NCT05252390

Brief Summary

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Mar 2022

Typical duration for phase_1

Geographic Reach
2 countries

22 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 28, 2022

Completed
26 days until next milestone

First Posted

Study publicly available on registry

February 23, 2022

Completed
1 month until next milestone

Study Start

First participant enrolled

March 29, 2022

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 15, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 15, 2024

Completed
Last Updated

November 6, 2025

Status Verified

November 1, 2025

Enrollment Period

2.3 years

First QC Date

January 28, 2022

Last Update Submit

November 4, 2025

Conditions

Keywords

Phase 1Phase 2NUV-868olaparibenzalutamideXtandiovarian cancerpancreatic cancermetastatic castration-resistant prostate cancertriple-negative breast cancerLynparzaPARP inhibitorBET inhibitorBRCA mutationBRCA1BRCA2HRDHRR deficiencyhomologous recombination deficiency

Outcome Measures

Primary Outcomes (10)

  • 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)

    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

    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

    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

    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

    Days 1, 8, and 57

  • Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging

    ORR per standard criteria

    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

    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

    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

    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

    Pre dose and 24 hours after the first and second doses of NUV-868, 7 days apart

Study Arms (7)

Phase 1 Monotherapy

EXPERIMENTAL

NUV-868 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached or a recommended Phase 2 dose (RP2D) is determined.

Drug: NUV-868

Phase 1b Combination: NUV-868 + Olaparib

EXPERIMENTAL

NUV-868 will be administered at escalating dose levels in combination with olaparib until the recommended Phase 2 combination dose (RP2cD) is determined. 300 mg olaparib will be administered orally twice daily throughout the 28-day cycles of NUV-868.

Drug: NUV-868Drug: Olaparib

Phase 1b Combination: NUV-868 + Enzalutamide

EXPERIMENTAL

NUV-868 will be administered daily at escalating dose levels in combination with enzalutamide until the RP2cD is determined. 160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-868.

Drug: NUV-868Drug: Enzalutamide

Phase 2 Combination: NUV-868 + Olaparib

EXPERIMENTAL

NUV-868 will be administered at the RP2cD. Olaparib will be administered at the RP2cD.

Drug: NUV-868Drug: Olaparib

Phase 2 Combination: NUV-868 + Enzalutamide

EXPERIMENTAL

NUV-868 will be administered at the RP2cD. Enzalutamide will be administered at the RP2cD.

Drug: NUV-868Drug: Enzalutamide

Phase 2: NUV-868 Monotherapy

EXPERIMENTAL

NUV-868 will be administered at the RP2D in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.

Drug: NUV-868

Phase 2: Enzalutamide Monotherapy

ACTIVE COMPARATOR

160 mg enzalutamide will be administered orally daily in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.

Drug: Enzalutamide

Interventions

NUV-868 is an investigational drug for oral dosing.

Phase 1 MonotherapyPhase 1b Combination: NUV-868 + EnzalutamidePhase 1b Combination: NUV-868 + OlaparibPhase 2 Combination: NUV-868 + EnzalutamidePhase 2 Combination: NUV-868 + OlaparibPhase 2: NUV-868 Monotherapy

Olaparib

Also known as: Lynparza
Phase 1b Combination: NUV-868 + OlaparibPhase 2 Combination: NUV-868 + Olaparib

Enzalutamide

Also known as: Xtandi
Phase 1b Combination: NUV-868 + EnzalutamidePhase 2 Combination: NUV-868 + EnzalutamidePhase 2: Enzalutamide Monotherapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Recovered from toxicity to prior anticancer therapy
  • Adequate bone marrow and organ function
  • No known active or symptomatic central nervous system (CNS) disease
  • Phase 1 (NUV-868 Monotherapy)
  • Patients with advanced solid tumors that have progressed during or after treatment with approved therapies or for which there is no standard effective therapy available
  • Life expectancy of \> 3 months
  • Eastern Cooperative Oncology Group Performance Status ≤ 2
  • Measurable or non-measurable disease
  • Phase 1b (NUV-868 in Combination With Enzalutamide or Olaparib)
  • Life expectancy of \> 3 months
  • Eastern Cooperative Oncology Group Performance Status ≤ 2
  • (Select cohorts only) Measurable disease
  • Patient must be able to read and write sufficiently to document food intake and study drug dosing on the Dosing Diary or must have a caregiver who is willing and able to complete the Dosing Diary with the patient.
  • One of the following tumor types:
  • Ovarian: Platinum-resistant OR platinum-refractory high grade serous ovarian, fallopian, or primary peritoneal cancer in the relapsed setting
  • +14 more criteria

You may not qualify if:

  • Have received chemotherapy, hormonal therapy (except for ongoing luteinizing hormone-releasing hormone \[LHRH\] analogs in male patients and premenopausal women), radiation, or biological anticancer therapy within 14 days prior to the first dose of NUV-868.
  • Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent, or within 21 days or \< 5 half-lives (whichever is longer) for myelosuppressive agent, prior to the first dose of study treatment.
  • Requires medications that are known to be strong (or moderate for olaparib) inducers and/or strong (or moderate for olaparib) inhibitors of CYP3A4/5 enzymes.
  • Female patients who are pregnant of breastfeeding.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Ellison Institute of Technology

Los Angeles, California, 90064, United States

Location

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, 80012, United States

Location

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, 80124, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Laura & Isaac Perlmutter Cancer Center - NYU Langone Health

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, 76104, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Macquarie University Hospital

North Ryde, New South Wales, 2109, Australia

Location

Calvary Mater Hospital Newcastle

Waratah, New South Wales, 2298, Australia

Location

Cabrini Hospital Malvern

Malvern, Victoria, 3144, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Ovarian NeoplasmsPancreatic NeoplasmsProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantTriple Negative Breast NeoplasmsBreast Neoplasms

Interventions

olaparibenzalutamide

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersDigestive System NeoplasmsDigestive System DiseasesPancreatic DiseasesGenital Neoplasms, MaleGenital Diseases, MaleProstatic DiseasesMale Urogenital DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Sequential assignment will be applied in Phase 1 and Phase 1 b dose escalation cohorts. Parallel assignment will be applied in Phase 1b backfill cohorts and Phase 2.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 28, 2022

First Posted

February 23, 2022

Study Start

March 29, 2022

Primary Completion

July 15, 2024

Study Completion

July 15, 2024

Last Updated

November 6, 2025

Record last verified: 2025-11

Locations