Key Inclusion Criteria

        For All Phases and 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.

        Phase 1 (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

        Phase 1 (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. Have no known active or symptomatic central nervous system (CNS) disease

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

        Phase 1 (Metastatic Castration-Resistant Prostate Cancer):

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

          2. Have radiographic or biochemical evidence of progression as determined by the
             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

        Phase 2 Expansion Cohort 1 (Glioblastoma):

          1. Histologically confirmed diagnosis of glioblastoma

          2. Received prior therapy with radiation or radiation plus temozolomide

          3. Radiographic evidence of progression and measurable disease as determined by the
             Investigator per standard criteria

          4. KPS score ≥ 70

        Phase 2 Expansion Cohort 2 (Glioblastoma):

          1. Histologically confirmed diagnosis of glioblastoma

          2. Received prior therapy with radiation or radiation plus temozolomide

          3. Radiographic evidence of progression and measurable disease as determined by the
             Investigator per standard criteria

          4. KPS score ≥ 70

          5. Eligible for surgical resection

        Phase 2 Expansion Cohort 3 (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 and measurable disease as determined by the Investigator per
             standard criteria

          4. Have no known active or symptomatic CNS disease

          5. ECOG PS ≤ 2

        Phase 2 Expansion Cohort 4 (Metastatic Castration-Resistant Prostate Cancer):

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

          2. Have radiographic or biochemical evidence of progression and measurable disease as
             determined by the 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

        Phase 2 Expansion Cohort 5 (HR+HER2- Metastatic Breast Cancer with brain metastases)

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

          2. Diagnosis of HR+HER2- metastatic breast cancer with brain lesion(s)

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

          4. ECOG PS ≤ 2

        Key Exclusion Criteria for All Phases and 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