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

NCT ID: NCT03320330

Last Updated: 2024-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-31
• Study Completion Date: 2024-06-30

Brief 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.

Detailed Description

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.

Conditions

Recurrent Malignant Solid Neoplasm; Recurrent Osteosarcoma; Refractory Malignant Solid Neoplasm; Refractory Osteosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (pepinemab)

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pepinemab

Intervention Type: BIOLOGICAL

Given IV

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pepinemab

Given IV

Intervention Type: BIOLOGICAL

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

moAb VX15/2503; VX15/2503

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

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily G Greengard

Role: PRINCIPAL_INVESTIGATOR

COG Phase I Consortium

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38520670 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31401903 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2017-01103

Identifier Type: REGISTRY

Identifier Source: secondary_id

ADVL1614

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL1614

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA097452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ADVL1614

Identifier Type: -

Identifier Source: org_study_id