Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Trastuzumab

Antineoplastic Agents, Immunological

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with IL-15 Expanded HER2 specific CD4+ Th1 cell 0.5.0-2.5 x 10\^8, IL-7 and Expanded HER2 specific CD4+ Th1 cell 0.5.0-2.5 x 10\^8.

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with IL-15 Expanded HER2 specific CD4+ Th1 cell .25-1.2 x 10\^9, IL-7 and Expanded HER2 specific CD4+ Th1 cell .25-1.2 x 10\^9.

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with IL-15 Expanded HER2 specific CD4+ Th1 cell .5-2.5 x 10\^9, IL-7 and Expanded HER2 specific CD4+ Th1 cell .5-2.5 x 10\^9.

Participants will begin treatment with pepinemab and trastuzumab, and begin DC1 vaccines. After 6 weeks of DC1 vaccines, blood will be collected for t-cell therapy, and patients will then be treated with CD4 treated t-cells at the maximum tolerated dose determined.

Participants will receive a DC1 vaccine injection at 1.0-2.0 x 10\^7 cells, either to groin lymph notes or to tumor if accessible once a week for 3 weeks on days 1, 8 and 15. Participants will receive DC1 vaccine boosters every 3 weeks x 3.

Dendritic Cell (DC1) Vaccine

Participants will receive trastuzumab 8 mg/kg by IV week 1, then 6 mg/kg by IV beginning week 4 and continuing every 3 weeks until disease progression or intolerable toxicity.

Participants will receive pepinemab 20 mg/kg by IV beginning week 1 and continuing every 3 weeks until disease progression or intolerable toxicity.

Pepinemab

Participants will receive IL-15 expanded CD4 T cells infusion by IV Day 1 at week 8, 2 weeks from last DC1 vaccine, and IL-7 expanded CD4 T cells infusion IV at week 8 day 8.

T-Cell therapy

Kim Sprenger

Heather Han, MD

The purpose of this study is to test the safety of Adoptive T-Cell therapy following the Dendritic Cell (DC1) study vaccine given in combination with pepinemab added to standard of care therapy, trastuzumab to help people with HER2 positive breast cancer.

Patients with HER2-positive (HER2+) metastatic breast cancer will be treated with 6 weekly injections of dendritic cell (DC1) vaccines in combination with trastuzumab and pepinemab.

Investigators hypothesize these therapies will elicit CD4+ HER2 specific T cell responses. HER2 specific T cells will be expanded ex vivo which will be infused to patients subsequently following lymphodepletion therapy with cyclophosphamide. Trastuzumab and pepinemab will be given as maintenance in addition to booster DC1 vaccines.

Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine & Pepinemab /Trastuzumab in Patients w/ Metastatic HER2+ Breast Cancer

Phase 1 Study of Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine and Pepinemab / Trastuzumab in Patients With Metastatic HER2-Positive Breast Cancer

MTD of expanded CD4 T cells after treatment with DC1 vaccines and trastuzumab/pepinemab.

ORR according to RECIST criteria v1.1 and iRECIST of treatment DC1 vaccines and pepinemab/trastuzumab

To assess the 6-month clinical benefit rate (CBR) according to RECIST criteria v. 1.1 of treatment with DC1 vaccines and pepinemab/trastuzumab

To assess the 6-month CBR according to RECIST criteria v. 1.1 of treatment with expanded CD4+ T cells following DC1 vaccines and pepinemab/trastuzumab.

PFS is defined as the length of time from start of treatment to progression or death.

Vaccinex Inc.

H. Lee Moffitt Cancer Center and Research Institute

Symptoms and General Pathology

Rare Diseases

Recurrence

Osteosarcoma

Disease Attributes

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

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.

Laboratory Biomarker Analysis

Pharmacological Study

Emily G Greengard

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.

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of pepinemab (VX15/2503) administered as an intravenous infusion every 14 days to children with recurrent or refractory solid tumors. (Part A) II. To define and describe the toxicities of VX15/2503 administered on this schedule. (Parts A-B) III. To characterize the pharmacokinetics of VX15/2503 in children with recurrent or refractory cancer. (Parts A-B) IV. To preliminarily define the antitumor activity of VX15/2503 for the treatment of relapsed or refractory osteosarcoma. (Part B) V. To determine if VX15/2503 either improves the disease control rate at 4 months in patients with recurrent measurable osteosarcoma or produces an objective response rate in patients with relapsed or refractory osteosarcoma. (Part B)

SECONDARY OBJECTIVES:

I. To assess the pharmacodynamics of VX15/2503 through VX15/2503 saturation of T-lymphocytes.

II. To assess the immunogenicity of VX15/2503 in pediatric patients with recurrent or refractory cancer.

EXPLORATORY OBJECTIVES:

I. To evaluate potential biomarkers of VX15/2503 sensitivity including SEMA4D, PlexinB1, and other markers of immune cell infiltration in archival tumor tissues.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive pepinemab intravenously (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.

After completion of study treatment, patients are followed up periodically.

Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors

A Phase 1/2 Study of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors

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

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.

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.

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

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

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

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

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

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).

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

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

National Cancer Institute (NCI)

Children's Oncology Group

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.

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

Part A: 20 mg/kg (Phase 1)

Part A PK: 20 mg/kg (Expansion)

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

Part B: 20 mg/kg (Phase 2)

Patients must be ≥ 12 months and ≤ 21 years of age, recurrent or refractory solid tumors are eligible, excluding CNS tumors.

Part A

Part A PK

Part B

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Results Reporting Coordinator

The patients who had DLT in dose escalation course.

Number of Participants With Dose Limiting Toxicities

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

Half-life

Time to Maximum Concentration (T Max)

Maximum Concentration (C Max)

Area Under Curve (AUC)

Clearance

Disease Control Rate (Part A)

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

T-lymphocyte Saturation

Total Soluble SEMA4D

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine & Pepinemab /Trastuzumab in Patients w/ Metastatic HER2+ Breast Cancer	NCT05378464	HER2-positive B...	Dendritic Cell ... Trastuzumab Pepinemab T-Cell therapy	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Pepinemab in Treating Younger Patients With Recurrent, Relapsed, or Refractory Solid Tumors	NCT03320330	Recurrent Malig... Recurrent Osteo... Refractory Mali... Refractory Oste...	Laboratory Biom... Pepinemab Pharmacological...	12 Months - 30 Years	Children's Oncology Group

Spots Global Cancer Trial Database for pepinemab

Every month we try and update this database with for pepinemab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pepinemab

Every month we try and update this database with for pepinemab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pepinemab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.