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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 : Terminated (Sponsor decision)
First Posted : September 9, 2020
Last Update Posted : October 4, 2022
Sponsor:
Information provided by (Responsible Party):
Nuvation Bio Inc.

Study Description
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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 Advanced Breast Cancer Advanced Breast Carcinoma Metastatic Breast Cancer Metastatic Breast Carcinoma Prostate Cancer Prostatic Cancer Cancer of Prostate Cancer of the Prostate Prostate Neoplasm Castrate Resistant Prostate Cancer Castration-resistant Prostate Cancer Castration Resistant Prostatic Neoplasms Glioblastoma Recurrent Glioblastoma Drug: NUV-422 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 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
Actual Primary Completion Date : August 31, 2022
Actual Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1 Dose Escalation
NUV-422 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached.
 Drug: NUV-422
NUV-422 is an investigational drug for oral dosing.
Experimental: Phase 2 Dose Expansion
NUV-422 will be administered at the recommended Phase 2 dose (RP2D).
 Drug: NUV-422
NUV-422 is an investigational drug for oral dosing.
Experimental: Phase 1 Surgical Substudy for Recurrent Glioblastoma

For subjects with pre-planned surgery per standard of care:

  • NUV-422 will be administered before surgery for the experimental group
  • No study treatment will be administered before surgery for the control group.

All patients will be offered NUV-422 post surgery and recovery, if deemed eligible.

 Drug: NUV-422
NUV-422 is an investigational drug for oral dosing.


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1 Dose Escalation: Safety and tolerability of NUV-422 to determine the recommended Phase 2 dose (RP2D) [ 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 1 Surgical Substudy (GB): Pharmacokinetic (PK) profile of NUV-422 [ Time Frame: Peri-operatively during surgery that is required per standard of care ]
    Concentration of NUV-422 and its metabolites in tumor tissue

  3. Phase 2 Dose Expansion Cohort 1 (IDH-WT GB): Objective Response [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    Objective response rate (ORR) per standard criteria and duration of response (DOR)

  4. Phase 2 Dose Expansion Cohort 2 (HR+HER2- mBC): Objective response [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR per standard criteria and DOR

  5. Phase 2 Dose Expansion Cohort 3 (mCRPC): Objective response [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR per standard criteria and DOR

  6. Phase 2 Dose Expansion Cohort 4 (HR+HER2- mBC with brain metastases): Objective response [ Time Frame: Every 8 weeks through study treatment, an average of 6 months ]
    ORR per standard criteria and DOR, for both brain metastases and breast cancer


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. Prior therapy: At least 1 but not more than 4 prior lines of systemic therapies for locally advanced inoperable or metastatic BC including at least 1 prior line of hormonal therapy in combination with an approved CDK4/6 inhibitor
  6. Have no known active or symptomatic central nervous system (CNS) disease
  7. 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. Evidence of disease progression as determined by 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 1 Surgical Substudy (Glioblastoma):

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

Phase 2 Expansion Cohort 1 (Glioblastoma):

  1. Histologically confirmed diagnosis of IDH-WT glioblastoma
  2. Received prior therapy with 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 (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 3 (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; patients without measurable disease must have PSA ≥ 2 ng/mL
  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 4 (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
  5. At least 1 measurable brain lesion per standard criteria

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
Contacts and Locations
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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


Locations
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United States, Arizona
Arizona Oncology Associates
Tucson, Arizona, United States, 85711
United States, Florida
Miami Cancer Institute
Miami, Florida, United States, 33176
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Carolina BioOncology Institute
Huntersville, North Carolina, United States, 28078
United States, South Carolina
Prisma Health Cancer Institute
Greenville, South Carolina, United States, 29605
United States, Texas
Texas Oncology P.A. Austin
Austin, Texas, United States, 78705
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Oncology
Tyler, Texas, United States, 75702
United States, Utah
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Nuvation Bio Inc.
More Information
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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: October 4, 2022
Last Verified: September 2022

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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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Carcinoma
Breast Neoplasms
Neoplasms
Prostatic Neoplasms
Glioblastoma
Glioma
Prostatic Neoplasms, Castration-Resistant
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Breast Diseases
 Skin Diseases
Disease Attributes
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Prostatic Diseases
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue