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

NCT05191004 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: NUV-422-03
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

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.

Conditions

Advanced Breast Cancer; Metastatic Breast Cancer; Breast Cancer; Breast Carcinoma; Cancer of the Breast; Cancer of Breast; Malignant Tumor of Breast; Breast Tumor

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

Outcome Measures

Primary Outcomes (2)

• Phase 1b Dose Escalation: Safety and tolerability of NUV-422 in combination with fulvestrant to determine the recommended Phase 2 combination dose (RP2cD)

  Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and laboratory abnormalities

  During the DLT period (28 days)

• Phase 2 Dose Expansion: Objective Response Rate (ORR)

  ORR per standard criteria

  Every 8 weeks through study treatment, an average of 6 months

Study Arms (4)

Phase 1b Dose Escalation

EXPERIMENTAL

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; Drug: Fulvestrant

Phase 2 NUV-422 + fulvestrant

EXPERIMENTAL

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; Drug: Fulvestrant

Phase 2 NUV-422 monotherapy

EXPERIMENTAL

NUV-422 will be administered orally at the RP2cD.

Drug: NUV-422

Phase 2 fulvestrant monotherapy

EXPERIMENTAL

500 mg fulvestrant will be administered IM on Days 1 and 15 of Cycle 1 and Day 1 of every cycle thereafter.

Drug: Fulvestrant

Interventions

NUV-422 DRUG

NUV-422 is an investigational drug for oral dosing.

Phase 1b Dose Escalation; Phase 2 NUV-422 + fulvestrant; Phase 2 NUV-422 monotherapy

Fulvestrant DRUG

Fulvestrant

Also known as: Faslodex

Phase 1b Dose Escalation; Phase 2 NUV-422 + fulvestrant; Phase 2 fulvestrant monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nuvation Bio Inc.: lead

Study Sites (5)

Pacific Cancer Medical Center, Inc.

Anaheim, California, 92801, United States

Location

Compassionate Cancer Care Research Inc.

Fountain Valley, California, 92708, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Pennsylvania Cancer Specialists and Research Institute

Gettysburg, Pennsylvania, 17325, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: January 13, 2022
• Study Start: September 1, 2022
• Primary Completion: June 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 11, 2023

Record last verified: 2023-07

Locations

US (5)