Clinical trial NCT04541225: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Keywords: Phase 1
malignant glioma
metastatic breast cancer
metastatic castration-resistant prostate cancer
Lead sponsor: Nuvation Bio Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-09
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Phase 1 Dose Escalation: Safety and tolerability of NUV-422 to determine the recommended Phase 2 dose (RP2D)
timeFrame: During the DLT period (28 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology P.A. Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
References: