In a phase I/II study reported in The Lancet Oncology, Geoerger et al found little activity of atezolizumab alone in pediatric and young adult patients with relapsed or refractory malignancies (including solid tumors, non-Hodgkin lymphoma, and Hodgkin lymphoma) with known or expected programmed cell death ligand 1 expression.

The study included 87 patients (median age = 14 years) from 28 sites in 10 countries who received atezolizumab at 15 mg/kg (younger than 18 years, 80% of population) or at 1,200 mg (18–29 years) every 3 weeks until loss of clinical benefit or disease progression. The most common malignancy types were Ewing sarcoma (11 patients), neuroblastoma (11), osteosarcoma (10), rhabdomyosarcoma (10), Wilms' tumor (10), and Hodgkin lymphoma (9).

Safety Findings

Mean serum concentrations of atezolizumab were comparable between children receiving 15 mg/kg of atezolizumab and young adults receiving 1,200 mg, with concentrations being above target exposure levels in all patients.

The most common adverse events of any grade were pyrexia (41%) and fatigue (36%). The most common grade 3 or 4 adverse event was anemia (22%). Pyrexia was the most common individual serious adverse event (5%); by category, the most commonly reported serious adverse events were infections/infestations. Among immune-mediated adverse events, 12% of patients had events in the infusion-related reaction category, 18% in the hepatitis category, and 5% in the pancreatitis category.

Responses

Objective response was observed in four patients (5%, all partial responses). Ten patients (11%) had stable disease. Responses were observed in two of nine patients with Hodgkin lymphoma, one of three with non-Hodgkin lymphoma, and one of three with malignant rhabdoid tumor.

Data on PD-L1 status and response were available for 63 patients. All 4 responders—and 1 patient with stable disease—were among 11 with high expression (≥ 5% positive tumor cells or ≥ 10% positive immune cell infiltrates). Among the 52 patients with known low or no PD-L1 expression, 7 (13%) had stable disease.

The investigators concluded, “Although response to atezolizumab was restricted, atezolizumab was well tolerated with generally comparable exposure across populations. Our findings might help to define future development strategies for immune checkpoint inhibitors either by focusing research to specific disease subpopulations that exhibit greater benefit from immune checkpoint inhibitors, or by providing the means to identify therapeutic combination partners that augment T-cell infiltration and proliferation in so-called immune cold tumor microenvironments.”

Birgit Geoerger, MD, of Gustave Roussy Cancer Center, Department of Pediatric and Adolescent Oncology, Université Paris-Saclay, Villejuif, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by F. Hoffmann-La Roche. For full disclosures of the study authors, visit thelancet.com.