Advanced Breast Cancer, Advanced Breast Carcinoma, Breast Cancer, Breast Carcinoma, Breast Tumor, Cancer of Breast, Cancer of Prostate, Cancer of the Breast, Cancer of the Prostate, Castrate Resistant Prostate Cancer, Castration-resistant Prostate Cancer, Castration Resistant Prostatic Neoplasms, Glial Cell Tumors, Glioblastoma, Glioma, Glioma, Malignant, Glioma, Mixed, Malignant Tumor of Breast, Metastatic Breast Cancer, Metastatic Breast Carcinoma, Prostate Cancer, Prostate Neoplasm, Prostatic Cancer, Recurrent Glioblastoma
Conditions
Keywords
Phase 1, malignant glioma, metastatic breast cancer, metastatic castration-resistant prostate cancer
Brief summary
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.
Interventions
DRUGNUV-422
NUV-422 is an investigational drug for oral dosing.
Sponsors
Nuvation Bio Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Dose Escalation: Safety and tolerability of NUV-422 to determine the recommended Phase 2 dose (RP2D) | During the DLT period (28 days) | Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) |
Countries
United States
Outcome results
None listed