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Clinical Trial Record

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NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors

2022-03-29

2024-07-15

2024-07-15

82

Study Overview

NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors

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.

N/A

  • Advanced Solid Tumor
  • Ovarian Cancer
  • Ovary Cancer
  • Cancer of Ovary
  • Cancer of the Ovary
  • Ovary Neoplasm
  • Pancreatic Cancer
  • Pancreas Cancer
  • Cancer of Pancreas
  • Cancer of the Pancreas
  • Pancreas Neoplasm
  • 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
  • Triple-negative Breast Cancer
  • Triple Negative Breast Cancer
  • Triple Negative Breast Neoplasms
  • Breast Cancer
  • Breast Carcinoma
  • Cancer of Breast
  • Cancer of the Breast
  • Breast Tumor
  • DRUG: NUV-868
  • DRUG: Olaparib
  • DRUG: Enzalutamide
  • NUV-868-01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2022-01-28  

N/A  

2025-03-11  

2022-02-11  

N/A  

2025-03-12  

2022-02-23  

N/A  

2025-03  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Phase 1 Monotherapy

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

  • NUV-868 is an investigational drug for oral dosing.
EXPERIMENTAL: Phase 1b Combination: NUV-868 + Olaparib

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-868

  • NUV-868 is an investigational drug for oral dosing.

DRUG: Olaparib

  • Olaparib
EXPERIMENTAL: Phase 1b Combination: NUV-868 + Enzalutamide

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-868

  • NUV-868 is an investigational drug for oral dosing.

DRUG: Enzalutamide

  • Enzalutamide
EXPERIMENTAL: Phase 2 Combination: NUV-868 + Olaparib

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

DRUG: NUV-868

  • NUV-868 is an investigational drug for oral dosing.

DRUG: Olaparib

  • Olaparib
EXPERIMENTAL: Phase 2 Combination: NUV-868 + Enzalutamide

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

DRUG: NUV-868

  • NUV-868 is an investigational drug for oral dosing.

DRUG: Enzalutamide

  • Enzalutamide
EXPERIMENTAL: Phase 2: NUV-868 Monotherapy

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

DRUG: NUV-868

  • NUV-868 is an investigational drug for oral dosing.
ACTIVE_COMPARATOR: Phase 2: Enzalutamide Monotherapy

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

DRUG: Enzalutamide

  • Enzalutamide
Primary Outcome MeasuresMeasure DescriptionTime Frame
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 DLTsDuring the DLT period (28 days)
Phase 1b Dose Escalation, NUV-868 + Olaparib: Pharmacokinetic (PK) profiles of NUV-868 and olaparib when administered in combinationNUV-868 and olaparib combination PKDays 1, 8, and 29
Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Safety and tolerability of NUV-868 in combination with enzalutamide to determine the RP2cDIncidence of DLTsDuring the DLT period (28 days)
Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Pharmacokinetic (PK) profiles of NUV-868 and enzalutamide when administered in combinationNUV-868 and enzalutamide combination PKDays 1, 8, and 57
Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor ImagingORR per standard criteriaEvery 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 measurementsPSA50 response rate per standard criteria; only for patients with prostate cancerEvery 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 ProgressionRadiographic progression-free survival (rPFS) per standard criteriaEvery 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 TreatmentComposite response rate (CRR: radiologic response, PSA50 response, and/or circulating tumor cell response) per standard criteriaEvery 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-868NUV-868 PK parameters in fed and fasted statesPre dose and 24 hours after the first and second doses of NUV-868, 7 days apart
Secondary Outcome MeasuresMeasure DescriptionTime Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

    Key Inclusion Criteria For All Phases and Cohorts:
    1. Recovered from toxicity to prior anticancer therapy 2. Adequate bone marrow and organ function 3. No known active or symptomatic central nervous system (CNS) disease
    Cohort-Specific Inclusion Criteria: In addition to the inclusion criteria listed above, the following criteria apply for enrollment into specific cohorts.
    Phase 1 (NUV-868 Monotherapy)
    1. 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 2. Life expectancy of > 3 months 3. Eastern Cooperative Oncology Group Performance Status ≤ 2 4. Measurable or non-measurable disease
    Phase 1b (NUV-868 in Combination With Enzalutamide or Olaparib)
    1. Life expectancy of > 3 months 2. Eastern Cooperative Oncology Group Performance Status ≤ 2 3. (Select cohorts only) Measurable disease 4. 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. 5. One of the following tumor types:
    1. Ovarian: Platinum-resistant OR platinum-refractory high grade serous ovarian, fallopian, or primary peritoneal cancer in the relapsed setting 2. Pancreatic: Pancreatic ductal adenocarcinoma (PDAC) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting 3. Prostate: Histologically confirmed, metastatic adenocarcinoma of the prostate (adenocarcinoma/high grade carcinoma with neuroendocrine features is allowed) with progression on or after treatment with at least one NHT in the metastatic setting 4. Breast: Triple-negative breast cancer (TNBC) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting 5. Other advanced tumors (only Phase 1b dose escalation, NUV-868 + olaparib): the study Medical Monitor must approve enrollment. 6. For all tumor types: Patients will be allowed in the study regardless of their BRCA/HRR status.
    Phase 2
    1. Life expectancy of > 6 months 2. (Select cohorts only): At least one measurable lesion defined by standard criteria 3. Eastern Cooperative Oncology Group Performance Status ≤ 1 4. One of the following tumor types:
    1. Ovarian: Platinum-resistant or platinum- refractory high grade serous ovarian, fallopian, or primary peritoneal cancer in the relapsed setting 2. Pancreatic: Progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting 3. Prostate: Histologically confirmed, metastatic adenocarcinoma of the prostate (adenocarcinoma/high grade carcinoma with neuroendocrine features is allowed) with progression on or after treatment with at least one NHT in the metastatic setting 4. Breast: TNBC with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting
    Key Exclusion Criteria For All Phases and Cohorts:
    1. 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. 2. 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. 3. 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. 4. Female patients who are pregnant of breastfeeding.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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