Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC

Phase 1

Withdrawn

• Conditions: Advanced Breast Cancer; Breast Tumor; Metastatic Breast Cancer; Breast Carcinoma; Cancer of the Breast; Breast Cancer; Malignant Tumor of Breast; Cancer of Breast
• Interventions: Drug: NUV-422; Drug: Fulvestrant

• Registration Number: NCT05191004
• Lead Sponsor: Nuvation Bio Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-12-22
• Study First Submitted QC: 2022-01-12
• Study First Posted: 2022-01-13
• Study Start: 2022-09
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-10
• Last Update Posted: 2023-07-11
• Primary Completion: 2025-06
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1b Dose Escalation	NUV-422	NUV-422 will be administered orally at escalating dose levels in combination with fulvestrant until the recommended Phase 2 combination dose (RP2cD) is determined. 500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
Phase 2 fulvestrant monotherapy	Fulvestrant	500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
Phase 2 NUV-422 monotherapy	NUV-422	NUV-422 will be administered orally at the RP2cD.
Phase 2 NUV-422 + fulvestrant	NUV-422	NUV-422 will be administered orally at the RP2cD in combination with fulvestrant. 500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
Phase 1b Dose Escalation	Fulvestrant	NUV-422 will be administered orally at escalating dose levels in combination with fulvestrant until the recommended Phase 2 combination dose (RP2cD) is determined. 500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.
Phase 2 NUV-422 + fulvestrant	Fulvestrant	NUV-422 will be administered orally at the RP2cD in combination with fulvestrant. 500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (5)

Pennsylvania Cancer Specialists and Research Institute; 🇺🇸 Gettysburg, Pennsylvania, United States

Pacific Cancer Medical Center, Inc.; 🇺🇸 Anaheim, California, United States

Compassionate Cancer Care Research Inc.; 🇺🇸 Fountain Valley, California, United States

Gabrail Cancer Center Research; 🇺🇸 Canton, Ohio, United States

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States