (p=0.143), cytoreduction status (p=0.932), or treatment delays (p=0.571) between adjuvant therapy sequences. The most frequent location of disease recurrence was abdomen. The median PFS favored CRC versus CR or RC (36-months vs. 22-months and 24-months, respectively) (p=0.038), as did the median OS (48-months vs. 28-months and 34-months, respectively) (p=0.003). CRC demonstrated superiority over CR and RC sequencing in terms 3-year PFS (55% vs. 34% and 37%, respectively) and 3-year OS (71% vs. 50% and 52%, respectively). CONCLUSIONS: Adjuvant chemoradiation delivered in CRC sequence was associated with improvements in both PFS and OS compared to alternant therapy sequencing.