Phase 1b/2 Study of Ifinatamab Deruxtecan in Pediatric Patients with Relapsed or Refractory Solid Tumors (Neuroblastoma, Rhabdomyosarcoma, Wilms Tumor, Osteosarcoma)

The primary objective is to evaluate safety and tolerability and to determine the recommended dose for expansion (RDE) of Ifinatamab Deruxtecan in pediatric participants aged ≥1 month to <12 years with relapsed or refractory solid tumors (excluding primary CNS), thereby establishing a dosing framework and adverse‑event profile for this high‑risk population. Secondary objectives include: assessment of preliminary antitumor activity expressed as overall response rate (ORR) in neuroblastoma, rhabdomyosarcoma and Wilms tumor and DCS‑4 in osteosarcoma; evaluation of duration of response (DOR), disease control rate (DCR), time to response (TTR), and progression‑free survival (PFS) in the same tumor types and ORR in osteosarcoma; determination of overall survival (OS) by tumor type; description of safety and tolerability in each tumor cohort; characterization of the pharmacokinetics (PK) of the ADC and its payload DXd; and assessment of immunogenicity of the investigational product.

The study enrolled 52 participants, encompassing both male and female children, with ages ranging from ≥1 month to <12 years for the initial cohort and up to <18 years for the subsequent cohort. All enrolled individuals had relapsed, refractory solid tumors (excluding primary CNS involvement) and demonstrated radiological disease progression after at least one line of prior therapy in the locally advanced or metastatic setting, with no satisfactory alternative treatment options. Selection criteria required a histologically confirmed diagnosis of osteosarcoma, neuroblastoma, rhabdomyosarcoma, or Wilms tumor for the later cohort, while the earlier cohort accepted any solid tumor meeting the progression criteria. Participants were required to have recovered from adverse events related to previous anticancer therapies to ≤Grade 1, or to have endocrine‑related adverse events controlled with hormone replacement, ≤Grade 2 neuropathy, or ≤Grade 2 alopecia. The overall health status of the cohort was characterized by advanced disease without other comorbid conditions that would preclude study participation. The investigational agent evaluated was ifinatamab deruxtecan in this pediatric population.

The substudy is an integrated Phase 1b/2 trial evaluating the safety, tolerability, recommended dose for expansion, and preliminary antitumor activity of Ifinatamab Deruxtecan in pediatric participants with relapsed or refractory solid tumors, a subset of malignant neoplasm. The study consists of two parts: Part 1 enrolls children ≥1 month to <12 years with any relapsed/refractory solid tumor (excluding primary CNS); Part 2 enrolls participants ≥1 month to <18 years with histologically confirmed osteosarcoma, neuroblastoma, rhabdomyosarcoma, or Wilms tumor who have progressed after at least one prior therapy. After obtaining informed consent/assent, participants undergo a screening visit to confirm eligibility, including radiologic disease progression and recovery from prior therapy‑related adverse events to ≤Grade 1 (or ≤Grade 2 for specific toxicities). Eligible participants then receive an initial infusion of the investigational product followed by scheduled follow‑up visits every 3 weeks for safety assessments, dose modifications, and pharmacokinetic sampling; tumor assessments are performed every 8 weeks to determine objective response rate and disease control success at 4 months. The trial continues until disease progression, unacceptable toxicity, withdrawal of consent, or completion of the predefined treatment period, after which an end‑of‑study visit records final outcomes. Participant involvement may extend for several treatment cycles, typically up to 12 months, but may be terminated early for dose‑limiting toxicities, serious adverse events, or protocol non‑compliance. Recruitment began in July 2026 and is planned to conclude in August 2031.

The investigational product is Ifinatamab Deruxtecan, supplied as a solution for infusion for administration by intravenous infusion. The specific dose, dose unit, and frequency of administration are defined in the study protocol and are adjusted according to the participant’s age, body weight, and clinical status; dosing intervals are typically based on a repeat‑dose schedule outlined in the protocol.

No additional investigational agents are administered in this study. Participants may receive concomitant standard‑of‑care therapies, supportive measures, or rescue medications at the discretion of the treating investigator, provided these are documented and do not interfere with the evaluation of the investigational product. Drug administration is performed by qualified clinical staff, and compliance with the dosing schedule is monitored through infusion records, source documentation, and periodic review of treatment logs.

Efficacy will be evaluated using tumor‑specific response parameters, including Objective Response Rate for participants with neuroblastoma, rhabdomyosarcoma, and Wilms tumor, Disease Control Success at 4 months (DCS‑4) for osteosarcoma, as well as secondary measures such as Duration of Response, Disease Control Rate, Time to Response, Progression‑free Survival, and Overall Survival.

Assessments will be performed by the investigator according to tumor type. Disease control will be recorded at the 4‑month timepoint for DCS‑4, and all response evaluations will be conducted at baseline and at predefined intervals throughout treatment. Radiographic or other appropriate imaging modalities will be used to determine tumor response, and the results will be analyzed according to standard criteria for each endpoint.