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

Key Inclusion Criteria

For All Phases and 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.

Phase 1 (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

Phase 1 (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

Phase 1 (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

Phase 1 Surgical Substudy (Glioblastoma):

Histologically confirmed diagnosis of glioblastoma
Received prior therapy with radiation or radiation plus temozolomide
Radiographic evidence of progression as determined by the Investigator per standard criteria
KPS score ≥ 70
Eligible for surgical resection

Phase 2 Expansion Cohort 1 (Glioblastoma):

Histologically confirmed diagnosis of IDH-WT glioblastoma
Received prior therapy with radiation plus temozolomide
Radiographic evidence of progression and measurable disease as determined by the Investigator per standard criteria
KPS score ≥ 70

Phase 2 Expansion Cohort 2 (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 and measurable disease as determined by the Investigator per standard criteria
Have no known active or symptomatic CNS disease
ECOG PS ≤ 2

Phase 2 Expansion Cohort 3 (Metastatic Castration-Resistant Prostate Cancer):

Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone
Have radiographic or biochemical evidence of progression and measurable disease as determined by the Investigator per standard criteria; patients without measurable disease must have PSA ≥ 2 ng/mL
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

Phase 2 Expansion Cohort 4 (HR+HER2- Metastatic Breast Cancer with Brain Metastases):

Men and women who are not suitable for surgical resection or radiotherapy for the purpose of cure
Diagnosis of HR+HER2- metastatic breast cancer with brain lesion(s)
Evidence of progression and measurable disease as determined by the Investigator per standard criteria
ECOG PS ≤ 2
At least 1 measurable brain lesion per standard criteria

Key Exclusion Criteria (for All Phases and 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