Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis
An Open-label Phase 1/2 Dose Finding, Safety and Efficacy Study of Oral NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Uncontrolled Brain Metastasis in Patients With Select Solid Tumors.
1 other identifier
interventional
134
1 country
6
Brief Summary
This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 alone for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH- mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled metastases to the brain. The study will have three phases, Phase 1, Phase 2a and Phase 2b.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2023
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 17, 2023
CompletedFirst Posted
Study publicly available on registry
September 21, 2023
CompletedStudy Start
First participant enrolled
November 1, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2027
March 2, 2026
January 1, 2026
3.3 years
August 17, 2023
February 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Phase 1: safety and tolerability of increasing dose levels of orally administered NEO212 alone in patients with Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or patients with select solid tumors with uncontrolled metastases to the brain
As determined by incidence and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0
6 months
Phase 1: Identify the maximum tolerated dose (MTD) of NEO212
Maximum Tolerated Dose of NEO212 as determined by the dose escalation rules.
6 months
Phase 1: Determine the recommended Phase 2 dose (RP2D) of NEO212
Determine the recommended Phase 2 dose (RP2D) of NEO212
6 months
Phase 2a: Assess the safety and tolerability of orally administered NEO212 in combination with select SOC regimens following a standard 3+3 design in patients with select solid tumors with uncontrolled metastases to the brain
Determined by incidence and severity of adverse events determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0).
6 months
Phase 2b: Determine the intracranial progression-free survival rate at six months (PFS6) of orally administered NEO212 alone in patients with Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype.
Determine the intracranial progression-free survival rate at six months (PFS6) of orally administered NEO212 alone in patients with Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype.
6 months
Phase 2b: Determine the intracranial progression-free survival rate at six months (PFS6) of orally administered NEO212 in combination with select SOC regimens in patients with select solid tumors with uncontrolled metastases to the brain.
Determine the intracranial progression-free survival rate at six months (PFS6) of orally administered NEO212 in combination with select SOC regimens in patients with select solid tumors (see Appendix 2) with uncontrolled metastases to the brain.
6 months
Study Arms (8)
Phase 2a Safety Run-In - NEO212 and Ipilimumab
EXPERIMENTAL\- Unresectable or metastatic melanoma with uncontrolled metastases to the brain. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Ipilimumab - 3 mg/kg administered IV over 90 minutes every 3 weeks for a maximum of 3 doses per package insert.
Phase 2a Safety Run-In - NEO212 and Pembrolizumab
EXPERIMENTALThe following primary cancers with uncontrolled metrastases to the brain: * Unresectable or metastatic melanoma. * NSCLC expressing PD-L1, with no EGFR or ALK genomic tumor aberrations. * Metastatic NSCLC whose tumors express PD-L1. * EGFR or ALK genomic tumor aberrations must have disease progression. * SCLC. * Unresectable, recurrent HNSCC whose tumors express PD-L1. * HNSCC on or after platinum-containing chemotherapy. * Urothelial carcinoma whose tumors express PD-L1. * Urothelial carcinoma. * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). * Microsatellite Instability-high or Mismatch Repair Deficient Colorectal Cancer (CRC). * Gastric or gastroesophageal junction adenocarcinoma. * Esophageal or gastroesophageal juncUon (GEJ). * Cervical cancer. * Merkel cell carcinoma. NEO212 - Same as Arm 1. Pembrolizumab - 200 mg administered every 3 weeks per package insert.
Phase 2a Safety Run-In - NEO212 and Nivolumab
EXPERIMENTALThe following primary cancers with uncontrolled metrastases to the brain: * Unresectable or metastatic melanoma. * Metastatic non-small cell lung cancer. * Advanced renal cell carcinoma. * Squamous cell carcinoma of the head and neck. * Urothelial carcinoma. * Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. * Unresectable esophageal squamous cell carcinoma (ESCC). NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Nivolumab - 240 mg administered every 2 weeks per package insert
Phase 2a Safety Run-In - NEO212 and Stivarga (Regorafenib)
EXPERIMENTAL\- Colorectal cancer (CRC) with uncontrolled metastases to the brain who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anU-EGFR therapy. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Stivarga - 160 mg orally, once daily for the first 21 days of each 28-day cycle per package insert
Phase 2a Safety Run-In - NEO212 and CarbolaUn (ParaplaUn) + Paclitaxel (Taxol)
EXPERIMENTAL\- Colorectal cancer (CRC) with uncontrolled metastases to the brain. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. Carboplatin - 300 mg/m2 IV on day 1 every 4 weeks for 6 cycles per package insert. Paclitaxel - 135mg/m2 IV administered over 24 hours, every 3 weeks per package insert.
Phase 2a Safety Run-In - NEO212 and FOLFIRI (Zaltrap) + Bevacizumab (Avastin)
EXPERIMENTAL\- Metastatic colorectal cancer (mCRC) with uncontrolled metastases to the brain, that is resistant to or has progressed following an oxaliplatin-containing regimen NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. FOLFIRI - 4 mg/kg aIV over 1 hour every 2 weeks. Bevacizumab - 10 mg/kg IV every 2 weeks.
Phase 2b efficacy - NEO212 for Astrocytoma IDH-mutant and Glioblastoma IDH-wildtype
EXPERIMENTALPatients receiving NEO212 alone for treatment of Astrocytoma IDH-mutant and Glioblastoma IDH-wildtype. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules.
Phase 2b efficacy - NEO212 & SOC for Uncontrolled Metastases to the Brain
EXPERIMENTALPatients receiving NEO212 in combination with select standard of care treatments for treatment of uncontrolled metastases to the brain. NEO212 - Starting one dose level under RP2D administered orally on days 1 - 5 of a 28-day treatment cycle, escalated to RP2D per Protocol dose escalation rules. SOC treatments established to be safe in Phase 2a of the study will be used in this arm of Phase 2b.
Interventions
NEO212 is a novel chemical entity that was generated by covalent conjugation of temozolomide (TMZ) with perillyl alcohol (POH).
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. Cytotoxic T lymphocytes can recognize and destroy cancer cells.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is given by slow injection into a vein.
Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer.
Regorafenib, sold under the brand name Stivarga among others, is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase. Regorafenib shows anti-angiogenic activity due to its dual targeted VEGFR2-TIE2 tyrosine kinase inhibition
Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used by injection into a vein.
Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered by intravenous injection
FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer. It is made up of the following drugs: FOL - folinic acid (leucovorin), a vitamin B derivative with multiple applications, which in this context increases the cytotoxicity of 5-fluorouracil; F - fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops synthesis; and IRI - irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating.
Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma
Eligibility Criteria
You may qualify if:
- Patient must be ≥ 18yrs of age.
- Patient must have the ability to understand, and the willingness to sign, a written informed consent form.
- Patient has been on a stable or decreasing dose of steroids for at least five days prior to the date of informed consent.
- Any toxicity from prior therapy must be resolved or at maximum Grade 1 prior to initiation of NEO212.
- If progression of disease occurs within 90 days or conformal radiation, the progression/recurrence must be outside of the radiation field or proven by biopsy/resection.
- Patient with Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype must have a Karnofsky Performance Status (KPS) of ≥ 60.
- Patient with select solid tumors must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Patient must have an expected survival or at least three months.
- Patient must have a baseline MRI of the brain with gadolinium within 14 days of administration of NEO212.
- Patient with select solid tumors must have a baseline CT scan with IV contrast and oral contrast of neck, chest, abdomen and pelvis within 14 days of administration of NEO212.
- Patients must be able to comply with all study assessments.
- If patient suffers from seizures (s)he must be controlled on a stable dose of anti-epileptics for 14-days prior to the date of informed consent.
- Patient must have adequate organ and marrow function as follows:
- Absolute neutrophil count ≥ 1,500/microliter
- Platelets ≥ 100,000/microliter
- +32 more criteria
You may not qualify if:
- Patient in Phase 1 concurrently receiving any other antitumor therapy.
- Patient in Phase 2a or 2b who is concurrently receiving any SOC therapy not listed in Appendix 1.
- Patients with metastases to the spinal cord parenchyma.
- Patients with metastases to the meninges.
- Patient has received stereotactic or highly conformal radiotherapy to CNS lesions within 2 weeks before receipt of NEO212.
- Patient with history of known leptomeningeal involvement.
- Patient has prior history or new diagnosis of secondary cancer within five years prior to the date of informed consent, except for basal cell carcinoma or squamous cell carcinoma of the skin.
- Patient has a corrected QT interval (using Fridericia's correction formula) (QTcF) of \>470 msec, a history of additional risk factors for TdP (e.g. heart failure, hypokalemia), and/or the use of concomitant medications that prolong QT/QTc interval.
- Patient had surgery within 7 days prior to the date of informed consent.
- Patient has not recovered to Grade 1 from treatment related adverse events due to chemotherapy, immunotherapy, or radiation therapy.
- Patient had prior treatment with perillyl alcohol.
- Patient has a history of allergic reactions attributed to perillyl alcohol.
- Patients in Phase 2b with Astrocytoma IDH-mutant, or Glioblastoma IDH-wildtype who have had more than one recurrence or progression of his/her primary CNS tumor(s).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Precision NextGen Oncology
Beverly Hills, California, 90212, United States
OPN Healthcare, Inc
Glendale, California, 91203, United States
University of Southern California
Los Angeles, California, 90033, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Baylor, Scott and White Research Institute
Dallas, Texas, 75246, United States
Northwest Medical Specialties
Tacoma, Washington, 98405, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Tom Chen, MD, PhD
NeOnc Technologies
- STUDY DIRECTOR
Josh Neman, PhD
NeOnc Technologies Holdings, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 17, 2023
First Posted
September 21, 2023
Study Start
November 1, 2023
Primary Completion (Estimated)
February 28, 2027
Study Completion (Estimated)
August 31, 2027
Last Updated
March 2, 2026
Record last verified: 2026-01