A 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

Protocol # :
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
Recurrent Glioblastoma
Disease Sites
Brain and Nervous System
Principal Investigator
Wen, Patrick, Yung

Trial Description

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.

Eligibility Requirements

Key Inclusion Criteria

For All Cohorts:

1. Recovered from toxicity to prior anti-cancer therapy

2. Adequate bone marrow and organ function

3. Appropriate candidate for NUV-422 monotherapy

4. 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:

1. Histologically confirmed diagnosis of high-grade glioma

2. Evidence of recurrence after treatment (ie, surgery, radiation, or temozolomide) or
refractory (or intolerant) to treatment

3. Measurable or non-measurable disease

4. Karnofsky Performance Status (KPS) score ≥ 60

HR+HER2- Metastatic Breast Cancer:

1. Men and women who are not suitable for surgical resection or radiotherapy for the
purpose of cure

2. Diagnosis of locally advanced or HR+HER2- metastatic breast cancer

3. Evidence of progression as determined by the Investigator per standard criteria

4. Patients must have endocrine-resistant disease

5. 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

6. Have no known active or symptomatic central nervous system (CNS) disease

7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2

Metastatic Castration-Resistant Prostate Cancer:

1. Diagnosis of metastatic castration-resistant prostate cancer with disease progression
despite castrate levels of testosterone

2. Evidence of disease progression as determined by Investigator per standard criteria

3. Have no known active or symptomatic CNS disease

4. Received prior therapy with anti-androgen(s) and taxane-based chemotherapy for
castration-resistant disease

5. ECOG PS ≤ 2

Key Exclusion Criteria for All Cohorts:

1. 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

2. Has a history of or current use of bevacizumab (glioma and brain metastases only)

3. 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

4. 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

5. 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

6. Females who are pregnant or breast feeding