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

Sponsor

Nuvation Bio Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05191004

Collaborator

(none)

236

Enrollment

Locations

Arms

Anticipated Duration (Months)

47.2

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer Metastatic Breast Cancer Breast Cancer Breast Carcinoma Cancer of the Breast Cancer of Breast Malignant Tumor of Breast Breast Tumor	Drug: NUV-422 Drug: Fulvestrant	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

236 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized, Non-Comparative Phase 1/2 Study of NUV-422 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative (HR+HER2-) Advanced Breast Cancer (aBC)

Anticipated Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1b Dose Escalation 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.	Drug: NUV-422 NUV-422 is an investigational drug for oral dosing. Drug: Fulvestrant Fulvestrant Other Names: Faslodex
Experimental: Phase 2 NUV-422 + 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.	Drug: NUV-422 NUV-422 is an investigational drug for oral dosing. Drug: Fulvestrant Fulvestrant Other Names: Faslodex
Experimental: Phase 2 NUV-422 monotherapy NUV-422 will be administered orally at the RP2cD.	Drug: NUV-422 NUV-422 is an investigational drug for oral dosing.
Experimental: Phase 2 fulvestrant monotherapy 500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.	Drug: Fulvestrant Fulvestrant Other Names: Faslodex

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women with diagnosis of locally advanced inoperable or metastatic HR+HER2- breast cancer
Evidence of disease progression on immediate prior therapy as determined by the Investigator per standard criteria
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

Patients must have endocrine-resistant disease
Have no known active or symptomatic central nervous system (CNS) disease
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1
Life expectancy of > 6 months
Eligible to receive fulvestrant
Adequate bone marrow and organ function

Exclusion Criteria:

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
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
Moderate liver impairment which would require a reduced dose of fulvestrant
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

Known allergy or hypersensitivity to fulvestrant
For Phase 2 only: prior therapy with fulvestrant and/or investigational ER targeted agent
Females who are pregnant or breast feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Cancer Medical Center, Inc.	Anaheim	California	United States	92801
2	Compassionate Cancer Care Research Inc.	Fountain Valley	California	United States	92708
3	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
4	Pennsylvania Cancer Specialists and Research Institute	Gettysburg	Pennsylvania	United States	17325
5	NEXT Virginia	Fairfax	Virginia	United States	22031