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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.

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.

Condition or disease Intervention/treatment Phase
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 Drug: NUV-422 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 218 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 8, 2020
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 Dose Escalation
NUV-422 administered at escalating dose levels until the maximum tolerated dose (MTD) is reached.
Drug: NUV-422
NUV-422

Experimental: Phase 2 Dose Expansion
NUV-422 administered at the recommended Phase 2 dose (RP2D).
Drug: NUV-422
NUV-422




Primary Outcome Measures :
  1. 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)

  2. 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)

  3. 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

  4. Phase 2 Dose Expansion Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 half-life in plasma

  5. Phase 2 Dose Expansion Cohort 2 [ Time Frame: Intraoperatively after 21 days of study treatment ]
    Evaluation of NUV-422 concentration in brain tumor tissue

  6. 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

  7. Phase 2 Dose Expansion Cohort 3 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR

  8. Phase 2 Dose Expansion Cohort 3 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    DOR

  9. Phase 2 Dose Expansion Cohort 4 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR

  10. Phase 2 Dose Expansion Cohort 4 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    DOR

  11. 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

  12. Phase 2 Dose Expansion Cohort 5 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR

  13. Phase 2 Dose Expansion Cohort 5 [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    DOR



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04541225


Contacts
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Contact: Clinical Trials at Nuvation Bio 332-208-6102 ClinicalTrials@nuvationbio.com

Locations
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United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Patrick Y Wen, MD    617-632-2166      
Contact: Rachel Fox    617-632-6668      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Thomas Kaley, MD    212-639-5122      
Contact: Christine Jarjies    646-907-2567      
United States, North Carolina
Carolina BioOncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Ashley McClain    980-441-1021    AMcClain@carolinabiooncology.org   
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jordi Rodon, MD, PhD    713-563-1930      
United States, Utah
University of Utah Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Howard Colman, MD    801-585-0255    Howard.Colman@hci.utah.edu   
Contact: Sara Woltz    801-585-0431    Sara.Woltz@hci.utah.edu   
Sponsors and Collaborators
Nuvation Bio Inc.
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Responsible Party: Nuvation Bio Inc.
ClinicalTrials.gov Identifier: NCT04541225    
Other Study ID Numbers: NUV-422-02
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nuvation Bio Inc.:
Phase 1
Phase 2
malignant glioma
metastatic breast cancer
metastatic castration-resistant prostate cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms
Prostatic Neoplasms
Glioma
Neoplasms by Site
Breast Diseases
Skin Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Prostatic Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue