Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors

Study Overview
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Brief Summary
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At the time of study termination, NUV-422-02 was a first-in-human, open-label, Phase 1 dose escalation study designed to evaluate the safety and efficacy of NUV-422. The study population comprised adults with recurrent or refractory high-grade gliomas (HGGs), metastatic breast cancer (mBC), with and without brain metastases, and recurrent or refractory metastatic castration-resistant prostate cancer (mCRPC). All patients self-administered NUV-422 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

Official Title
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Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors

Conditions
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Glioma, Glioma, Malignant, Glioma, Mixed, Glial Cell Tumors, Breast Cancer, Breast Carcinoma, Cancer of Breast, Cancer of the Breast, Breast Tumor, Malignant Tumor of Breast, Advanced Breast Cancer, Advanced Breast Carcinoma, Metastatic Breast Cancer, Metastatic Breast Carcinoma, Prostate Cancer, Prostatic Cancer, Cancer of Prostate, Cancer of the Prostate, Prostate Neoplasm, Castrate Resistant Prostate Cancer, Castration-resistant Prostate Cancer, Castration Resistant Prostatic Neoplasms, Glioblastoma, Recurrent Glioblastoma

Intervention / Treatment
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* Drug: NUV-422


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria For All Cohorts: Recovered from toxicity to prior anti-cancer therapy Adequate bone marrow and organ function Appropriate candidate for NUV-422 monotherapy Life expectancy of > 3 months Cohort-Specific Inclusion Criteria: In addition to the inclusion criteria listed above, the following criteria apply based on enrollment into specific cohorts. High-Grade Glioma: Histologically confirmed diagnosis of high-grade glioma Evidence of recurrence after treatment (ie, surgery, radiation, or temozolomide) or refractory (or intolerant) to treatment Measurable or non-measurable disease Karnofsky Performance Status (KPS) score ≥ 60 HR+HER2- Metastatic Breast Cancer: Men and women who are not suitable for surgical resection or radiotherapy for the purpose of cure Diagnosis of locally advanced or HR+HER2- metastatic breast cancer Evidence of progression as determined by the Investigator per standard criteria Patients must have endocrine-resistant disease Prior therapy: At least 1 but not more than 4 prior lines of systemic therapies for locally advanced inoperable or metastatic BC including at least 1 prior line of hormonal therapy in combination with an approved CDK4/6 inhibitor Have no known active or symptomatic central nervous system (CNS) disease Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2 Metastatic Castration-Resistant Prostate Cancer: Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone Evidence of disease progression as determined by Investigator per standard criteria Have no known active or symptomatic CNS disease Received prior therapy with anti-androgen(s) and taxane-based chemotherapy for castration-resistant disease ECOG PS ≤ 2 Key Exclusion Criteria for All Cohorts: Have received chemotherapy, hormonal therapy (with the exception of ongoing LHRH analogs in male patients and premenopausal women), radiation, or biological anti-cancer therapy within 14 days prior to the first dose of NUV-422 Has a history of or current use of bevacizumab (glioma and brain metastases only) Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent or 21 days (or < 5 half-lives) for myelosuppressive agent prior to the first dose of NUV-422 Requires systemic corticosteroid therapy > 4 mg/day (> 2 mg/day for Expansion Cohort 2) of dexamethasone or equivalent or increasing doses of systemic corticosteroids during the 7 days prior to enrollment Requires anti-seizure medications that are known to be strong inducers of CYP3A4/5 enzymes (carbamazepine, phenytoin) or has a recent history of uncontrolled or intermittent seizures Females who are pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Dose Escalation<br>NUV-422 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached. | Drug: NUV-422<br>* NUV-422 is an investigational drug for oral dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Dose Escalation: Safety and tolerability of NUV-422 to determine the recommended Phase 2 dose (RP2D) | Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) | During the DLT period (28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, malignant glioma, metastatic breast cancer, metastatic castration-resistant prostate cancer