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FDA Panel Endorses Early Trials of Promising Anticancer Agents in Pediatric Patients

Jason M. Broderick @jasoncology
Published: Wednesday, Jun 29, 2016

Alberto S. Pappo, MD

Alberto S. Pappo, MD

Members of the Pediatric Subcommittee of the FDA’s Oncologic Drugs Advisory Committee (pedsODAC) voiced their support for new clinical trials examining promising cancer agents in pediatric patients.

During a 2-day meeting,1,2 the panel heard representatives from 5 pharmaceutical companies discuss ongoing or planned early stage pediatric trials exploring atezolizumab (Genentech), LOXO-101 (Loxo Oncology), entrectinib (Ignyta), venetoclax (AbbVie/Genentech), and tazemetostat (Epizyme). The panelists reacted favorably to the companies’ presentations, supporting each of the 5 pediatric development plans.


The FDA granted the PD-L1 inhibitor atezolizumab (Tecentriq) an accelerated approval as a treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery.

The approval was based on data from the phase II IMvigor 210 study, in which atezolizumab had an overall response rate (ORR) of 14.8% in patients with locally advanced or mUC, regardless of PD-L1 expression. Among patients with PD-L1 expression ≥5%, ORR was 26%.

Several pediatric tumors have been observed to express PD-L1, including high-grade gliomas, rhabdomyosarcoma, lymphomas, soft tissue sarcomas, osteosarcoma, Ewing sarcoma, neuroblastoma, and Wilms tumor. Pediatric tumors have also been shown to have CD8+ tumor-infiltrating lymphocytes.

Through its iMATRIX trial platform, Genentech is collaborating with several pediatric oncology cooperatives to initiate clinical trials examining several potential treatments, including atezolizumab, in pediatric patients. The company’s current plan for atezolizumab in the pediatric setting consists of a nonclinical biomarker analysis and a clinical study.

The biomarker study is examining PD-L1 expression, the presence of CD8+ T cells, and other immune markers in 100 pediatrics tumor samples from patients with a variety of tumor types. The first clinical trial, study G029664, is accruing 40 to 100 pediatric and young adult patients aged <30 years with relapsed or refractory neuroblastoma, rhabdomyosarcoma, non- rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, Hodgkin lymphoma, or non-Hodgkin lymphoma. Patients with other tumor types also have the potential to enroll.

The ongoing, open-label, multicenter single-arm study is designed to evaluate the safety and preliminary efficacy of atezolizumab in these patients. Most of the patients enrolled will have known PD-L1 expression; however, a limited number of patients who do not have documented PD-L1 expression will also be allowed to participate.

Patients <18 years of age will receive atezolizumab at 15 mg/kg (maximum 1200 mg) and patients aged ≥18 years will receive 1200 mg. The treatment will be administered every 3 weeks. After at least 10 patients for a specific tumor type have been treated and followed up for at least 6 months, Genentech will determine whether to enroll an expansion cohort with up to 40 patients. Depending on the results of an individual expansion cohort, the company will then decide whether to launch a second study to further examine atezolizumab in that tumor type.

“Overall, the committee feels that the study design is on target—it’s a classic phase I/II,” Alberto S. Pappo, MD, chairperson of pedsODAC, said when summarizing the panel’s response to the Genentech presentation.

Addressing the Genentech representative, Pappo added, “You should also consider combination studies, and those should be done relatively quickly once you’ve identified a dose and a subset of patients who may benefit from this drug. Also, there may not be a very clear correlation between histology and response in pediatric tumors, and therefore, you should explore immune competence, age, and other factors to better assess the reason for a response in these patients.”

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