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

Study Overview
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Brief Summary
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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.

Official Title
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Phase 1b/2 Safety and Efficacy Study of NUV-422 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Conditions
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Prostate Cancer, Prostatic Cancer, Cancer of Prostate, Cancer of the Prostate, Prostate Neoplasm, Castrate Resistant Prostate Cancer, Castration Resistant Prostatic Cancer, Castration Resistant Prostatic Neoplasms

Intervention / Treatment
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* Drug: NUV-422
* Drug: Enzalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone Have radiographic or biochemical evidence of progression as determined by Investigator per standard criteria Have no known active or symptomatic central nervous system (CNS) disease 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 Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2 Adequate bone marrow and organ function Eligible to receive enzalutamide Life expectancy of > 6 months Exclusion Criteria: History of seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma) 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 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 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 Prior therapy with enzalutamide, apalutamide, darolutamide, or investigational androgen receptor inhibitors Known allergy or hypersensitivity to enzalutamide

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b Dose Escalation<br>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. | Drug: NUV-422<br>* NUV-422 is an investigational drug for oral dosing.<br>Drug: Enzalutamide<br>* Enzalutamide<br>* Other names: Xtandi;|
| Experimental: Phase 2<br>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. | Drug: NUV-422<br>* NUV-422 is an investigational drug for oral dosing.<br>Drug: Enzalutamide<br>* Enzalutamide<br>* Other names: Xtandi;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Phase 2, metastatic castration-resistant prostate cancer, NUV-422, enzalutamide, Xtandi, CDK, CDK inhibition, CDK2/4/6