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

Phase 1

Terminated

• Conditions: Cancer of Breast; Prostatic Cancer; Castrate Resistant Prostate Cancer; Recurrent Glioblastoma; Glial Cell Tumors; Malignant Tumor of Breast; Glioma, Malignant; Glioma, Mixed; Prostate Cancer; Cancer of the Prostate
• Interventions: Drug: NUV-422

• Registration Number: NCT04541225
• Lead Sponsor: Nuvation Bio Inc.

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 available

Study Timeline

• Study First Submitted: 2020-08-21
• Study First Submitted QC: 2020-09-01
• Study First Posted: 2020-09-09
• Study Start: 2020-12-08
• Primary Completion: 2022-08-31
• Study Completion: 2022-08-31
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-12
• Last Update Posted: 2023-07-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 74

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1 Dose Escalation	NUV-422	NUV-422 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached.

Primary Outcome Measures

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

Trial Locations

Locations (12)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

Texas Oncology P.A. Austin; 🇺🇸 Austin, Texas, United States

Texas Oncology; 🇺🇸 Tyler, Texas, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Miami Cancer Institute; 🇺🇸 Miami, Florida, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

Prisma Health Cancer Institute; 🇺🇸 Greenville, South Carolina, United States

Arizona Oncology Associates; 🇺🇸 Tucson, Arizona, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

University of Utah Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States