Advanced Breast Cancer, Breast Cancer, Breast Carcinoma, Breast Tumor, Cancer of Breast, Cancer of the Breast, Malignant Tumor of Breast, Metastatic Breast Cancer
Conditions
Keywords
Phase 1, Phase 2, metastatic breast cancer, advanced breast cancer, hormone receptor positive, HR+, human epidermal growth factor receptor 2 negative, HER2-, HR+ HER2-, estrogen receptor positive, ER+, NUV-422, fulvestrant, CDK, CDK inhibition, CDK2/4/6
Brief summary
NUV-422-03 is a randomized, non-comparative Phase 1/2 dose escalation and expansion study designed to evaluate the safety and efficacy of NUV-422 in combination with fulvestrant relative to NUV-422 monotherapy and fulvestrant monotherapy. The study population is comprised of adults with HR+HER2- aBC. Patients will self-administer NUV-422 orally in 28-day cycles and receive 500 mg fulvestrant intramuscularly (IM) on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter. Patients will be treated until disease progression, toxicity, withdrawal of consent, or termination of the study.
Interventions
DRUGNUV-422
NUV-422 is an investigational drug for oral dosing.
DRUGFulvestrant
Fulvestrant
Sponsors
Nuvation Bio Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential assignment or parallel assignment will be applied (in both Phase 1 and Phase 2), depending on the stage of the study at the time of a patient's enrollment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women with diagnosis of locally advanced inoperable or metastatic HR+HER2- breast cancer 2. Evidence of disease progression on immediate prior therapy as determined by the Investigator per standard criteria 3. Patients must have received standard of care treatments for their breast cancer and be eligible to receive fulvestrant * Prior standard of care treatments must include treatment with hormonal therapy in combination with an approved CDK4/6 inhibitor 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) ≤ 1 7. Life expectancy of \> 6 months 8. Eligible to receive fulvestrant 9. Adequate bone marrow and organ function
Exclusion criteria
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 and fulvestrant 2. Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent or 21 days (of \< 5 half-lives) for myelosuppressive agent prior to first dose of NUV-422 and fulvestrant 3. Moderate liver impairment which would require a reduced dose of fulvestrant 4. Requires medications that are known to be strong inducers and/or inhibitors of CYP3A4/5 enzymes * For Phase 1b only: requires medications that are known to be moderate inducers and/or inhibitors of CYP3A4/5 enzymes 5. Known allergy or hypersensitivity to fulvestrant 6. For Phase 2 only: prior therapy with fulvestrant and/or investigational ER targeted agent 7. Females who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b Dose Escalation: Safety and tolerability of NUV-422 in combination with fulvestrant to determine the recommended Phase 2 combination dose (RP2cD) | During the DLT period (28 days) | Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and laboratory abnormalities |
| Phase 2 Dose Expansion: Objective Response Rate (ORR) | Every 8 weeks through study treatment, an average of 6 months | ORR per standard criteria |
Countries
United States
Outcome results
None listed