PEEL-224 Alone and in Combination with Vincristine and Temozolomide for the Treatment of Refractory, Progressive, or Relapsed Childhood Solid Tumors, Neuroblastoma or Rhabdomyosarcoma

Inclusion Criteria

• PHASE 1: Age ≥ 1 year and ≤ 18 years
• PHASE 2 NBL COHORT: Age ≥ 1 year and ≤ 30 years
• PHASE 2 RMS COHORT: Age ≥ 1 year and ≤ 18 years
• PHASE 1: Refractory, progressive or relapsed non-central nervous system (CNS) solid tumors who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse
• PHASE 2: Refractory, progressive or relapsed neuroblastoma (NBL) or rhabdomyosarcoma (RMS) who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse
• PHASE 1: Evaluable or measurable disease
• PHASE 2: Subjects with NBL: Evaluable or measurable disease by International Neuroblastoma Response Criteria (INRC); subjects with only bone marrow disease are not eligible
• PHASE 2: Subjects with RMS: measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Adequate available archival tumor tissue. Tumor tissue from the most recent biopsy or resection is preferred, if adequate sample is available. If no archival tumor tissue is available, enrollment may be permitted with prior approval by the overall study principal investigator (PI) or designee
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (age ≥ 16 years) or Lansky performance status of at least 60 (age < 16 years)
• Females of childbearing potential must have a negative urine/serum pregnancy test
• PHASE 1 AND PHASE 2: Absolute neutrophil count (ANC) ≥ 750/mm^3 (≥ 7 days since last dose of short acting myeloid growth factor medications [e.g. filgrastim] and ≥ 14 days since last dose of long-acting myeloid medications [e.g. peg-filgrastim]) * Without malignant infiltration of the bone marrow
• PHASE 1 AND PHASE 2: Platelet count ≥ 75,000 mm^3 (≥ 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days) * Without malignant infiltration of the bone marrow
• PHASE 1 AND PHASE 2: Not refractory to packed red blood cell transfusions * Without malignant infiltration of the bone marrow
• PHASE 2: ANC ≥ 500/mm^3 (≥ 7 days since last dose of short acting myeloid growth factor medications [e.g. filgrastim] and ≥ 14 days since last dose of long-acting myeloid medications [e.g. peg-filgrastim]) * Without malignant infiltration of the bone marrow
• PHASE 2: Platelet count ≥ 50,000/mm^3 (≥ 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days) * Without malignant infiltration of the bone marrow
• PHASE 2: Not refractory to packed red blood cell transfusions * Without malignant infiltration of the bone marrow
• PHASE 2: Patients on phase 2 with malignant infiltration of the bone marrow will not be evaluable for hematologic toxicity
• Adequate renal function as evidenced by creatinine clearance as calculated by the Schwartz equation, radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2, or maximum serum creatinine: AGE: 1 to < 2 years: Male 0.6 mg/dL; Female 0.6 mg/dL AGE: 2 to < 6 years: Male 0.8 mg/dL; Female 0.8 mg/dL AGE: 6 to < 10 years: Male 1 mg/dL; Female 1 mg/dL AGE: 10 to < 13 years: Male 1.2 mg/dL; Female 1.2 mg/dL AGE: 13 to < 16 years: Male 1.5 mg/dL; Female 1.4 mg/dL AGE: ≥ 16 years: Male 1.7 mg/dL; Female 1.4 mg/dL * Threshold derived from the Schwartz formula for estimating GFR (Schwartz et al., J.Peds, 106:522,1985) utilizing child length and stature data published by the Center for Disease Control and Prevention (CDC)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT): ≤ 3 times the upper limit of normal (ULN) or ≤ 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the ULN for AST is 50 U/L
• Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT): ≤ 3 times the ULN or ≤ 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the ULN for ALT is 45 U/L
• Total bilirubin: ≤ 1.5 times the upper limit of normal with the exception of patients with Gilbert’s syndrome who must have bilirubin < 3 x institutional ULN
• Prior Therapy: Patients must have had resolution of acute toxic effects of prior therapy to grade ≤ 1 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 except organ function as noted above, adverse events (AE) that are considered clinically non-significant (i.e. alopecia), or controlled on supportive care (i.e. nausea/vomiting, hypothyroidism). Patients must meet the following minimum washout periods prior to enrollment: * Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy * Small molecule targeted therapy: At least 7 days following the last dose of a small molecule targeted agent * Antibody therapy: At least 21 days following the last dose of antibody including anti-GD2 monoclonal antibody * Cellular therapy: At least 42 days following completion of a cellular therapy agent (e.g. modified T cells, natural killer [NK] cells, dendritic cells) * Autologous hematopoietic stem cell transplant and stem cell boost: Subjects must be at least 60 days from day 0 of an autologous stem cell transplant or stem cell boost * Myeloid growth factors: At least 7 days following short-acting myeloid growth factor (e.g. filgrastim) and at least 14 days following the last dose of long-acting myeloid growth factor (e.g. peg-filgrastim) * Thrombopoietin receptor agonists: At least 14 days following last dose of thrombopoietin receptor agonist such as romiplostim * Interleukins, interferons, and cytokines (other than hematopoietic growth factors): At least 21 days following the completion of interleukins, interferon, or cytokines, including interleukin 2 (IL-2) * Radiotherapy: ** At least 14 days after limited field radiation therapy ** At least 90 days after total body irradiation, craniospinal radiotherapy; or radiation to > 50% of pelvis ** At least 42 days must have elapsed if other substantial bone marrow (BM) radiation * Radiopharmaceutical therapy (e.g. radiolabeled antibody, iodine I 131 metaiodobenzylguanidine [131I- MIBG]): At least 42 days after radiopharmaceutical therapy * Major Surgery: At least 2 weeks from prior major surgical procedure. ** Note: Biopsy, CNS shunt placement/revision, and central line placement/removal are not considered major * Strong cytochrome P450 (CYP)1A2 and/or CYP3A4 inhibitors and/or inducers: At least 14 days following use of a strong CYP1A2 and/or CYP3A4 inhibitor and/or inducer. (Note that levofloxacin is permitted when clinically indicated)
• Prior treatment with irinotecan and/or temozolomide is permitted
• Female patients of reproductive potential must agree to use a highly effective contraceptive method for the duration of study therapy and for at least six months after the final dose of PEEL-224. Males of reproductive potential with a female partner of child-bearing potential must use a highly effective for the duration of the study and for at least six months after the final dose of PEEL-224
• Subjects must agree to use sun protective measures while receiving treatment and for 4 weeks after the last dose of PEEL-224
• Parental/guardian permission (informed consent) and if appropriate, child assent

Exclusion Criteria

• Prior treatment with PEEL-224
• Subjects receiving any other anti-cancer agents
• Subjects with primary CNS solid tumors or CNS metastatic disease
• Subjects with prior allogeneic stem cell or solid organ transplantation
• Pregnant or lactating females
• Subjects with a known history of HIV, hepatitis B, and/or hepatitis C (testing not required as part of screening)
• Subjects with symptomatic congestive heart failure