Selected Articles from This Issue

The prognosis for patients diagnosed with epithelial ovarian cancer remains poor, especially in those patients resistant to platinum therapy. Evidence has suggested that the Wee1 inhibitor adavosertib may be efficacious in combination with chemotherapy. Moore and colleagues conducted a clinical trial of adavosertib combined with four commonly used chemotherapeutics in patients with primary platinum-resistant ovarian cancer. Combinations were effective, with 3% of patients achieving a complete response and 29% of patients with partial response. The response rate was highest with adavosertib plus carboplatin, while the longest duration of response was observed in patients treated with adavosertib plus paclitaxel. However, many patients experienced toxicity. These results indicate that although adavosertib may have promise for the treatment of ovarian cancer, further clinical study is necessary to minimize toxicity.

Checkpoint inhibitors have improved outcomes in patients with many cancer subtypes, but resistance to treatment remains a challenge. In this clinical trial, Siu and colleagues assessed MK-4830, a first-in-class monoclonal antibody targeting the immunoglobulin-like transcrip. R (ILT4) receptor, either as monotherapy or in combination with the PD-1 inhibitor pembrolizumab. No dose-limiting toxicities were observed, and maximum-tolerated dose was not reached. Furthermore, promising clinical activity was observed with 11/34 patients receiving combination therapy achieving objective responses. Patients with evidence of T-cell inflammation were more likely to respond. Further study of this novel agent is warranted in additional clinical trials.

Preclinical work has suggested that OX40 agonism may promote anti-tumor immunity, leading to effective antitumor responses. In this study, Diab and colleagues conducted a clinical trial assessing ivuxolimab, a monoclonal antibody against OX40, in patients with advanced solid tumors. Ivuxolimab was well tolerated, with no dose-limiting toxicities. Preliminary antitumor activity was observed, with disease control occuring in 56% of patients. Evidence of immune activation was observed in peripheral blood, as well as in on-treatment biopsies. Further clinical trials of ivuxolimab are warranted, especially in the combination setting.

Stereotactic body radiotherapy (SBRT) is an emerging local treatment strategy for pancreatic ductal adenocarcinoma (PDAC). To characterize SBRT effects on the human tumor immune microenvironment, Mills and colleagues analyzed resected PDAC tissue a median seven days post-treatment. SBRT induced immunogenic cell death and initiated antitumor immune responses; however, treatment failed to lessen or reprogram abundant immune suppressor populations. SBRT did not improve clinical survival outcomes, but the augmentation of antitumor immunity supports and informs the continued development of SBRT/immunotherapy combinations for PDAC.