About

Frank Milton Balis, M.D., is a Professor of Pediatrics (Oncology) at the Children's Hospital of Philadelphia. He holds the Louis and Amelia Canuso Family Endowed Chair for Clinical Research in Oncology at the same institution. Dr. Balis is also a Co-Leader of the Clinical Pharmacology Research Affinity Group at the Children's Hospital of Philadelphia. His clinical expertise focuses on solid tumors in children, renal tumors in children, and the clinical pharmacology of anticancer drugs. His research expertise includes clinical pharmacology of anticancer drugs, cancer biomarkers, and clinical trial design. Dr. Balis has contributed to the field through various research projects and publications related to pediatric oncology and pharmacology.

Research topics

• Medicine
• Internal medicine
• Oncology
• Biology
• Genetics

Selected publications

• A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric and Young Adult Solid Tumors

  Pediatric Blood & Cancer · 2025-05-01 · 1 citations

  articleOpen access

  INTRODUCTION: Developing targeted therapies with manageable toxicities remains a high priority for pediatric cancer. We sought to determine the recommended Phase 2 dose (RP2D) and evaluate the antitumor activity of lenvatinib+everolimus in children/young adults with select recurrent/refractory solid tumors. METHODS: Patients 2-21 years old were eligible. Phase 1 used a rolling-six design. Phase 2 was limited to patients with Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), or high-grade glioma (HGG), and ≤2 prior VEGF/VEGFR-targeted therapies. Primary endpoints included the determination of maximum tolerated dose (MTD), RP2D, safety/toxicity (Phase 1), and objective response rate (ORR) per RECIST version 1.1 (RANO for HGG) at Week 16 (Phase 2). RESULTS: orally once daily. DL1 was declared the MTD/RP2D given dose-limiting toxicities (proteinuria [n = 1]; hypertriglyceridemia and hypercholesterolemia [n = 1]) observed in two of 12 patients treated at DL1. In Phase 2, 41 patients (EWS, n = 10; RMS, n = 20; HGG, n = 11) were treated with the RP2D. Two patients with RMS experienced partial response by Week 16. No other objective responses were observed. Two patients with EWS experienced prolonged disease control (≥23 weeks). No new safety signals were identified. The safety profile was similar to those of treated adults with renal cell carcinoma. CONCLUSION: Lenvatinib+everolimus has a manageable safety profile in this pediatric population. Despite unmet efficacy endpoints, the antitumor activity observed in RMS and EWS may warrant further study in select pediatric solid tumors. GOV NUMBER: NCT03245151.

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• Abstract B001: Phase 1/2 trial to evaluate the safety and efficacy of PEEL-224 in combination with vincristine and temozolomide in adolescents and young adults with relapsed or refractory sarcomas

  Molecular Cancer Therapeutics · 2025-10-22

  article

  Abstract BACKGROUND: Sarcomas affecting adolescents and young adults, including Ewing sarcoma (EWS), desmoplastic small round cell tumor (DSRCT), rhabdomyosarcoma (RMS) and osteosarcoma (OS), cause significant disease and treatment related morbidity and mortality. Conventional topoisomerase 1 (TOP1) inhibitors like irinotecan are active agents in each of these diseases but have numerous shortcomings including poor bioavailability, susceptibility to resistance and often intractable diarrhea. PEEL-224 is a tetravalent, pegylated, pro-drug of SN22, a pharmacologically enhanced TOP1 inhibitor. PEEL-224 is water-soluble, does not require hepatic activation, and has a prolonged half-life, allowing for increased drug delivery to tumor and once weekly dosing. SN22 does not undergo glucuronidation and ABC transporter-mediated cellular export, thereby reducing acquired resistance. The lack of glucuronidation and anticholinergic activity reduces GI toxicity. Pre-clinical data in EWS, DSRCT and RMS mouse models demonstrate significantly improved efficacy over irinotecan. METHODS: This prospective, open-label, single-arm, non-randomized, phase 1/2 clinical trial is the first to assess PEEL-224 in combination with other agents. Sites will be Dana-Farber Cancer Institute, Children’s Hospital of Philadelphia, UCSF, and MD Anderson Cancer Center. Patients 12-49 years of age with relapsed or refractory sarcomas receive PEEL-224 (days 1,8) in 21-day cycles in combination with vincristine (days 1,8) and oral temozolomide [days 1-5; V(P)T]. The phase 1 dose escalation portion of the trial is designed to determine the recommended phase 2 dose of PEEL-224 given in combination with vincristine and temozolomide. During phase 2, there are two dedicated cohorts for patients with relapsed or refractory EWS and DSRCT designed to determine the objective response rate to V(P)T. In each cohort, patients will be required to have measurable disease by RECIST v1.1. A third expansion cohort for patients with “other” sarcomas will estimate progression-free survival in patients treated with V(P)T. Phase 1 includes limited pharmacokinetic profiling of PEEL-224 and free SN22 since PEEL-224 has not been given on a three-week schedule previously. Phase 1 and 2 include tumor sequencing and ctDNA analysis to assess ctDNA burden over time as well as genomic markers of sensitivity and resistance. The trial is now open and enrolling (NCT06709495). Citation Format: David S. Shulman, Alexandra Sala, Ketki Bhushan, Emily Blair, Jeanine M. McManus, Kerri L. Cavanaugh, Julia H. Garland, Rebecca Divirgilio, Sarah Sexton, Julie P. Field, Sarah Garcia, Susan Carrozza, Melissa B. Hohos, Mary M. Murphy, Michael J. Wagner, Jacquelyn Crane, Amit Sabnis, Jennifer Michlitsch, Theodore Laetsch, J Andrew. Livingston, Jonathan B. Gill, Nan Chen, Kelly Klega, Catherine Clinton, Brian D. Crompton, Frank M. Balis, Wendy B. London, Steven G. DuBois. Phase 1/2 trial to evaluate the safety and efficacy of PEEL-224 in combination with vincristine and temozolomide in adolescents and young adults with relapsed or refractory sarcomas [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B001.

  PublisherDOI

• New approach to busulfan dosing in infants and children based on a population pharmacokinetic analysis

  Cancer Chemotherapy and Pharmacology · 2025-02-11

  articleOpen access1st authorCorresponding

  Abstract Purpose Apply population pharmacokinetic modeling to a single institution busulfan therapeutic drug monitoring (TDM) data set from infants and children to refine dosing methods. Methods One-compartment pharmacokinetic model was fit to busulfan TDM data from 328 infants and children with malignant and non-malignant diseases treated with busulfan-containing transplant conditioning regimens. Age-dependence of busulfan clearance scaled to body weight and body surface area (BSA) was compared, and busulfan AUC was simulated for a BSA-scaled dose of 100 mg/m 2 combined with a BSA-banded dosing table for infants and children with a BSA < 0.5 m 2 . Results Busulfan clearance scaled to body weight is age-dependent. Clearance in children ≤ 3 years (0.234 L/[h•kg]) is higher than the typical value for the population, (0.205 L/[h•kg]), and 48% of children < 5 years have subtherapeutic busulfan AUCs after the first dose. Busulfan clearance scaled to BSA (typical value, 5.47 L/[h•m 2 ]) is more uniform across the pediatric age span, except for infants (≤ 1 year, 4.27 L/[h•m 2 ]). Simulated busulfan AUCs with a dose of 100 mg/m 2 for patients with a BSA ≥ 0.5 m 2 combined with a BSA-banded dosing table for patients with a BSA < 0.5 m 2 achieved a therapeutic AUC after the first dose in 49% more patients than body weight scaled doses. Conclusion Our model predicts a greater proportion of children would achieve a therapeutic busulfan AUC after the first dose with a dose of 100 mg/m 2 /d combined with the infant dosing table for patients with a BSA < 0.5 m 2 compared to body weight-scaled dosing.

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• Wilms Tumor, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology

  Journal of the National Comprehensive Cancer Network · 2025-08-01 · 3 citations

  article1st authorCorresponding

  The NCCN Clinical Practice Guidelines (NCCN Guidelines) for Wilms Tumor (WT; nephroblastoma) cover strategies for the screening, diagnosis, and treatment of WT, which is the most frequent primary kidney tumor in children. WT can generally be separated into 2 histology types: favorable histology WT and anaplastic WT. Five-year survival is high for children with favorable histology WT who receive appropriate treatment; however, survival rates are much lower for patients who present with higher stage diffuse anaplastic WT. Treatment of WT can range from surgery alone to surgery plus intensive chemotherapy and radiation depending on whether the tumor is unilateral or bilateral, histology, and local stage. The goal of therapy is to maximize cure while minimizing long-term toxicities. The content featured in this issue covers the NCCN panel's recommendations for overall management of both favorable histology WT and anaplastic WT.

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• Anti‐Tumor Activity of Paclitaxel‐Containing Regimens in Recurrent/Refractory Wilms Tumor

  Pediatric Blood & Cancer · 2025-07-25 · 3 citations

  article

  BACKGROUND: The Pediatric Oncology Group P9262 Phase 2 study of single-agent paclitaxel demonstrated one complete response (CR), one partial response (PR), and four with stable disease (SD) among 15 patients with recurrent Wilms tumor (WT). Based on this activity, paclitaxel-containing regimens have been used as salvage therapy for treatment-refractory WT. We conducted a multi-institutional retrospective study to further characterize the clinical activity of paclitaxel-containing regimens in recurrent WT. METHODS: Twelve institutions submitted anonymized data from patients with relapsed WT treated with paclitaxel. Response after one or two cycles of a paclitaxel-containing regimen was reported according to Response Evaluation Criteria in Solid Tumors. RESULTS: Twenty-eight patients with a median age at diagnosis of 5.5 years (range: 3 months to 31.9 years) were reported. Twenty had non-anaplastic WT; eight had diffuse anaplasia (DA). Stage at diagnosis was I (n = 1), II (n = 1), III (n = 11), IV (n = 14), and V (n = 1). Patients received a mean of 8.5 anticancer drugs (range: 6-12) before paclitaxel, including eight who received high-dose therapy/stem cell transplant. Paclitaxel (n = 13) or nab-paclitaxel (n = 15) were predominantly administered in combination with other agents, most commonly doxorubicin and/or gemcitabine. Eleven of 26 patients with measurable disease had a partial response (7 = non-anaplastic; 4 = DA), four had stable disease, and 11 had progressive disease. Two patients without measurable disease maintained a complete response for 12 and 16 months. The mean duration without progression was 7.6 months (range: 1-35 months). CONCLUSIONS: Paclitaxel-containing regimens appear to be active against heavily pretreated WT with either non-anaplastic or DA histology. Prospective studies are warranted to formally evaluate the efficacy of paclitaxel-based therapies.

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• Alternative mRNA splicing in anthracycline-induced cardiomyopathy – a COG-ALTE03N1 report

  Cardio-Oncology · 2025-05-17 · 2 citations

  articleOpen access

  Abstract Background Anthracycline-induced cardiomyopathy is a well-established adverse consequence in childhood cancer survivors. Altered mRNA expression in the peripheral blood has been found at the level of genes and pathways among anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. However, the role of aberrant alternative splicing in anthracycline-induced cardiomyopathy remains unexplored. The present study examined if transcript-specific events, due to alternative splicing occur in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Methods Participants were anthracycline-exposed childhood cancer survivors with cardiomyopathy (cases) matched with anthracycline-exposed childhood cancer survivors without cardiomyopathy (controls; matched on primary cancer diagnosis, year of diagnosis, and race/ethnicity). mRNA sequencing was performed on total RNA from peripheral blood in 32 cases and 32 matched controls. Event-level splicing tool, rMATS (replicate Multivariate Analysis of Transcript Splicing) was used for quantitative profiling of alternative splicing events. Results A total of 45 alternative splicing events in 36 genes were identified. Using a prioritization strategy to filter the alternative splicing events, intron retention in RPS24 and skipped exon of PFND5 showed differential expression of altered transcripts. Conclusions We identified specific alternative splicing events in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Our findings suggest that differential alternative splicing events can provide additional insight into the peripheral blood transcriptomic landscape of anthracycline-induced cardiomyopathy. Graphical abstract Central Illustration. Aberrant alternative splicing and anthracycline-induced cardiomyopathy. This study sought to identify alternative splice variants that are differentially abundant between anthracycline-exposed childhood cancer survivors that developed cardiomyopathy (cases) versus those who did not (controls). We observed dysregulated alternative splicing of PFDN5 and RPS24 is associated with the development of cardiomyopathy.Splicing defects in PFDN5 impair cytoskeletal protein folding, while RPS24 dysregulation affects their translation, disrupting actin and tubulin homeostasis. Together, these alterations destabilize cardiomyocyte structure, contributing to sarcomere disorganization and the development of cardiomyopathy. Created in BioRender. Singh, P. (2025) https://BioRender.com/59zmgls .

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• Circulating Free and Low-Density Lipoprotein-Bound GD2 Can Compete with Neuroblastoma Cells for Binding Therapeutic Anti-GD2 Antibodies

  2025-04-22

  preprintOpen accessSenior author

  Background: GD2 is a ganglioside that is expressed on the surface of neuroblastoma cells and shed into the circulation, where it primarily circulates bound to low density lipoprotein (LDL). We questioned whether free GD2 or GD2 bound to LDL could interfere with the binding of therapeutic anti-GD2 monoclonal antibodies like dinutuximab to neuroblastoma cells. Procedure: The GD2-expressing neuroblastoma cell line IMR5 was stained with an anti-GD2 antibody tagged with allophycocyanin (APC) at the lowest possible saturating concentration, and median fluorescence intensity was measured by flow cytometry after in vitro exposure to free GD2 or GD2 bound to LDL at concentrations of 0nM, 100nM, 1μM, and 5μM. Control experiments assessed the ability of cells with GD2 surface-expressed and GD2-non-expressing cells to compete for anti-GD2-APC antibodies with a population of 2 million IMR5 cells. Results: Free and LDL-bound GD2 reduced the binding of anti-GD2-APC antibodies to IMR5 cells in vitro in a concentration-dependent manner. At 100nM, which is below the median plasma GD2 concentration measured in patients with high-risk neuroblastoma prior to therapy, reduced antibody binding to IMR5 cells by 40%. Conclusions: At physiologic concentrations found in the plasma of patients with high-risk neuroblastoma, free GD2 and LDL-bound GD2 reduced the binding of anti-GD2 antibodies to GD2-expressing neuroblastoma cells, in vitro . This suggests that circulating GD2 could impact the efficacy of therapeutic anti-GD2 antibodies administered to patients with a high disease burden during induction therapy or at relapse.

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• A Phase 1 Trial of Fimepinostat in Children and Adolescents With Relapsed and Refractory Solid and <scp>CNS</scp> Tumors

  Cancer Medicine · 2025-11-27 · 4 citations

  articleOpen access

  ABSTRACT Background Fimepinostat, an oral dual inhibitor of histone deacetylase (HDAC) and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K), has shown activity in preclinical models of Myc‐driven pediatric malignancies. This Phase 1 trial aimed to determine the recommended pediatric Phase 2 dose (RPP2D), describe the toxicity profile, and evaluate the pharmacokinetics of fimepinostat in children with relapsed and refractory solid and central nervous system (CNS) tumors. Methods This multicenter, Phase 1 study enrolled patients ages 1–21 years with relapsed or refractory solid tumors, CNS tumors, or lymphoma. The dose‐escalation phase followed a 3 + 3 design, starting at 27.5 mg/m 2 and escalating to 45 mg/m 2 . Following dose escalation, three expansion cohorts were opened including cohorts for patients with Myc(n)‐driven neuroblastoma, Myc‐driven extracranial solid tumors, and diffuse large B‐cell lymphoma or Burkitt lymphoma. The pharmacokinetics of fimepinostat and its metabolites were studied after the first dose. Results Twenty‐six patients were enrolled, with 25 receiving treatment. The median age was 13.6 years (range: 4.1–20.9). In the dose‐escalation phase, 12 patients were evaluable for DLT assessment. The RPP2D was initially determined to be 45 mg/m 2 but was revised to 35 mg/m 2 after observing DLTs in the dose‐expansion phase. Treatment‐related adverse events were primarily hematologic and gastrointestinal. No objective responses were observed in 23 evaluable patients. Three patients had stable disease for over four cycles, including a patient with MYCN amplified neuroblastoma with stable disease for 24 cycles. Pharmacokinetic analysis showed significant interpatient variability and rapid conversion of fimepinostat to its metabolites. Conclusion Fimepinostat was tolerable at a dose of 35 mg/m 2 in children with relapsed and refractory solid and CNS tumors, but lacked significant clinical activity. Discovery of drugs to target Myc continues to be a high priority for childhood cancers. Trial Registration ClinicalTrials.gov identifier: NCT02909777

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• Infantile Fibrosarcoma of the Hand: Limb-Sparing Treatment With Modern Targeted Oral Chemotherapy and Conservative Surgical Resection

  Journal of Hand Surgery Global Online · 2025-12-05

  articleOpen access

  fusion oncogenes have been used to decrease the extent of surgical resection. However, the management of morphologically similar infantile fibrosarcoma-like tumors has not been well characterized. We report a case of an anaplastic lymphoma kinase-driven infantile fibrosarcoma-like neoplasm of the hand that was managed using a multimodal, limb-sparing approach. A 35-week gestation neonate presented with a vascular mass on the volar aspect of his left hand. Neoadjuvant treatment with the anaplastic lymphoma kinase inhibitor lorlatinib led to considerable tumor regression, which enabled conservative surgical resection and preservation of the hand. At 2 years of follow-up, the patient remains on lorlatinib therapy without recurrence and demonstrates excellent hand function despite moderate scar contractures. This case highlights the efficacy of neoadjuvant therapy combined with resection in managing infantile fibrosarcoma-like tumors.

  PublisherDOI

• Complex pediatric neoplasms: The role of congenital cardiothoracic surgery

  JTCVS Techniques · 2025-02-08

  articleOpen access

  Background: Surgery for pediatric solid neoplasms is often complicated by local tumor invasion. Cardiac surgeons can provide expertise in the chest and facilitate potentially aggressive management of tumors invading vasculature, pericardiac, or diaphragmatic spaces. Here we present 4 complex cases. Methods: This descriptive retrospective chart review study included 4 surgical patients with locally invasive solid tumors. Results: Case 1: 16 × 15.5 × 11 cm right chest synovial sarcoma in a male patient status post-neoadjuvant chemoradiation. Imaging revealed invasion of the right-sided subclavian vein, subclavian artery, phrenic nerve, and vagus nerve. The surgical approach via hemi-clamshell allowed for R0 resection. Case 2: Resection of a 17.6 × 10.5 × 8.1 cm sclerosing epithelioid fibrosarcoma originating from the vertebral body but causing aortic arch, right and left pulmonary artery, tracheal, and esophageal displacement. The surgeons preserved nearly all thoracic anatomy despite extensive periaortic and posterior mediastinal dissection. Case 3: Synchronous removal of a 11.5 × 9 × 5.5 cm pleuropulmonary blastoma at the time of tetralogy of Fallot repair. Case 4: Resection of a 12 × 0.5 × 0.3 cm nonviable Wilms tumor traversing from the right renal vein to the level of the Eustachian valve. All patients were extubated in the operating room and had an uneventful hospital course, with length of stay ranging from 5 to 10 days. Conclusions: Pediatric patients may present with locally advanced heterogenous neoplasms. The added anatomic familiarity with the mediastinum, thoracic hilum, and great vessels in particular ensured safe resection in all cases. Thus, cardiothoracic surgery consultation is valuable when managing complex thoracic oncologic tumor resection.

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Recent grants

• NIH Grant Z01SC006880

  NIH · $3.6M

• NIH Grant ZIABC011080

  NIH · $1.3M

• NIH Grant ZIASC006880

  NIH · $1.1M

• NIH Grant Z01BC011080

  NIH · $1.2M

Frequent coauthors

• Elizabeth Fox

  452 shared

• Peter C. Adamson

  Sanofi (United States)

  384 shared

• Brigitte C. Widemann

  National Cancer Institute

  353 shared

• Susan M. Blaney

  Children's Cancer Center

  322 shared

• David G. Poplack

  Texas Children's Hospital

  207 shared

• Ashish M. Ingle

  138 shared

• Seth M. Steinberg

  Office of the Director

  138 shared

• Stacey L. Berg

  Mayo Clinic

  132 shared

Education

• MD, Medicine

  Vanderbilt University School of Medicine

  1975

• BS, Zoology

  University of North Carolina at Chapel Hill

  1971

Awards & honors

• The Louis and Amelia Canuso Family Endowed Chair for Clinica…