iMATRIX-Atezolizumab, a Phase 1/2 Study of the Safety, Pharmacokinetics, and Activity of Atezolizumab in Paediatric/Young Adult Patients with Previously Treated Solid Tumours

Background: Atezolizumab targets programmed death-ligand 1 (PD-L1), leading to enhanced anticancer T-cell activity. The iMATRIX-atezolizumab study (phase 1/2, multicentre, open-label; NCT02541604) is the first trial to evaluate the safety, pharmacokinetics, and activity of atezolizumab in paediatric/young adult patients with refractory/relapsed solid tumours, with known or expected PD-L1 expression. Methods: Patients received atezolizumab on day 1 of each 3-week cycle until disease progression (PD)/loss of clinical benefit. Patients <18 years old received 15 mg/kg atezolizumab (maximum dose 1200 mg). Patients ≥18 to <30 years old received the adult dose of 1200 mg atezolizumab. Findings: Ninety patients (median age 14 years [range, 0-29]) with various solid tumours and lymphomas were enrolled. At the data cut, two patients remained on study treatment. The most frequently reported adverse events (AEs) included pyrexia (41·4%) and fatigue (35·6%). Fifty-seven patients (65·5%) experienced treatment-related AEs (grade 1-4). Atezolizumab exposure in patients aged 2 to <18 years was generally similar to exposures in young adults (≥18 years) and was above the target exposure in all patients. At 6 months, as best overall response, four patients (4.6%) showed a partial response (PR) and 11 patients (12·6%) showed stable disease (SD). Among the 63 patients with both treatment response and PD-L1 expression data, all four patients exhibiting high PD-L1 expression had PR; the other seven with high baseline PD-L1 expression exhibited SD (n=1) or PD (n=6). Interpretation: The observed safety and pharmacokinetic profile of atezolizumab was similar to that observed in adults. Atezolizumab activity was low. These data may help to inform future development of checkpoint inhibitors as monotherapy in defined populations or in combination in paediatric/young adult populations. Clinical Trial Registry: NCT02541604 Funding Statement: This study was funded by F. Hoffmann-La Roche Ltd. Declaration of Interests: BG reports attendance at a Roche-sponsored advisory board for atezolizumab. JM, NC and FB have nothing to disclose. MC reports personal fees from Bayer, Lilly, Roche, Servier, and Tesaro outside the submitted work. CMZ reports grants from Pfizer, Jazz Pharma, and Celgene; and personal fees from Novartis outside the submitted work. LVM reports personal fees from Tesaro outside the submitted work. FD, HC, MFK and GR are employed by Roche. ML, KEH, and CS are employed by Genentech. TT reports relevant financial activities outside of the submitted work from Roche/Genentech. Ethics Approval Statement: The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice, and approved by the Institutional Review Board/Ethics Committee according to local law and regulations in each participating country. Informed consent was received from all study participants.