Study of NUV-422 in Combination With Enzalutamide in Patients With mCRPC

Phase 1

Withdrawn

• Conditions: Cancer of Prostate; Prostate Cancer; Castration Resistant Prostatic Neoplasms; Prostatic Cancer; Cancer of the Prostate; Prostate Neoplasm; Castrate Resistant Prostate Cancer; Castration Resistant Prostatic Cancer
• Interventions: Drug: NUV-422; Drug: Enzalutamide

• Registration Number: NCT05191017
• Lead Sponsor: Nuvation Bio Inc.

Brief Summary

NUV-422-04 is an open-label Phase 1b/2 dose escalation and expansion study designed to evaluate the safety and efficacy of NUV-422 in combination with enzalutamide. The study population is comprised of adults with mCRPC. Patients will self-administer NUV-422 and 160 mg enzalutamide orally in 28-day cycles. 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
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-02
• Last Update Posted: 2022-08-05
• Study Start: 2022-09
• Primary Completion: 2025-01
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: WITHDRAWN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

Inclusion Criteria

1. Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone

2. Have radiographic or biochemical evidence of progression as determined by Investigator per standard criteria

3. Have no known active or symptomatic central nervous system (CNS) disease

4. Prior therapy with abiraterone required and:

   • For Phase 1b only: up to 2 prior taxane-based chemotherapy regimens allowed for castration-resistant disease
   • For Phase 2 only: Patients must not have received prior taxane-based chemotherapy for castrate-resistant disease or prior treatment with CDK inhibitors

5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2

6. Adequate bone marrow and organ function

7. Eligible to receive enzalutamide

8. Life expectancy of > 6 months

Exclusion Criteria

1. History of seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma)

2. Have received chemotherapy, hormonal therapy (with the exception of ongoing LHRH analogs) radiation, or biological anti-cancer therapy within 14 days prior to first dose of NUV-422 and enzalutamide

3. Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent or 21 days (or < 5 half-lives) for myelosuppressive agent prior to the first dose of NUV-422 and enzalutamide

4. Requires medications that are known to be strong inducers and /or inhibitors of CYP3A4/5 enzymes, except enzalutamide

   • For Phase 1b only: Requires medications that are known to be moderate inducers and /or inhibitors of CYP3A4/5 enzymes, except enzalutamide

5. Prior therapy with enzalutamide, apalutamide, darolutamide, or investigational androgen receptor inhibitors

6. Known allergy or hypersensitivity to enzalutamide

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 enzalutamide until the recommended Phase 2 combination dose (RP2cD) is determined. 160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.
Phase 1b Dose Escalation	Enzalutamide	NUV-422 will be administered orally at escalating dose levels in combination with enzalutamide until the recommended Phase 2 combination dose (RP2cD) is determined. 160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.
Phase 2	NUV-422	NUV-422 will be administered orally at the RP2cD in combination with enzalutamide. 160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.
Phase 2	Enzalutamide	NUV-422 will be administered orally at the RP2cD in combination with enzalutamide. 160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-422.

Primary Outcome Measures

Name	Time	Method
Phase 2 Dose Expansion: Objective response rate (ORR)	Every 8 weeks throughout study treatment, an average of 6 months	ORR per standard criteria
Phase 1b Dose Escalation: Safety and tolerability of NUV-422 in combination with enzalutamide 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: Prostate-specific antigen (PSA)-response rate (PSA-RR)	Every 4 weeks throughout study treatment, an average of 6 months	PSA per standard criteria

Trial Locations

Locations (3)

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

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

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States