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PURPOSE The US Food and Drug Administration–expanded access program (EAP) uses a single patient use (SPU) mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade. The aim of this study is to examine the SPU experience for genomically targeted therapies in patients with pediatric cancer. PATIENTS AND METHODS All genomically targeted therapeutic SPUs obtained over a 5-year period were evaluated at four large pediatric cancer programs. Data were collected on the type of neoplasm, agents requested, corresponding molecularly informed targets, and clinical outcomes. RESULTS A total of 45 SPUs in 44 patients were identified. Requests were predominantly made for CNS and solid tumors (84.4%) compared with hematologic malignancies (15.6%). Lack of an available clinical trial was the main reason for SPU initiation (64.4%). The median time from US Food and Drug Administration submission to approval was 3 days (range, 0-12 days) and from Institutional Review Board submission to approval was 5 days (range, 0-50 days). Objective tumor response was seen in 39.5% (15 of 38) of all evaluable SPUs. Disease progression was the primary reason for discontinuation of drug (66.7%) followed by toxicity (13.3%). CONCLUSION SPU requests remain an important mechanism for pediatric access to genomically targeted agents given the limited availability of targeted clinical trials for children with high-risk neoplasms. Furthermore, this subset of SPUs resulted in a substantial number of objective tumor responses. The development of a multi-institutional data registry of SPUs may enable systematic review of toxicity and clinical outcomes and provide evidence-based access to new drugs in rare pediatric cancers.

10012 Background: Circulating tumor DNA (ctDNA) is detectable in children with neuroblastoma. Less is known about how levels change during treatment and the implications of these changes. We evaluated ctDNA pre- and post- 131I-metaiodobenzylguanidine (MIBG) therapy. Methods: We utilized plasma samples from NANT11-01 (NCT02035137), a multi-center, open label, randomized phase II clinical trial evaluating MIBG with or without radiation sensitizers for patients with relapsed or refractory neuroblastoma. Plasma was collected at Baseline prior to MIBG, 72 hours (Hr72), 96 hours (Hr96), 15 days after MIBG (D15), and prior to a second course among patients without progression who received a second course (C2). Samples were analyzed for percent ctDNA levels using ultra-low passage whole genome sequencing. We evaluated associations between ctDNA findings with baseline disease measures of percent involvement in bone marrow, Curie score, and RECIST disease sum of diameters as well as overall response by NANT Response Criteria v1.2 (complete response or partial response coded as responders). Results: Eighty-four patients had a baseline sample and were included in this analysis. Of the 37 patients (44%) with detectable ctDNA at baseline, the median ctDNA level was 32% (range 3.9-91%). Baseline ctDNA levels showed a significant positive correlation with percent involvement in bone marrow (r=0.37; p=0.0004) and Curie score (r=0.26; p = 0.018), but not RECIST sum of diameters for soft tissue sites (r=0.065; p=0.56). Following therapy, the proportions of patients with detectable ctDNA were: Hr72 47% (34/73; median level 28%); Hr96 50% (26/52; median 28%); D15 33% (7/21; median 4%); and C2 14% (3/21; median 50%). Rate of ctDNA detection was similar between responders and non-responders at baseline, Hr72, and Hr96, but lower among responders at D15 and C2 (Table). Among the 21 patients with C2 data, ctDNA levels were either undetectable (n=18) or lower than Cycle 1 Baseline (n=3). Among patients with detectable baseline ctDNA, the median relative ctDNA level at Hr72 (Hr72 ctDNA/baseline ctDNA) for non-responders was 0.87 (n=24) vs. 1.16 for responders (n=7). In contrast, the median relative ctDNA level at C2 for non-responders was 0.56 (n=4) vs. 0 for responders (n=4). Conclusions: ctDNA is detectable in a substantial proportion of patients with relapsed / refractory neuroblastoma, with levels correlated with conventional measures of disease burden. Following MIBG therapy, early timepoints (Hr72 and Hr96) are less informative, whereas ctDNA becomes undetectable at D15 and C2 more commonly in patients with clinical response.[Table: see text]

10044 Background: The sponsor of a clinical trial is the single entity responsible for the overall conduct and oversight of the trial. Sponsors may be pharmaceutical/biotech companies (“industry”), government agencies (e.g. NIH), or other entities such as academic institutions. Trial sponsorship may have important regulatory and financial implications for the trial intervention under investigation. We sought to compare oncology trial sponsorship based upon age of eligibility. Methods: We used the clinicaltrials.gov database to evaluate all interventional trials from September 1, 2009 to December 1, 2018. We included all trials regardless of indication and then separately analyzed only oncology trials. We analyzed sponsor status as “industry”, “government”, or “other”. Results: Sponsorship data were available for 59,582 interventional trials across all disciplines (n = 15,564 oncology trials). Across all disciplines and ages of eligibility, lead trial sponsorship was 34% industry, 5% government, and 61% other. Across all oncology trials, sponsorship mix was similar: 31% industry; 6% government, and 62% other. Among adult oncology trials (age of eligibility starting at age 18 years), trial sponsorship was 33% industry, 6% government, and 61% other. Among pediatric-only oncology trials (age of eligibility capped < 18 years), trial sponsorship was 25% industry, 1% government, and 74% other. 5% of industry sponsored trials across all indications were pediatric-only compared to 0.63% of industry-sponsored trials in oncology. 95% of industry sponsored pediatric-only oncology trials were phase 1 or 2 trials, compared to 90% in adults. Conclusions: Pediatric-only interventional oncology trials are less likely to be industry sponsored compared to adult oncology trials or trials across all disciplines. Less than 1% of industry sponsored interventional trials in oncology focus on children < 18 years of age.

TPS10576 Background: CUDC-907 is an oral first-in-class small molecule inhibitor of histone deacetylases (HDACs) and phosphatidylinositol-3-kinases (PI3Ks), two enzyme classes commonly implicated in pediatric malignancies. Preclinical data demonstrate that inhibition of these enzymes decreases tumor growth across a range of histologies. Data from preclinical and clinical studies suggest that down-regulation of Myc or Mycn signaling may be important in the antineoplastic effects of CUDC-907. Myc or Mycn signaling appears to drive a number of pediatric cancers, heralds a poor prognosis in many of these diseases and has proven difficult to target. CUDC-907 has completed adult phase I testing in patients with hematologic malignancies. The drug was tolerable using a 5 days on/2 days off (5/2) dosing strategy, with a recommended phase II dose of 60 mg. Diarrhea, fatigue, nausea and thrombocytopenia were the most commonly reported side effects. Partial and complete responses were observed in patients with Myc-altered diffuse large B cell lymphoma. Methods: This study is a phase I, open-label, multicenter trial of CUDC-907 in patients 1-21 years of age with relapsed/refractory solid tumors, brain tumors and lymphomas (NCT02909777). The primary objectives are to determine the recommended phase II dose, describe toxicities, and describe pharmacokinetic parameters of CUDC-907 in this population. Other objectives include evaluation of disease response and exploration of the pharmacodynamic effects of CUDC-907. Patients receive CUDC-907 orally on a 5/2 schedule in 28-day cycles, with a pediatric mini-tab formulation available for younger children. Part A consists of a standard 3+3 design evaluating up to three dose levels. Following dose escalation, Part B consists of two expansion cohorts for patients with Mycn/Myc-driven neuroblastoma or mature B-cell lymphoma. Up to 44 patients may be enrolled across Parts A and B. Detailed pharmacokinetic testing is required in the first two cycles. Optional pharmacodynamic testing will quantify histone acetylation, Myc protein, and phospho-S6 in serial blood samples. Enrollment began in October 2016 and is ongoing. Clinical trial information: NCT02909777.