Clinical trial NCT05191017: Study of NUV-422 in Combination With Enzalutamide in Patients With mCRPC
Official title: Phase 1b/2 Safety and Efficacy Study of NUV-422 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: 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
Keywords: Phase 1
Phase 2
metastatic castration-resistant prostate cancer
NUV-422
enzalutamide
Xtandi
CDK
CDK inhibition
CDK2/4/6
Lead sponsor: Nuvation Bio Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1b Dose Escalation: Safety and tolerability of NUV-422 in combination with enzalutamide to determine the recommended Phase 2 combination dose (RP2cD)
timeFrame: During the DLT period (28 days)
measure: Phase 2 Dose Expansion: Prostate-specific antigen (PSA)-response rate (PSA-RR)
timeFrame: Every 4 weeks throughout study treatment, an average of 6 months
measure: Phase 2 Dose Expansion: Objective response rate (ORR)
timeFrame: Every 8 weeks throughout study treatment, an average of 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Gettysburg
country: United States
facility: Pennsylvania Cancer Specialists and Research Institute
state: Pennsylvania
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
References: