A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma

Summary

This is an open-label, multicenter dose-escalation study to be followed by a dose expansion to define the optimal dose of GLIX1 as monotherapy by reviewing safety and tolerability, disease characteristics and pharmacokinetic profiles and preliminary clinical activity in participants with a high grade diffuse glioma that progressed during or recurred after prior standard of care therapies or investigational therapies as clinically indicated. Patients will be treated daily with GLIX1 capsules until disease progression or unacceptable safety.

Eligibility

Main Inclusion Criteria:

* Adult patients aged ≥18 years at the time of informed consent
* Participants must have histologically confirmed Grade 3 or Grade 4 glioma
* Recurrent or progressive disease
* A maximum of two prior treatment lines
* Interval of at least 3 months since the last day off of radiotherapy, unless tumor progression and index lesion is outside the prior radiation field.
* Interval since last dose of systemic therapy and Baseline MRI of ≥28 days, except:

  * for nitrosoureas (e.g., lomustine, carmustine, fotemustine): 42 days (6 weeks)
  * for monoclonal antibodies: 42 days (6 weeks)
  * for small molecules, 4 weeks or at least 5 half-lives (whatever is longer)
* Recovered from all toxicities from prior treatments to Grade 1 or less by NCI CTCAE v6.0:
* Participants receiving corticosteroids must be on a stable or decreasing dose of ≤6 mg daily dexamethasone (or ≤40 mg prednisone) for the 7 days prior to the start of study treatment.
* Participants with seizures must be adequately controlled on a stable regimen of anti-epileptic drugs.
* Adequate performance status: Eastern Cooperative Oncology Group (ECOG) 0 or 1.
* Ability to swallow tablets or capsules.
* Adequate hematological, liver and renal function.
* Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to first dosing. Women must use a highly effective form of contraception (with Pearl Index \<1%) for the duration of the study and for at least 3 months after the last dose of study medication.
* Men with partners of childbearing potential must be willing to use condoms in combination with a second effective method of contraception by the partner during the study and for at least 3 months after the last dose of study medication.

Main Exclusion Criteria:

* Known contraindication for gadolinium (Gd) based, contrast-enhanced MRI
* Prior history of another invasive malignancy unless a complete remission was achieved at least 3 years prior to enrolment AND no additional therapy is required during the study period, except for anti-estrogen or androgen therapy and/or bisphosphonates or denosumab.
* Participants with known active or uncontrolled infection, and/or unexplained fever \>38°C in the 3 days prior to the start of study treatment.
* Major non-tumor related surgical procedure or significant traumatic injury within 28 days prior to signing of consent.
* Receiving any investigational products (defined as treatment for which there is currently no regulatory authority-approved indication) within 4 weeks or 5 half-lives (whichever is the longest) prior to Baseline MRI.

Conditions4

Interventions1

Locations3 sites

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