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

NCT03320330 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: ADVL1614NCI-2017-01103UM1CA097452
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 24

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.

Conditions

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

Outcome Measures

Primary Outcomes (9)

• 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+

• Area Under Curve (AUC)

  Mean and standard deviation for the area under the drug concentration over time curve 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+

• Clearance

  Mean and standard deviation for the rate of elimination of the drug 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+

• 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

  Up to 4 months

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

  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

  Up to 168 days

Secondary Outcomes (3)

• T-lymphocyte Saturation

  Up to 28 days

• Total Soluble SEMA4D

  Up to 28 days

• Immunogenicity of Pepinemab

  Up to 3 years

Study Arms (1)

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

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pepinemab)

Pepinemab BIOLOGICAL

Given IV

Also known as: moAb VX15/2503, VX15/2503

Treatment (pepinemab)

Pharmacological Study OTHER

Correlative studies

Treatment (pepinemab)

Eligibility Criteria

• Age: 12 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 \[TBI\]):

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (24)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

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

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (2)

• 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.

  PMID: 38520670 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.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Osteosarcoma

Interventions

pepinemab

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Emily G Greengard

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: October 25, 2017
• Study Start: January 31, 2018
• Primary Completion: December 31, 2020
• Study Completion: June 30, 2024
• Last Updated: July 15, 2024
• Results First Posted: April 26, 2022

Record last verified: 2024-07

Locations

US (24)