Phase 2
N=26
Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors
Recurrent Malignant Solid Neoplasm · Recurrent Osteosarcoma · Refractory Malignant Solid Neoplasm · Refractory Osteosarcoma
Bottom Line
View on ClinicalTrials.gov: NCT03320330 ↗Enrolled (actual)
26
Serious AEs
69.2%
Results posted
Apr 2022
Primary outcome: Primary: Number of Participants With Dose Limiting Toxicities — 0; 0; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Laboratory Biomarker Analysis (Other); Pepinemab (Biological); Pharmacological Study (Other)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Dec 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities |
0; 0; 1 | — |
| PRIMARY Patients Who Had Grade 3 or Above Toxicities With the Three Attributions, 'DEFINITE', 'POSSIBLE','PROBABLE' |
0; 1; 3 | — |
| PRIMARY Half-life |
281; 221; 162 | — |
| PRIMARY Time to Maximum Concentration (T Max) |
1.9; 1.7; 1.7 | — |
| PRIMARY Maximum Concentration (C Max) |
175; 203; 168 | — |
| PRIMARY Area Under Curve (AUC) |
46913; 41328; 36811 | — |
| PRIMARY Clearance |
40.03; 13.4; 33.2 | — |
| PRIMARY Disease Control Rate (Part A) |
0; 0 | — |
| PRIMARY Response (Complete Response or Partial Response) (Part B) |
— | — |
| SECONDARY T-lymphocyte Saturation |
98.06; 99.05; 92.99 | — |
| SECONDARY Total Soluble SEMA4D |
25170.43; 19757.09; 25986.81 | — |
| SECONDARY Immunogenicity of Pepinemab |
— | — |
Summary
This phase I/II trial studies the side effects and best dose of pepinemab and to see how well it works in treating younger patients with solid tumors that have come back after treatment, or do not respond to treatment. Immunotherapy with monoclonal antibodies, such as pepinemab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Eligibility Criteria
Inclusion Criteria
- Part A: Patients with recurrent or refractory solid tumors are eligible, excluding central nervous system (CNS) tumors; patients must have had histologic verification of malignancy at original diagnosis or relapse
- Part B: Patients with recurrent or refractory osteosarcoma are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse
- 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
- Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients = = 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
- 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
- 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 = = 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; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
- 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.)
- Radiation 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, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
- Patients must not have received prior exposure to VX15/2503
- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100, 000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
- 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
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or
- A serum creatinine based on age/gender as follows:
- Age: 1 to = 16 years; Male: 1.7 mg/dL; Female: 1.4 mg/dL
- Bilirubin (sum of conjugated + unconjugated) = =
Data sourced from ClinicalTrials.gov (NCT03320330). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.