Children, adolescents, and young adults with relapsed or refractory cancers — particularly those with lymphoma — have better responses to Genentech‘s immune checkpoint inhibitor Tecentriq (atezolizumab) if they have high levels of the PD-L1 factor in their tumors, a study found.
The findings will be presented during the upcoming American Association for Cancer Research (AACR) Annual Meeting, in Atlanta, Georgia. The study is titled “Correlation between response to atezolizumab and PD-L1 tumor expression in pediatric and young adult patients enrolled in the phase I/II iMATRIX-atezo study.”
Tecentriq is an immune checkpoint inhibitor that targets the PD-L1 protein and prevents it from binding to the PD-1 receptor on immune cells. Cancer cells use this binding to prevent the immune system from recognizing them as foreign. As such, Tecentriq is capable of restoring immune surveillance.
Tecentriq is already approved in the U.S. for adults with non-small cell lung cancer, triple-negative breast cancer, and bladder cancer, either alone or in combination with other treatments. However, whether this treatment is also effective in pediatric and young adult patients remains unknown.
The iMATRIX-atezolizumab Phase 1/2 trial (NCT02541604) was thus designed to assess the safety and efficacy of Tecentriq across multiple relapsed or refractory tumor types in patients under 30.
The trial had included 87 patients who received at least one dose of Tecentriq, including nine with Hodgkin’s lymphoma and three with non-Hodgkin’s lymphoma. The median age at inclusion was 14, but half the patients were ages 12-18.
Overall, 4.8% of patients responded to treatment, but studies in adults suggest that higher PD-L1 levels are associated with better responses to Tecentriq, which led researchers to test whether the same association existed in younger patients.
Among the 63 patients with available data regarding response and PD-L1 status, 11 had high PD-L1 levels, and 52 had low or no PD-L1 expression in their tumors.
While no responses were seen in the group with low levels, four patients with high PD-L1 levels achieved a partial response to Tecentriq — including two with Hodgkin’s lymphoma and one with non-Hodgkin’s lymphoma. One additional patient had stable disease after treatment.
Despite the low number of patients producing the PD-L1 factor, the findings showed that PD-L1 was significantly associated with a response to Tecentriq.
Researchers also found that lymphoma patients had the greatest proportion of PD-L1-producing tumors and that higher PD-L1 production correlated with increased immune biomarkers. In turn, a higher amount of immune cells within tumors correlated with better responses.
“High PD-L1 expression compared with low or no expression was associated with a greater response to atezolizumab, notably in patients with [Hodgkin’s lymphoma] and [non-Hodgkin’s lymphoma],” researchers concluded. “Despite small sample sizes and limited responses, these biomarker data support adult studies citing the association between PD-L1 and response to atezolizumab; data suggest that PD-L1 may also be a predictor of atezolizumab response in pediatric and young adult patients.”