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

Nuvation Bio

Status and phase: Withdrawn; Phase 2; Phase 1

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

Treatments: Drug: Fulvestrant; Drug: NUV-422

Study type: Interventional

Funder types: Industry

Identifiers

NCT05191004

NUV-422-03

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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0 participants in 4 patient groups

Phase 1b Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: Fulvestrant

Drug: NUV-422

Phase 2 NUV-422 + fulvestrant

Experimental group

Description:

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.

Treatment:

Drug: Fulvestrant

Drug: NUV-422

Phase 2 NUV-422 monotherapy

Experimental group

Description:

NUV-422 will be administered orally at the RP2cD.

Treatment:

Drug: NUV-422

Phase 2 fulvestrant monotherapy

Experimental group

Description:

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

Treatment:

Drug: Fulvestrant