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

• ClinicalTrials.gov Identifier: NCT04541225
• Recruitment Status: Terminated
• First Posted: September 9, 2020
• Last Update Posted: July 14, 2023
• Sponsor: Nuvation Bio Inc.
• Information provided by (Responsible Party): Nuvation Bio Inc.

Tracking Information

• First Submitted Date: August 21, 2020
• First Posted Date: September 9, 2020
• Last Update Posted Date: July 14, 2023
• Actual Study Start Date: December 8, 2020
• Actual Primary Completion Date: August 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2023)

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)

Original Primary Outcome Measures (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.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors
• 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
• Brief Summary: At the time of study termination, NUV-422-02 was a first-in-human, open-label, Phase 1 dose escalation study designed to evaluate the safety and efficacy of NUV-422. The study population comprised 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 self-administered 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

Drug: NUV-422

NUV-422 is an investigational drug for oral dosing.

Study Arms

Experimental: Phase 1 Dose Escalation

NUV-422 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached.

Intervention: Drug: NUV-422

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 12, 2023): 74
• Original Estimated Enrollment (submitted: September 1, 2020): 80
• Actual Study Completion Date: August 31, 2022
• Actual Primary Completion Date: August 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria

For All 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.

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

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

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

Key Exclusion Criteria for All 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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04541225
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Nuvation Bio Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Nuvation Bio Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Nuvation Bio Inc.
• Verification Date: July 2023