Relapsed / Refractory Osteosarcoma
Conditions
Brief summary
This is a multi-center, non-randomized, open-label, dosimetry and dose-escalation, cohort-expansion study of LNTH-2403 administered to subjects with relapsed / refractory (R/R) osteosarcoma. This study consists of 2 phases: (1) a dosimetry and dose escalation phase; and (2) a cohort expansion phase.
Interventions
DRUGLNTH2403 Phase 1 dose
LNTH-2403 administered once every 8 weeks, with the potential to explore other dosing schedules based on observed radiation dosimetry and PK parameters and safety and tolerability data.
DRUGPhase 2; LNTH2403 a single agent recommended phase 2 dose (RP2D).
Once the RP2D is selected, phase 2 will commence
Sponsors
Lantheus Medical Imaging
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 will evaluate escalating doses of LNTH-2403 administered once every 8 weeks, with the potential to explore other dosing schedules based on observed radiation dosimetry and PK parameters and safety and tolerability data. Phase 2 will evaluate LNTH-2403 as a single agent in participants with R/R osteosarcoma at the recommended phase 2 dose (RP2D).
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all the following criteria to be enrolled in the study 1. Histopathologic documented diagnosis of R/R osteosarcoma 2. Must have disease characterized by at least one of the following (Participants meeting only (b.), only (c.), or only (b. and c.) must be discussed with and receive written approval from the Sponsor to qualify). 1. Measurable as defined in RECIST 1.1 2. Evaluable non-measurable disease as per RECIST 1.1 3. Bone only without a soft tissue component: must be 18F-FDG-PET avid and evaluable by serial 18F-FDG-PET imaging studies. 3. Age: a. First Cohort in Phase 1: ≥ 18 years-of-age at the time of signature of the main study ICF. b. Second and subsequent cohorts, in Phase 1 and all participants in Phase 2: ≥12years-of-age at the time of signature of the main ICF. 4. Performance Status: 1. Eastern Cooperative Oncology Group (ECOG) Performance Score (PS): 0 - 2 2. Lansky PS ≥ 50. 5. Body weight: ≥ 30 kg. 6. Tumor biopsies; Fresh or Archival 7. Progression following at least one course of chemotherapy, which includes neoadjuvant / perioperative systemic therapy. 8. All adverse events (AEs) related to prior therapies (chemotherapy / systemic therapies, radiation, surgery) must have resolved to Grade 1 or baseline 9. Organ Function 10. Pregnancy Women of Child-Bearing Potential (WOCBP) must have a negative serum pregnancy test result at screening 11. Contraception- Male participants with a WOCBP partner must use 2 forms of acceptable contraception 12. Written informed consent and/or assent must be obtained according to local guidelines and signed and dated by the participant, parent, and/or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
Exclusion criteria
Participants meeting any of the following criteria will be excluded from the study 1. Known allergies, hypersensitivity, or intolerance to LNTH-2403 and/or its excipients 2. Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, may affect the participant's safety, compliance with the study, or otherwise impair the assessment of study results 3. Concurrent treatment with any other anti-neoplastic agents, including localized radiation therapy 4. Known active infection 5. Participation in an interventional study of another investigational agent 6. Prior therapies or diagnostics 7. Active prior or concurrent malignancy: immunoglobulin), 8. Known active liver disease from any cause, Hepatitis A Virus 9. Known to be human immunodeficiency virus (HIV) positive 10. Clinically relevant cardiovascular disease 11. Receipt of live vaccine within the 30 days prior to the first dose o 12. A female participant who is pregnant or breastfeeding 13. Major surgical procedure within 28 days of the first dose of LNTH-2403. 14. Participant is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To identify the maximum tolerated dose (MTD) of LNTH-2403 in participants with R/R osteosarcoma (Ph1) | From enrollment to the end of treatment at 8 weeks | Incidence of DLTs during the first 8 weeks (DLT evaluation window) after the first dose of LNTH-2403 |
| To evaluate the safety and tolerability profile of LNTH-2403 in participants with R/R osteosarcoma (Ph1) | From enrollment to the end of treatment at 8 weeks | Type, frequency, severity, timing, and relationship to LNTH-2403 of all Treatment-emergent adverse event, (TEAEs) and Serious adverse events, (SAEs) |
| To assess the preliminary anti-neoplastic activity of LNTH-2403 in participants with R/R osteosarcoma (Ph2) | From enrollment to Event-Free Survival (EFS) at 4 months | Event-Free Survival (EFS) at 4 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the preliminary anti-neoplastic activity of LNTH-2403 in participants with R/R osteosarcoma (Ph1) | 8 weeks | Event-Free Survival (EFS) at 8 weeks |
| To describe the safety and tolerability profile of LNTH-2403 in participants with R/R osteosarcoma (Ph2) | 4 months | Type, frequency, severity, timing, and relationship to LNTH-2403 of any TEAEs and SAEs |
Countries
United States
Contacts
CONTACTKerri Sforzo
Outcome results
None listed