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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04541225
• Other study ID #: NUV-422-02
• Status: Terminated
• Phase: Phase 1
• Start date: December 8, 2020
• Est. completion date: August 31, 2022

Study information

• Verified date: July 2023
• Source: Nuvation Bio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 74
• Est. completion date: August 31, 2022
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Advanced Breast Carcinoma
• Breast Cancer
• Breast Carcinoma
• Breast Neoplasms
• Breast Tumor
• Cancer of Breast
• Cancer of Prostate
• Cancer of the Breast
• Cancer of the Prostate
• Carcinoma
• Castrate Resistant Prostate Cancer
• Castration Resistant Prostatic Neoplasms
• Castration-resistant Prostate Cancer
• Glial Cell Tumors
• Glioblastoma
• Glioma
• Glioma, Malignant
• Glioma, Mixed
• Malignant Tumor of Breast
• Metastatic Breast Cancer
• Metastatic Breast Carcinoma
• Neoplasms
• Prostate Cancer
• Prostate Neoplasm
• Prostatic Cancer
• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant
• Recurrence
• Recurrent Glioblastoma

Intervention

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

Locations

Country	Name	City	State
United States	Texas Oncology P.A. Austin	Austin	Texas
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Prisma Health Cancer Institute	Greenville	South Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Miami Cancer Institute	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Texas Oncology	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Nuvation Bio Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Dose Escalation: Safety and tolerability of NUV-422 to determine the recommended Phase 2 dose (RP2D)	Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)	During the DLT period (28 days)