NUV-868-01 is a first-in human, open- label, Phase 1/2 dose escalation and expansion study in patients with advanced solid tumors. The Phase 1 and 1b portions include patients with advanced solid tumors and are designed to determine the safety and the dose(s) of NUV-868 to be used as monotherapy and in combination with olaparib or enzalutamide for the Phase 2 portion. In Phase 2, NUV-868 in combination with olaparib or enzalutamide will be given to determine the safety and efficacy of these study treatments. One cohort of patients (with enzalutamide-naïve metastatic castration-resistant prostate cancer) will be randomized to receive either NUV-868 monotherapy, enzalutamide monotherapy, or the combination of NUV-868 + enzalutamide. Patients will self-administer NUV-868 orally daily in 28-day cycles as monotherapy in Phases 1 and 2. In Phases 1b and 2, patients will self-administer NUV-868 orally daily in 28-day cycles in combination with olaparib or enzalutamide daily at standard prescribed doses (Phase 1b) or at the recommended Phase 2 combination dose (RP2cD) that is determined in Phase 1b. Patients will be treated until disease progression, toxicity, withdrawal of consent, or termination of the study.
This study was initially planned as a Phase 1/2 study; however, the study stopped early prior to the start of Phase 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
82
NUV-868 is an investigational drug for oral dosing.
Olaparib
Enzalutamide
The University of Arizona Cancer Center
Tucson, Arizona, United States
Ellison Institute of Technology
Los Angeles, California, United States
Rocky Mountain Cancer Centers, LLP
Aurora, Colorado, United States
Rocky Mountain Cancer Centers, LLP
Lone Tree, Colorado, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Laura & Isaac Perlmutter Cancer Center - NYU Langone Health
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
...and 12 more locations
Phase 1 Monotherapy Dose Escalation: Safety and tolerability of NUV-868 to determine the recommended Phase 2 dose (RP2D)
Incidence of dose-limiting toxicities (DLTs)
Time frame: During the DLT period (28 days)
Phase 1b Dose Escalation, NUV-868 + Olaparib: Safety and tolerability of NUV-868 in combination with olaparib to determine the recommended Phase 2 combination dose (RP2cD)
Incidence of DLTs
Time frame: During the DLT period (28 days)
Phase 1b Dose Escalation, NUV-868 + Olaparib: Pharmacokinetic (PK) profiles of NUV-868 and olaparib when administered in combination
NUV-868 and olaparib combination PK
Time frame: Days 1, 8, and 29
Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Safety and tolerability of NUV-868 in combination with enzalutamide to determine the RP2cD
Incidence of DLTs
Time frame: During the DLT period (28 days)
Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Pharmacokinetic (PK) profiles of NUV-868 and enzalutamide when administered in combination
NUV-868 and enzalutamide combination PK
Time frame: Days 1, 8, and 57
Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging
ORR per standard criteria
Time frame: Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
Phase 2, NUV-868 + Olaparib: Change from Baseline in PSA measurements
PSA50 response rate per standard criteria; only for patients with prostate cancer
Time frame: Every 4 weeks throughout study treatment, up to an average of 12 months (end of treatment)
Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Naïve Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Time from First Dose to Disease Progression
Radiographic progression-free survival (rPFS) per standard criteria
Time frame: Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Resistant mCRPC: Response to Study Treatment
Composite response rate (CRR: radiologic response, PSA50 response, and/or circulating tumor cell response) per standard criteria
Time frame: Every 4-12 weeks (time points vary depending on the type of response being evaluated) throughout study treatment, up to an average of 12 months (end of treatment)
Phase 1b Food Effect Substudy: Effect of Food on the Pharmacokinetics (PK) of NUV-868
NUV-868 PK parameters in fed and fasted states
Time frame: Pre dose and 24 hours after the first and second doses of NUV-868, 7 days apart
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.