Foster et al. Page 3543

Mutations in ALK are common in neuroblastoma, rendering ALK an attractive therapeutic target. Foster and colleagues conducted a phase I/II clinical trial of the ALK inhibitor crizotinib in children with neuroblastoma. Crizotinib was well tolerated in this population. The objective response rate was 15%, with two patients showing a partial response and one patient showing a complete response. Interestingly, all three responders' tumors harbored the same somatic ALK R1275Q mutation. Two additional patients with this mutation had prolonged stable disease, although patients with other hotspot mutations or amplification of ALK did not respond to crizotinib. Further study will elucidate whether third generation ALK inhibitors will prove more effective against a broader spectrum of ALK mutations in neuroblastoma.

Curigliano et al. Page 3620

Although immunotherap. has emerged as an important treatment strategy for many cancers, many patients either do not respond or progress on treatment, indicating that additional strategies for immunotherapy are needed. Curigliano and colleagues performed a phase I clinical trial of sabatolimab, an anti-TIM-3 antibody, with or without spartalizumab, an anti-PD-1 antibody, in patients with solid tumors. A maximum tolerated dose was not reached. Although no responses were observed for sabatolimab alone, combination treatment led to partial responses in 5 patients and prolonged stable responses in 9 patients. Further trials are underway to further determine the therapeutic relevance of TIM-3 in solid and hematologic malignancies.

Shafique et al. Page 3630

Pepinemab is a first-in-class monoclonal antibody that blocks the activity of SEMA4D, a potent regulator of immune cell migration and of the maturation and activity of myeloid suppressor cells. Shafique and colleagues performed a phase Ib/II clinical trial assessing the combination of pepinemab and avelumab, a PD-L1 inhibitor, in patients with lung cancer (the CLASSICAL-Lung trial). This combination was well tolerated and demonstrated antitumor activity in some patients who failed prior therapy with single-agent checkpoint inhibitors as well as in immunotherapy naïve patients with challenging PD-L1 negative or low tumors. These results show promise and warrant additional trials of pepinemab in combination with checkpoint inhibitors in other cancer indications.

Morris et al. Page 3674

PSMA-targeted PET imaging has been considered a promising strategy for detecting prostate cancer that evades standard imaging techniques. Morris and colleagues performed a prospective clinical trial (CONDOR) designed to definitively establish the diagnostic performance of 18F-DCFPyL-PET/CT in patients with biochemical recurrence of prostate cancer and uninformative standard imaging. The trial demonstrated that the radiotracer correctly localized disease in approximately 85% of men, leading to a changed disease management plan in 64% of cases. This study adds greatly to the evidence base in support of the value of PSMA-PET/CT in the management of prostate cancer.