Pepinemab in Treating Younger Patients With Recurrent, Re... | NCT03320330

ID	Type	Description	Link
NCI-2017-01103	Registry Identifier	CTRP (Clinical Trial Reporting Program)
ADVL1614	Other Identifier	Pediatric Early Phase Clinical Trial Network
ADVL1614	Other Identifier	CTEP
UM1CA097452	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH

Label	Type	Description	Intervention Names
Treatment (pepinemab)	Experimental	Patients receive pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Biological: Pepinemab Other: Pharmacological Study

Name	Type	Description	Arm Group Labels	Other Names
Laboratory Biomarker Analysis	Other	Correlative studies	Treatment (pepinemab)

Measure	Description	Time Frame
Number of Participants With Dose Limiting Toxicities	Frequency (%) of patients with dose limiting toxicities by dose level and study part.	Up to 28 days
Patients Who Had Grade 3 or Above Toxicities With the Three Attributions, 'DEFINITE', 'POSSIBLE','PROBABLE'	Frequency of patients experiencing at least grade 3 toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by dose level and study part.	Up to 28 days
Half-life	Mean and standard deviation for the time required for the serum concentration to fall to 50% of its starting dose by dose level and study part.	Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+
Time to Maximum Concentration (T Max)	Mean and standard deviation for the time at which the maximum (peak) serum concentration occurs by dose level and study part.	Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+
Maximum Concentration (C Max)	Mean and standard deviation for the maximum (peak) serum concentration by dose level and study part.	Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+

Measure	Description	Time Frame
T-lymphocyte Saturation	Mean and standard deviation for blood samples that will be evaluated for T-lymphocyte saturation by VX15/2503 utilizing a validated flow-cytometry based assay on cycle 1 day 28 (prior to cycle 2 day 1).	Up to 28 days
Total Soluble SEMA4D

Eligibility Module

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 =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must have fully recovered 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
  - >= 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 =< 1
- Corticosteroids: 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; 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 < 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
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 135 U/L; for the purpose of this study, the ULN for ALT is 45 U/L
Serum albumin >= 2 g/dL
No clinical indications such as evidence of dyspnea at rest, or exercise intolerance due to pulmonary insufficiency
If clinical indications, pulse oximetry > 94% on room air
All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
Tissue blocks or slides must be sent; if tissue blocks or slides are unavailable, the study chair must be notified prior to enrollment

Exclusion Criteria:

Pregnant or breast-feeding women will not be entered on this study; 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
Patients receiving systemic corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of systemic corticosteroid; Note: patients who are using topical or inhaled corticosteroids are eligible
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
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
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

Name	Affiliation	Role
Emily G Greengard	COG Phase I Consortium	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital of Alabama		Birmingham	Alabama	35233	United States
Children's Hospital Los Angeles

PubMed Identifier	Type	Citation	Retractions
38520670	Derived	Greengard E, Williams R, Moriarity B, Liu X, Minard CG, Reid JM, Fisher T, Evans E, Pastore DR, Zauderer M, Voss S, Fox E, Weigel BJ. A phase 1/2 study of pepinemab in children, adolescents, or young adults with recurrent or refractory solid tumors: A children's oncology group consortium report (ADVL1614). Pediatr Blood Cancer. 2024 Jun;71(6):e30938. doi: 10.1002/pbc.30938. Epub 2024 Mar 23.
31401903	Derived	Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

ID	Title	Description
FG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 31, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Dose Limiting Toxicities

Frequency (%) of patients with dose limiting toxicities by dose level and study part.

The patients who had DLT in dose escalation course.

Posted

Count of Participants

Participants

Up to 28 days

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG002	Part B: 20 mg/kg (Phase 2)	Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Units	Counts
Participants	OG0006 OG0016 OG00214

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0021

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000						Recommended Phase 2 dose	20			2-Sided						Recommended Phase 2 dose of pepinemab (VX15/2503) is 20 mg/kg.		Other	Recommended Phase 2 dose of pepinemab (VX15/2503), administered to children with recurrent or refractory solid tumors (Part A), was determined by the rolling-6 design.

Primary

Patients Who Had Grade 3 or Above Toxicities With the Three Attributions, 'DEFINITE', 'POSSIBLE','PROBABLE'

Frequency of patients experiencing at least grade 3 toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by dose level and study part.

Part A and B Patients

Posted

Count of Participants

Participants

Up to 28 days

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG002	Part B: 20 mg/kg (Phase 2)

Primary

Half-life

Mean and standard deviation for the time required for the serum concentration to fall to 50% of its starting dose by dose level and study part.

all toxicity evaluable patients

Posted

Mean

Standard Deviation

hours

Prior to, at the end of, and 2 hours after infusion on day 1 of cycles 1-2; days 4 & 8 of cycle 1; prior to and the end of infusion on day 15 of cycle 1; prior to start of infusion on day 15 of cycle 2; prior to start of infusion on day 1 of cycles 3+

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Primary

Time to Maximum Concentration (T Max)

Mean and standard deviation for the time at which the maximum (peak) serum concentration occurs by dose level and study part.

All toxicity evaluable patients

Posted

Mean

Standard Deviation

hours

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Primary

Maximum Concentration (C Max)

Mean and standard deviation for the maximum (peak) serum concentration by dose level and study part.

All toxicity evaluable patients

Posted

Mean

Standard Deviation

ug/ml

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG002

Primary

Area Under Curve (AUC)

Mean and standard deviation for the area under the drug concentration over time curve by dose level and study part.

All toxicity evaluable patients

Posted

Mean

Standard Deviation

hr*ug/ml

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Primary

Clearance

Mean and standard deviation for the rate of elimination of the drug by dose level and study part.

All toxicity evaluable patients

Posted

Mean

Standard Deviation

ml/hr

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG002

Primary

Disease Control Rate (Part A)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no new lesions detected and <20% increase in sum of smallest diameters of lesions; Disease Control Rate = CR + PR + SD

Posted

Number

participants

Up to 4 months

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Primary

Response (Complete Response or Partial Response) (Part B)

Posted

Number

participants

Up to 168 days

ID	Title	Description
OG000	Part B: 20 mg/kg (Phase 2)	Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Units	Counts
Participants	OG000

Secondary

T-lymphocyte Saturation

Mean and standard deviation for blood samples that will be evaluated for T-lymphocyte saturation by VX15/2503 utilizing a validated flow-cytometry based assay on cycle 1 day 28 (prior to cycle 2 day 1).

All Eligible Patients

Posted

Mean

Standard Deviation

percent of T-lymphocyte Saturation

Up to 28 days

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG002	Part B: 20 mg/kg (Phase 2)

Secondary

Total Soluble SEMA4D

Mean and standard deviation of blood and serum samples evaluated for total soluble SEMA4D through a qualified enzyme-linked immunosorbent assay (ELISA) assay.

All eligible patients

Posted

Mean

Standard Deviation

pg/mL

Up to 28 days

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG002	Part B: 20 mg/kg (Phase 2)	Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Secondary

Immunogenicity of Pepinemab

Mean and standard deviation of immunogenicity assessed in serum through a qualified ELISA.

The planned assays for ADA were unable to generate interpretable results due to limitations of the assay which resulted in higher levels of false positive results. These samples were re-run and only one confirmed positive result out of 81 samples, which was considered to be a true positive ADA. Even this one confirmed positive result had a negative titer, which further signifies a possible false positive or very low-level ADA. Therefore, results were determined to be unreliable and invalid.

Posted

Up to 3 years

ID	Title	Description
OG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies
OG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Alkaline phosphatase increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0026 affected14 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Creatinine increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Depressed level of consciousness	Nervous system disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0023 affected14 at risk
Electrocardiogram QT corrected interval prolonged	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Esophagitis	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Hearing impaired	Ear and labyrinth disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Hypophosphatemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0023 affected14 at risk
Irregular menstruation	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0025 affected14 at risk
Mucosal infection	Infections and infestations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, PROGRESSIVE DISEASE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Obesity	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Pain	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Pericardial effusion	Cardiac disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Peripheral motor neuropathy	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Thromboembolic event	Vascular disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
White blood cell decreased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Activated partial thromboplastin time prolonged	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Agitation	Psychiatric disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0024 affected14 at risk
Alkaline phosphatase increased	Investigations	Systematic Assessment	EG0006 affected6 at risk EG0011 affected6 at risk EG0028 affected14 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0022 affected14 at risk
Alopecia	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0025 affected14 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0004 affected6 at risk EG0014 affected6 at risk EG00210 affected14 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0027 affected14 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0003 affected6 at risk EG0011 affected6 at risk EG0027 affected14 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0002 affected6 at risk EG0014 affected6 at risk EG0024 affected14 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0028 affected14 at risk
Blood and lymphatic system disorders - Other, Neutrophil count increased	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Blood and lymphatic system disorders - Other, RBC decreased	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Blood and lymphatic system disorders - Other, White Blood Cell Count Increased	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Blood bilirubin increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Blurred vision	Eye disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Body odor	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Bone pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Breast pain	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Bruising	Injury, poisoning and procedural complications	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Bullous dermatitis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Burn	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Buttock pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Chills	General disorders	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0024 affected14 at risk
Cholesterol high	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Concentration impairment	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Confusion	Psychiatric disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0025 affected14 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 affected6 at risk EG0011 affected6 at risk EG0029 affected14 at risk
Creatinine increased	Investigations	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Cushingoid	Endocrine disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0003 affected6 at risk EG0012 affected6 at risk EG0022 affected14 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Dry mouth	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Dry skin	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected6 at risk EG0011 affected6 at risk EG0024 affected14 at risk
Ear and labyrinth disorders - Other,	Ear and labyrinth disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Edema limbs	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0023 affected14 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Erectile dysfunction	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Eye disorders - Other, Anisocoria	Eye disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Eye disorders - Other, Vision decreased	Eye disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Fatigue	General disorders	Systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG0026 affected14 at risk
Fecal incontinence	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Fever	General disorders	Systematic Assessment	EG0003 affected6 at risk EG0012 affected6 at risk EG00210 affected14 at risk
Flank pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Flushing	Vascular disorders	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0020 affected14 at risk
Gait disturbance	General disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
General disorders and administration site conditions - Other, Generalized edema	General disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
General disorders and administration site conditions - Other, SWEATING	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Genital edema	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Gynecomastia	Reproductive system and breast disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Hallucinations	Psychiatric disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0027 affected14 at risk
Hearing impaired	Ear and labyrinth disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Hematuria	Renal and urinary disorders	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0022 affected14 at risk
Hemoglobin increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Hemoglobinuria	Renal and urinary disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Hoarseness	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Hot flashes	Vascular disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0003 affected6 at risk EG0014 affected6 at risk EG0029 affected14 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Hyperkalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Hypermagnesemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0022 affected14 at risk
Hypernatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG0004 affected6 at risk EG0012 affected6 at risk EG0021 affected14 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	Systematic Assessment	EG0003 affected6 at risk EG0011 affected6 at risk EG0028 affected14 at risk
Hypocalcemia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0025 affected14 at risk
Hypoglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0028 affected14 at risk
Hypomagnesemia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0022 affected14 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0026 affected14 at risk
Hypophosphatemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0027 affected14 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0023 affected14 at risk
Hypothyroidism	Endocrine disorders	Systematic Assessment	EG0000 affected6 at risk EG0012 affected6 at risk EG0020 affected14 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
INR increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Infusion related reaction	General disorders	Systematic Assessment	EG0003 affected6 at risk EG0012 affected6 at risk EG0023 affected14 at risk
Infusion related reaction	Injury, poisoning and procedural complications	Systematic Assessment	EG0003 affected6 at risk EG0012 affected6 at risk EG0022 affected14 at risk
Infusion site extravasation	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Injury, poisoning and procedural complications - Other, OPEN WOUND	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0025 affected14 at risk
Investigations - Other, BICARBONATE LOW	Investigations	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Investigations - Other, ELEVATED BICARBONATE SERUM LOW	Investigations	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Investigations - Other, ELEVATED LDH	Investigations	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Investigations - Other, HYOCHLOREMIA	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Investigations - Other, HYPOCHLOREMIA	Investigations	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Investigations - Other, LDH INCREASED	Investigations	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Investigations - Other, LDH increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Investigations - Other, Monocytes Decrease	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Investigations - Other, Monocytes Increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Investigations - Other, bicarbonate serum low	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Investigations - Other, elevated BUN	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Investigations - Other, elevated LDH	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Irritability	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0024 affected14 at risk
Keratitis	Eye disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Kyphosis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Lethargy	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Lipase increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Localized edema	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Lung infection	Infections and infestations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0013 affected6 at risk EG0029 affected14 at risk
Malaise	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Memory impairment	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Metabolism and nutrition disorders - Other, HYPOCHLOREMIA	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Metabolism and nutrition disorders - Other, Hyperchloremia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Metabolism and nutrition disorders - Other, Increased bicarbonates	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Metabolism and nutrition disorders - Other, Increased phosphorus level	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Mucositis oral	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0024 affected14 at risk
Muscle weakness trunk	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Musculoskeletal and connective tissue disorder - Other, DIFFICULTY FULLY EXTENDING LEFT LEG	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Musculoskeletal and connective tissue disorder - Other, LEFT MEDIAL THIGH SWELLING	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Musculoskeletal and connective tissue disorder - Other, LIMP	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Musculoskeletal and connective tissue disorder - Other, MUSCLE ACHES/PAIN	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Musculoskeletal and connective tissue disorder - Other, muscle spasm	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Nail discoloration	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0004 affected6 at risk EG0011 affected6 at risk EG0027 affected14 at risk
Neck pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Nervous system disorders - Other, Spinal cord compression	Nervous system disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Neuralgia	Nervous system disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0023 affected14 at risk
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0025 affected14 at risk
Optic nerve disorder	Eye disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Oral pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Pain	General disorders	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0023 affected14 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0003 affected6 at risk EG0013 affected6 at risk EG0026 affected14 at risk
Paresthesia	Nervous system disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0022 affected14 at risk
Pelvic pain	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Pericardial effusion	Cardiac disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0023 affected14 at risk
Phantom pain	Nervous system disorders	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Photophobia	Eye disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0025 affected14 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected6 at risk EG0010 affected6 at risk EG0026 affected14 at risk
Pleural hemorrhage	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Proteinuria	Renal and urinary disorders	Systematic Assessment	EG0001 affected6 at risk EG0012 affected6 at risk EG0025 affected14 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Radiation recall reaction (dermatologic)	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Reproductive system and breast disorders - Other, GENITAL HYPERSENSITIVITY	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Respiratory, thoracic and mediastinal disorders - Other, HEMOPTYSIS	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Respiratory, thoracic and mediastinal disorders - Other, Hemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Respiratory, thoracic and mediastinal disorders - Other, MILD RHINORREA G1	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Respiratory, thoracic and mediastinal disorders - Other, RHINORRHEA	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Restlessness	Psychiatric disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Serum amylase increased	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Sinus bradycardia	Cardiac disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Sinus tachycardia	Cardiac disorders	Systematic Assessment	EG0005 affected6 at risk EG0012 affected6 at risk EG0027 affected14 at risk
Skin and subcutaneous tissue disorders - Other, FACIAL SORES	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Skin and subcutaneous tissue disorders - Other, FISTULA - SUPERIOR LATERAL STUMP WOUND	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Skin and subcutaneous tissue disorders - Other, MOTTLING OF FINGERS	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Skin and subcutaneous tissue disorders - Other, SEBORRHEIC DERMATITIS	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected6 at risk EG0010 affected6 at risk EG0020 affected14 at risk
Skin and subcutaneous tissue disorders - Other, Skin breakdown	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Somnolence	Nervous system disorders	Systematic Assessment	EG0002 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Stomach pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Testicular pain	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
Thromboembolic event	Vascular disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Upper respiratory infection	Infections and infestations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Urinary retention	Renal and urinary disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0023 affected14 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Urinary urgency	Renal and urinary disorders	Systematic Assessment	EG0000 affected6 at risk EG0010 affected6 at risk EG0021 affected14 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0003 affected6 at risk EG0011 affected6 at risk EG0024 affected14 at risk
Weight gain	Investigations	Systematic Assessment	EG0000 affected6 at risk EG0011 affected6 at risk EG0021 affected14 at risk
Weight loss	Investigations	Systematic Assessment	EG0002 affected6 at risk EG0010 affected6 at risk EG0022 affected14 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected6 at risk EG0011 affected6 at risk EG0020 affected14 at risk
White blood cell decreased	Investigations	Systematic Assessment	EG0002 affected6 at risk EG0013 affected6 at risk EG0025 affected14 at risk

ID	Title	Description
BG000	Part A	Patients must be ≥ 12 months and ≤ 21 years of age, recurrent or refractory solid tumors are eligible, excluding CNS tumors.
BG001	Part A PK	Patients must be ≥ 12 months and ≤ 21 years of age, recurrent or refractory solid tumors are eligible, excluding CNS tumors.
BG002	Part B	Patients must be ≥ 12 months and ≤ 21 years of age, recurrent or refractory solid tumors are eligible, excluding CNS tumors.
BG003	Total	Total of all reporting groups

ID	Term
D018213	Neoplasms, Bone Tissue
D009372	Neoplasms, Connective Tissue
D018204	Neoplasms, Connective and Soft Tissue
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D012509	Sarcoma

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A: 20 mg/kg (Phase 1)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies	1	6	4	6	6	6
EG001	Part A PK: 20 mg/kg (Expansion)	Patients ≥ 12 months and ≤ 21 years of age with recurrent or refractory solid tumors, excluding CNS tumors, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies	0	6	4	6	6	6
EG002	Part B: 20 mg/kg (Phase 2)	Patients ≥ 12 months and ≤ 30 years with recurrent or refractory osteosarcoma, receive 20 mg/kg of pepinemab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pepinemab: Given IV Pharmacological Study: Correlative studies	3	14	10	14	14	14