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

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

NUV-422-02 is a first-in-human, open-label, Phase 1/2 dose escalation and multiple expansion cohort study designed to evaluate the safety and efficacy of NUV-422. The study population is comprised of 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 will self-administer NUV-422 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nuvation Bio Inc.; Nuvation Bio, Inc.

Criteria

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