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

Nuvation Bio

Status and phase: Terminated; Phase 1

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

Treatments: Drug: NUV-422

Study type: Interventional

Funder types: Industry

Identifiers

NCT04541225

NUV-422-02

Details and patient eligibility

About

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.

Enrollment: 74 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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74 participants in 1 patient group

Phase 1 Dose Escalation

Experimental group

Description:

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

Treatment:

Drug: NUV-422