Saulnier-Sholler et al. Page 3950

Previous treatment strategies for medulloblastoma have shown moderate improvement in response. However, the long-term overall survival remains disappointing, and many survivors have profound long-term complications. Therefore, there is a tremendous need to develop novel, improved, and safer therapeutic strategies for medulloblastoma. The critical tumor-stroma interactions mediated by the PlGF/NRP1 pathway make it an attractive target. Sholler and colleagues report a phase I, open-label, multicenter, dose-escalation study of the anti-PlGF antibody, TB-403, in pediatric subjects. TB-403 treatment was well tolerated and induced stable disease in high-risk, heavily pretreated relapsed medulloblastoma allowing for excellent quality of life. These findings indicate that treatment with TB-403 may represent a potentially transformative therapy for children with medulloblastoma and should be tested in larger studies.

Davar et al. Page 3990

Costimulatory molecules expressed on the surface of T cells—such as 4-1BB, OX40, inducible T-cell costimulator (ICOS), and glucocorticoid-induced tumor necrosis factor receptor (GITR)—are potential targets to enhance T-cell antitumor activity. To evaluate the immunomodulatory effects of GITR agonist TRX518, Davar and colleagues designed a phase 1b study evaluating TRX518 alone and in combination with rational partners. While efficacy was modest, the authors consistently observed reductions in Tregs along with CD8+ T cell activation in responders. The pharmacodynamic effects of TRX518 upon Tregs suggests GITR agonism may require additional agents to effect greater Treg modulation and/or simultaneous targeting of alternative T-cell exhaustion pathways for clinical benefit.

Colombo et al. Page 4027

Desmoid fibromatosis (DF) is a rare disease affecting young adults. Spontaneous regression has been described in retrospective series. In this prospective observational study of 108 patients affected by primary sporadic DF primarily managed by active surveillance, Colombo and colleagues report the first prospective confirmation of spontaneous regression followed by regressions even after RECIST progression. They observed spontaneous regression in 56% of the patients (27/108 [25%] as an initial event plus 33/108 [31%] after initial progression). This supports active surveillance as the primary approach to the disease. Patients with larger tumors, extremity location and S45F beta-catenin mutations were at higher risk of receiving an active treatment and may deserve a more intense follow-up.

Johannet et al. Page 4121

Adjuvant immunotherapy produces durable benefit for patients with resected melanoma, but many develop recurrence and/or immune-related adverse events. In this study, Johannet and colleagues analyzed pre-treatment serum from 950 resected melanoma patients from two phase III randomized controlled trials of adjuvant immunotherapy: CheckMate 238 (ipilimumab vs nivolumab) and CheckMate 915 (nivolumab vs ipilimumab plus nivolumab). They identified autoantibody (autoAb) signatures for nivolumab, ipilimumab, and ipilimumab plus nivolumab that could be used to predict disease recurrence and severe immune-related adverse events. The composite panel of autoAb signatures can allow for the simultaneous risk stratification of patients according to their likelihood of recurring and suffering severe toxicity.