A Phase 1/2 Study of CBX-12 in Children, Adolescents, or Young Adults With Solid Tumors That Have Come Back After Treatment or Are Difficult to Treat

Inclusion Criteria: * PART A: Patients between ≥ 12 months and \< 21 years of age * PART B: Patients between ≥ 12 months and ≤ 30 years of age * Patients with recurrent or refractory extracranial solid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse * Part A: Patients with relapsed or refractory extracranial solid tumors, excluding central nervous system (CNS) * Part B: Patients must have relapsed or refractory rhabdomyosarcoma (B1) or Ewing sarcoma (B2) * PART A: Patients must have either measurable or evaluable disease * PART B: Patients must have measurable disease * Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life * Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age * Patients must have fully recovered (grade \< 2) from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment * Solid tumor patients: ≥ 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/anticancer agents on the COG website * Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): ≥ 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment. * Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1 * Corticosteroids: Patients receiving corticosteroids must be on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid * Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur * Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors) * Stem cell infusions (with or without total body irradiation \[TBI\]): * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: ≥ 84 days after infusion and no evidence of graft versus host disease (GVHD) * Autologous stem cell infusion including boost infusion: ≥ 42 days * Cellular therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) * X-ray therapy (XRT)/external beam irradiation including protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial bone marrow (BM) radiation * Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 \[131I MIBG\]): ≥ 42 days after systemically administered radiopharmaceutical therapy * For patients with solid tumors without known bone marrow involvement: peripheral absolute neutrophil count (ANC) ≥ 1,000/µL * For patients with solid tumors without known bone marrow involvement: platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * For patients with solid tumors without known bone marrow involvement: hemoglobin ≥ 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions) * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity * A creatinine based on age/sex as follows: * Age: 1 to \< 2 years; maximum serum creatinine (mg/dL): 0.6 (male), 0.6 (female) * Age: 2 to \< 6 years; maximum serum creatinine (mg/dL): 0.8 (male), 0.8 (female) * Age: 6 to \< 10 years; maximum serum creatinine (mg/dL): 1 (male), 1 (female) * Age: 10 to \< 13 years; maximum serum creatinine (mg/dL): 1.2 (male), 1.2 (female) * Age: 13 to \< 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female) * Age: ≥ 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female) * A 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 OR a glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) * Note: estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility * Bilirubin (total or sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age, except in patients diagnosed with Gilbert's disease, for whom bilirubin must be ≤ 3.0 × ULN * Alanine aminotransferase (ALT) ≤ 3 x ULN * Aspartate aminotransferase (AST) ≤ 3 x ULN * Albumin ≥ 2 g/dL * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days. If needed, evaluate use of enzyme-inducing anticonvulsants * Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be ≤ grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible * Pulse oximetry \> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest) * Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial Exclusion Criteria: * Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Women of reproductive potential should use effective contraception and should not breastfeed during treatment and for at least 6 months after the last dose of CBX-12. Male patients treated with CBX-12 should use effective contraception and avoid fathering a child during and up to 4 months after treatment * Patients who are currently receiving another investigational drug are not eligible * Patients who are currently receiving other anti-cancer agents are not eligible * Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial * As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 and CYP1A2 (e.g., fluvoxamine) are not eligible. Strong inducers or inhibitors of CYP3A4 and CYP1A2 should be avoided from 14 days prior to enrollment to the end of the study. Enzyme-inducing anticonvulsants: Patients must not have received strong CYP3A4 enzyme-inducing anticonvulsants within 14 days prior to enrollment * Patients must not have received prior exposure to exatecan or deruxtecan based ADCs. Patients with documented progression while on active treatment with a TOP1 inhibitor containing regimen will be excluded * Patients who have an uncontrolled infection are not eligible * Patients who have received a prior solid organ transplantation are not eligible * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible * Patients with known current active CNS primary disease or CNS metastasis whether symptomatic or discovered incidentally without clinical symptoms, are not eligible