The following summary is “A Phase I/II Trial of Nivolumab plus Ipilimumab in Children and Young Adults with Relapsed/Refractory Solid Tumors: A Children’s Oncology Group Study ADVL1412” published in the December 2022 issue of Oncology by Davis et al.
Although the combination of nivolumab and ipilimumab has been shown to boost response rates in various malignancies, its efficacy in children’s cancer has not yet been determined. Researchers evaluated the combination of nivolumab and ipilimumab in phase I/II trial in children and young adults with recurrent/refractory solid malignancies. 2 dose levels (DL) of nivolumab and ipilimumab were tested for safety in ADVL1412, Part C: DL1 consisted of 1 mg/kg of each drug, and DL2 consisted of 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab.
Part D looked at how well Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma responded to the RP2D. Ewing sarcoma and rhabdomyosarcoma were the targets of the DL3 study (1 mg/kg nivolumab plus 3 mg/kg ipilimumab). The RECIST v1.1 was used to evaluate tumor response. In addition, archival tissues were examined for PD-L1 expression and pharmacokinetics. About 55 patients who qualified for the study did so. For children, DL2 is the RP2D because it has been shown to be safe and well tolerated at levels that would produce equivalent exposure in adults. There were 2 patients who encountered dose-limiting toxicities (DLT) during cycle 1 of treatment at the RP2D, and 4 patients who experienced toxicities beyond cycle 1.
Only 1 patient with rhabdomyosarcoma and another with Ewing sarcoma experienced a clinically meaningful persistent partial response, and 4 others had a stable illness. Of the 8 patients who received treatment at DL3, 3 experienced DLT, all of which were immune-related side effects; no objective responses were noted. It has been found that the RP2D of nivolumab (3 mg/kg) with ipilimumab (1 mg/kg) is well tolerated and has some therapeutic activity in adolescents and young adults with solid malignancies. Toxicities increased with higher ipilimumab and nivolumab doses, but no further therapeutic benefit was seen.