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Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors

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ClinicalTrials.gov Identifier: NCT04541225
Recruitment Status : Recruiting
First Posted : September 9, 2020
Last Update Posted : July 20, 2021
Sponsor:
Information provided by (Responsible Party):
Nuvation Bio Inc.

Tracking Information
First Submitted Date  ICMJE August 21, 2020
First Posted Date  ICMJE September 9, 2020
Last Update Posted Date July 20, 2021
Actual Study Start Date  ICMJE December 8, 2020
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
  • Phase 1 Dose Escalation [ Time Frame: During the DLT period (28 days) ]
    Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
  • Phase 2 Dose Expansion Cohort 1 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    Objective response rate (ORR) and Duration of Response (DOR)
  • Phase 2 Dose Expansion Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 concentration in plasma, including peak plasma concentration
  • Phase 2 Dose Expansion Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 half-life in plasma
  • Phase 2 Dose Expansion Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 concentration in brain tumor tissue
  • Phase 2 Dose Expansion Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 effects on brain tumor cell proliferation ratio pre- and post-treatment
  • Phase 2 Dose Expansion Cohort 3 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR
  • Phase 2 Dose Expansion Cohort 3 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    DOR
  • Phase 2 Dose Expansion Cohort 4 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR
  • Phase 2 Dose Expansion Cohort 4 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    DOR
  • Phase 2 Dose Expansion Cohort 4 [ Time Frame: Every 4 weeks through study treatment, an average of 6 months ]
    Decrease in the prostate-specific antigen (PSA) pre- and post-treatment
  • Phase 2 Dose Expansion Cohort 5 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR
  • Phase 2 Dose Expansion Cohort 5 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    DOR
Original Primary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
  • Phase 1 Dose Escalation [ Time Frame: During the dose-limiting toxicity (DLT) period (28 days) ]
    Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs).
  • Phase 2 Dose Expansion: Cohort 1 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    Objective response rate (ORR)
  • Phase 2 Dose Expansion: Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 concentration in plasma, including peak plasma concentration (Cmax).
  • Phase 2 Dose Expansion: Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 half-life in plasma.
  • Phase 2 Dose Expansion: Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 concentration in brain tumor tissue.
  • Phase 2 Dose Expansion: Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 effects on brain tumor cell proliferation ratio pre and post-treatment.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors
Official Title  ICMJE Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors
Brief Summary NUV-422-02 is a first-in-human, open-label, Phase 1/2 dose escalation and multiple expansion cohort study designed to evaluate the safety and efficacy of NUV-422. The study population is comprised of adults with recurrent or refractory high-grade gliomas (HGGs), metastatic breast cancer (mBC), with and without brain metastases, and recurrent or refractory metastatic castration-resistant prostate cancer (mCRPC). All patients will self-administer NUV-422 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioma
  • Glioma, Malignant
  • Glioma, Mixed
  • Glial Cell Tumors
  • Breast Cancer
  • Breast Carcinoma
  • Cancer of Breast
  • Cancer of the Breast
  • Breast Tumor
  • Malignant Tumor of Breast
  • Prostate Cancer
  • Prostatic Cancer
  • Cancer of Prostate
  • Cancer of the Prostate
  • Prostate Neoplasm
Intervention  ICMJE Drug: NUV-422
NUV-422
Study Arms  ICMJE
  • Experimental: Phase 1 Dose Escalation
    NUV-422 administered at escalating dose levels until the maximum tolerated dose (MTD) is reached.
    Intervention: Drug: NUV-422
  • Experimental: Phase 2 Dose Expansion
    NUV-422 administered at the recommended Phase 2 dose (RP2D).
    Intervention: Drug: NUV-422
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2021)
218
Original Estimated Enrollment  ICMJE
 (submitted: September 1, 2020)
80
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

For All Phases and Cohorts:

  1. Recovered from toxicity to prior anti-cancer therapy
  2. Adequate bone marrow and organ function
  3. Appropriate candidate for NUV-422 monotherapy
  4. Life expectancy of > 3 months

Cohort-Specific Inclusion Criteria: In addition to the inclusion criteria listed above, the following criteria apply based on enrollment into specific cohorts.

Phase 1 (High-Grade Glioma):

  1. Histologically confirmed diagnosis of high-grade glioma
  2. Evidence of recurrence after treatment (ie, surgery, radiation, or temozolomide) or refractory (or intolerant) to treatment
  3. Measurable or non-measurable disease
  4. Karnofsky Performance Status (KPS) score ≥ 60

Phase 1 (HR+HER2- Metastatic Breast Cancer):

  1. Men and women who are not suitable for surgical resection or radiotherapy for the purpose of cure
  2. Diagnosis of locally advanced or HR+ HER2 metastatic breast cancer
  3. Evidence of progression as determined by the Investigator per standard criteria
  4. Patients must have endocrine-resistant disease.
  5. Have no known active or symptomatic central nervous system (CNS) disease
  6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2

Phase 1 (Metastatic Castration-Resistant Prostate Cancer):

  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 the Investigator per standard criteria
  3. Have no known active or symptomatic CNS disease
  4. Received prior therapy with anti-androgen(s) and taxane-based chemotherapy for castration-resistant disease
  5. ECOG PS ≤ 2

Phase 2 Expansion Cohort 1 (Glioblastoma):

  1. Histologically confirmed diagnosis of glioblastoma
  2. Received prior therapy with radiation or radiation plus temozolomide
  3. Radiographic evidence of progression and measurable disease as determined by the Investigator per standard criteria
  4. KPS score ≥ 70

Phase 2 Expansion Cohort 2 (Glioblastoma):

  1. Histologically confirmed diagnosis of glioblastoma
  2. Received prior therapy with radiation or radiation plus temozolomide
  3. Radiographic evidence of progression and measurable disease as determined by the Investigator per standard criteria
  4. KPS score ≥ 70
  5. Eligible for surgical resection

Phase 2 Expansion Cohort 3 (HR+HER2- Metastatic Breast Cancer):

  1. Men and women who are not suitable for surgical resection or radiotherapy for the purpose of cure
  2. Diagnosis of locally advanced or HR+HER2- metastatic breast cancer
  3. Evidence of progression and measurable disease as determined by the Investigator per standard criteria
  4. Have no known active or symptomatic CNS disease
  5. ECOG PS ≤ 2

Phase 2 Expansion Cohort 4 (Metastatic Castration-Resistant Prostate Cancer):

  1. Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone
  2. Have radiographic or biochemical evidence of progression and measurable disease as determined by the Investigator per standard criteria
  3. Have no known active or symptomatic CNS disease
  4. Received prior therapy with anti-androgen(s) and taxane-based chemotherapy for castration-resistant disease
  5. ECOG PS ≤ 2

Phase 2 Expansion Cohort 5 (HR+HER2- Metastatic Breast Cancer with brain metastases)

  1. Men and women who are not suitable for surgical resection or radiotherapy for the purpose of cure
  2. Diagnosis of HR+HER2- metastatic breast cancer with brain lesion(s)
  3. Evidence of progression and measurable disease as determined by the Investigator per standard criteria
  4. ECOG PS ≤ 2

Key Exclusion Criteria for All Phases and Cohorts:

  1. Have received chemotherapy, hormonal therapy (with the exception of ongoing LHRH analogs in male patients and premenopausal women), radiation, or biological anti-cancer therapy within 14 days prior to the first dose of NUV-422
  2. Has a history of or current use of bevacizumab (glioma and brain metastases only)
  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
  4. Requires systemic corticosteroid therapy > 4 mg/day (> 2 mg/day for Expansion Cohort 2) of dexamethasone or equivalent or increasing doses of systemic corticosteroids during the 7 days prior to enrollment
  5. Requires anti-seizure medications that are known to be strong inducers of CYP3A4/5 enzymes (carbamazepine, phenytoin) or has a recent history of uncontrolled or intermittent seizures
  6. Females who are pregnant or breast feeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials at Nuvation Bio 332-208-6102 ClinicalTrials@nuvationbio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04541225
Other Study ID Numbers  ICMJE NUV-422-02
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nuvation Bio Inc.
Study Sponsor  ICMJE Nuvation Bio Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Nuvation Bio Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP