Phase I Study of APX005M in Pediatric CNS Tumors

  • End date
    Sep 30, 2022
  • participants needed
  • sponsor
    Pediatric Brain Tumor Consortium
Updated on 28 September 2020
Shujie Han, Ph.D., CCRA
Primary Contact
Childrens National Medical Center (5.3 mi away) Contact
+10 other location
monoclonal antibodies
growth factor
neutrophil count
tumor cells
blood transfusion
anaplastic astrocytoma
myelosuppressive chemotherapy
germ cell tumor
diffuse intrinsic pontine glioma
central nervous system tumor
craniospinal irradiation
hematopoietic stem cell transplantation
malignant central nervous system tumor
mri of spine


This phase I trial studies the side effects and best dose of APX005M in treating younger patients with primary malignant central nervous system tumor that is growing, spreading, or getting worse (progressive), or newly diagnosed diffuse intrinsic pontine glioma. APX005M can trigger activation of B cells, monocytes, and dendritic cells and stimulat cytokine release from lymphocytes and monocytes. APX005M can mediate a direct cytotoxic effect on CD40+ tumor cells.


This is a multicenter phase I trial of APX005M in patients with recurrent or refractory primary malignant central nervous system tumor, or newly diagnosed diffuse intrinsic pontine glioma.

APX005M is a humanized IgG1 mAb that binds to CD40. APX005M binds to both human and cynomolgus monkey CD40 with high affinity, triggering activation of B cells, monocytes, and dendritic cells and stimulating cytokine release from both human and monkey lymphocytes and monocytes. APX005M does not bind to mouse or rat CD40. CD40 is also expressed on many human tumor cells, and APX005M can mediate a direct cytotoxic effect on CD40+ tumor cells.

Activation of CD40 on tumor cells results in tumor cell apoptosis and inhibition of tumor growth. CD40 agonistic antibodies have demonstrated potent antitumor immune response stimulation in both animal models and cancer patients. Due to its action on both immune and tumor cells, CD40 has been studied as a target for novel cancer immunotherapy.

Apexigen has declared the adult recommended phase 2 dose to be 0.3 mg/kg because no dose limiting toxicities were encountered at that dose and the pharmacodynamic profile was similar to the 1 mg/kg maximally tolerated dose. This phase 1 clinical trial is to study APX005M in children with central nervous system tumors.

Treatment APX005M treatment for recurrent or refractory primary malignant CNS tumor patients, APX005M treatment for newly diagnosed DIPG patients
Clinical Study IdentifierNCT03389802
SponsorPediatric Brain Tumor Consortium
Last Modified on28 September 2020

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Inclusion Criteria

Is your age between 1 yrs and 21 yrs?
Gender: Male or Female
Do you have any of these conditions: Gliomas or Glioma or High-grade Astrocytoma NOS or Diffuse Intrinsic Pontine Gliomas (DIPG) or CNS Primary Tumor, Nos or Ependymoma or Medulloblastoma...?
Diagnosis -- Stratum 1: Recurrent or refractory primary malignant CNS tumor patients Patients with a histologically confirmed diagnosis of a primary malignant non-brainstem CNS tumor (excluding DIPG patients) that is recurrent, progressive, or refractory. All tumors must have histologic verification at either the time of diagnosis or recurrence except patients with marker (+) CNS germ cell tumors
Stratum 2: Newly diagnosed DIPG patients (on-hold until pediatric RP2D has
been established in Stratum 1) Patients with diffuse intrinsic pontine gliomas
(DIPGs) will be eligible 6 to 14 weeks post-completion of radiation therapy if
they do not have any evidence of progression. Patients with newly diagnosed
DIPGs, defined as tumors with a pontine epicenter and diffuse involvement of
3 or more of the pons, are eligible without histologic confirmation
Patients with pontine tumors that do not meet these criteria or not considered
to be typical intrinsic pontine gliomas will only be eligible if the tumors
have been biopsied and (1) are proven to be an anaplastic astrocytoma
glioblastoma multiforme, gliosarcoma, anaplastic mixed glioma or fibrillary
astrocytoma or (2) have a histone mutation typically seen in DIPG. Patients
with disseminated disease are not eligible, and MRI of spine must be performed
if disseminated disease is suspected by the treating physician
Available Pre-trial Tumor Tissue -- Stratum 1: Recurrent or refractory primary malignant CNS tumor patients must have adequate pre-trial frozen or FFPE tumor material (minimum of 10 unstained slides) available for use in the tumor mutation burden studies (section 9.1.5)
Stratum 2: Patients with DIPG who have pre-trial tumor tissue available are
requested to submit tissue; however, this is not required for eligibility
Age -- Patient must be 1 and 21 years of age at the time of enrollment
Prior Therapy -- Newly Diagnosed DIPG patients Patients must have not received any prior therapy for treatment of their current CNS malignancy other than radiation therapy
Refractory/Recurrent patients Patients must have recovered from the acute
treatment related toxicities (defined as < grade 1) of all prior chemotherapy
immunotherapy, radiotherapy or any other treatment modality prior to entering
this study
Myelosuppressive chemotherapy -- Patients must have received their last dose
of known myelosuppressive anticancer therapy at least 21 days prior to
enrollment or at least 42 days if nitrosourea
Biological agent: Patient must have recovered from any acute toxicity
potentially related to the agent and received their last dose of the biologic
agent 7 days prior to study enrollment
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
Monoclonal antibody treatment and agents with known prolonged half-lives: At
least three half-lives must have elapsed prior to enrollment
Radiation --
Patients must have had their last fraction of
Craniospinal irradiation (>24Gy) or total body irradiation or radiation to
greater than 50% of pelvis > 3 months prior to enrollment
Focal irradiation >6 weeks prior to enrollment Local palliative irradiation
(small port) 4 weeks
Autologous Stem Cell Transplant -- Patient must be 6 months since autologous
bone marrow/stem cell transplant prior to enrollment and have CD4 counts above
Surgery -- Patients must be at least 4 weeks (28 days) from major surgery and
fully recovered from all acute effects of prior surgical intervention
Inclusion of Women and Minorities -- Both males and females of all races and ethnic groups are eligible for this study
Neurologic Status -- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment
Patients with seizure disorders may be enrolled if seizures are well
Performance Status -- Karnofsky Performance Scale (KPS for > 16 years of age)
or Lansky Performance Score (LPS for 16 years of age) assessed within two
weeks of enrollment must be 60. Patients who are unable to walk because of
neurologic deficits, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
Organ Function --
Patients must have adequate organ and bone marrow function as defined below
Absolute Neutrophil Count (ANC) 1.0 x 109 cells/ L Platelets 100 x 109 cells/L
(unsupported, defined as no platelet transfusion within 7 days) Hemoglobin 8
g/dL (may receive transfusions) Total bilirubin 1.5 times institutional upper
limit of normal (ULN) AST(SGOT)/ALT(SGPT) 3 x institutional upper limit of
normal (ULN) Albumin 3 g/dl Serum creatinine based on age/gender as noted
below. Patients that do not meet the criteria below but have a 24 hour
Creatinine Clearance or GFR (radioisotope or iothalamate) 70 mL/min/1.73 m2
are eligible
Age Maximum Serum Creatinine (mg/dL) 1 to < 2 years 0.6, 0.6 (M, F); 2 to < 6
years 0.8, 0.8 (M, F); 6 to < 10 years 1, 1 (M, F); 10 to < 13 years 1.2, 1.2
(M, F); 13 to < 16 years 1.5, 1.4 (M, F); 16 years 1.7, 1.4 (M, F)
Cardiac Function: Left Ventricular Ejection Fraction (LVEF) > 50% ECG QTc 450
Pulmonary Function: Oxygen saturation as measured by pulse oximetry is > 93%
on room air and no evidence of dyspnea at rest
Growth Factors -- Patients must be off all colony- forming growth factor(s)
for at least 1 week prior to enrollment (i.e., filgrastim, sargramostim or
erythropoietin). 2 weeks must have elapsed if patients received PEG
Pregnancy Status -- Female patients of childbearing potential must have a negative serum or urine pregnancy test
Pregnancy Prevention -- Female subjects with childbearing potential and male subjects should use effective contraception methods (or abstain from sexual activity) while being treated with APX005M and for 30 days following treatment
Informed Consent -- The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines

Exclusion Criteria

Concurrent Illness -- Patients with any clinically significant unrelated
systemic illness (serious infections Grade 2 or significant cardiac
pulmonary, hepatic or other organ dysfunction), that in the opinion of the
investigator would compromise the patient's ability to tolerate protocol
therapy, put them at additional risk for toxicity or would interfere with the
study procedures or results
Patients with a history of any other malignancy, except patients with a
secondary brain tumor if the patient's first malignancy has been in remission
for at least 5 years from the end of treatment
Concurrent Therapy -- Patients who are receiving any other anticancer or
investigational drug therapy
Patients requiring systemic treatment with either corticosteroids (greater
than physiologic replacement, defined as dexamethasone 0.75 mg/m2/day) or
other immunosuppressive medications within 14 days of study drug
administration will be excluded. However, patients who require intermittent
use of bronchodilators or local steroid injections will not be excluded from
the study. Please see section 5.3 for a list of acceptable and unacceptable
concomitant medications as well as reporting requirements
Presence of Bulky Tumor --
Patients with bulky tumor on imaging are ineligible. Bulky tumor is defined
Tumor with any evidence of uncal herniation or midline shift Tumor that in the
opinion of the site investigator, shows significant mass effect
Allergy -- Patients with a history of severe (Grade 3) hypersensitivity reaction to a monoclonal antibody are ineligible
Allogeneic Hematopoietic Stem Cell Transplantation -- Patients who have received allogeneic hematopoietic stem cell transplantation are ineligible
Autoimmune Diseases -- Patients with active autoimmune disease or documented history of autoimmune disease/syndrome that requires ongoing systemic steroids or systemic immunosuppressive agents, except Patients with vitiligo or well controlled asthma/atopy Patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome
Inability to Participate -- Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions
Bleeding Disorder -- Patients with a known coagulopathy or bleeding diathesis or require the use of systemic anticoagulant medication are not eligible
Pregnancy Status -- Female patients must not be pregnant or breast-feeding
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