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

Sponsor
Nuvation Bio Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04541225
Collaborator
(none)
269
Enrollment
12
Locations
3
Arms
35.7
Anticipated Duration (Months)
22.4
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

NUV-422-02 is a first-in-human, open-label, Phase 1/2 dose escalation and multiple expansion cohort study designed to evaluate the safety and efficacy of NUV-422. The study population is comprised of 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 will self-administer NUV-422 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
269 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 8, 2020
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1 Dose Escalation

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

Drug: NUV-422
NUV-422 is an investigational drug for oral dosing.
Experimental: Phase 2 Dose Expansion

NUV-422 will be administered at the recommended Phase 2 dose (RP2D).

Drug: NUV-422
NUV-422 is an investigational drug for oral dosing.
Experimental: Phase 1 Surgical Substudy for Recurrent Glioblastoma

For subjects with pre-planned surgery per standard of care: NUV-422 will be administered before surgery for the experimental group No study treatment will be administered before surgery for the control group. All patients will be offered NUV-422 post surgery and recovery, if deemed eligible.

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

Outcome Measures

Primary Outcome Measures

  1. 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)

  2. Phase 1 Surgical Substudy (GB): Pharmacokinetic (PK) profile of NUV-422 [Peri-operatively during surgery that is required per standard of care]

    Concentration of NUV-422 and its metabolites in tumor tissue

  3. Phase 2 Dose Expansion Cohort 1 (IDH-WT GB): Objective Response [Every 8 weeks through study treatment, an average of 6 months]

    Objective response rate (ORR) per standard criteria and duration of response (DOR)

  4. Phase 2 Dose Expansion Cohort 2 (HR+HER2- mBC): Objective response [Every 8 weeks through study treatment, an average of 6 months]

    ORR per standard criteria and DOR

  5. Phase 2 Dose Expansion Cohort 3 (mCRPC): Objective response [Every 8 weeks through study treatment, an average of 6 months]

    ORR per standard criteria and DOR

  6. Phase 2 Dose Expansion Cohort 4 (HR+HER2- mBC with brain metastases): Objective response [Every 8 weeks through study treatment, an average of 6 months]

    ORR per standard criteria and DOR, for both brain metastases and breast cancer

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Key Inclusion Criteria

For All Phases and 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.

Phase 1 (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

Phase 1 (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

Phase 1 (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

Phase 1 Surgical Substudy (Glioblastoma):

  1. Histologically confirmed diagnosis of glioblastoma

  2. Received prior therapy with radiation or radiation plus temozolomide

  3. Radiographic evidence of progression as determined by the Investigator per standard criteria

  4. KPS score ≥ 70

  5. Eligible for surgical resection

Phase 2 Expansion Cohort 1 (Glioblastoma):

  1. Histologically confirmed diagnosis of IDH-WT glioblastoma

  2. Received prior therapy with radiation plus temozolomide

  3. Radiographic evidence of progression and measurable disease as determined by the Investigator per standard criteria

  4. KPS score ≥ 70

Phase 2 Expansion Cohort 2 (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 and measurable disease as determined by the Investigator per standard criteria

  4. Have no known active or symptomatic CNS disease

  5. ECOG PS ≤ 2

Phase 2 Expansion Cohort 3 (Metastatic Castration-Resistant Prostate Cancer):

  1. Diagnosis of metastatic castration-resistant prostate cancer with disease progression despite castrate levels of testosterone

  2. Have radiographic or biochemical evidence of progression and measurable disease as determined by the Investigator per standard criteria; patients without measurable disease must have PSA ≥ 2 ng/mL

  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

Phase 2 Expansion Cohort 4 (HR+HER2- Metastatic Breast Cancer with Brain Metastases):

  1. Men and women who are not suitable for surgical resection or radiotherapy for the purpose of cure

  2. Diagnosis of HR+HER2- metastatic breast cancer with brain lesion(s)

  3. Evidence of progression and measurable disease as determined by the Investigator per standard criteria

  4. ECOG PS ≤ 2

  5. At least 1 measurable brain lesion per standard criteria

Key Exclusion Criteria (for All Phases and 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

  1. of dexamethasone or equivalent or increasing doses of systemic corticosteroids during the 7 days prior to enrollment

  1. 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

  2. Females who are pregnant or breast feeding

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arizona Oncology Associates Tucson Arizona United States 85711
2 Miami Cancer Institute Miami Florida United States 33176
3 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
4 Memorial Sloan Kettering Cancer Center New York New York United States 10065
5 Carolina BioOncology Institute Huntersville North Carolina United States 28078
6 Prisma Health Cancer Institute Greenville South Carolina United States 29605
7 Texas Oncology P.A. Austin Austin Texas United States 78705
8 Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
9 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
10 Texas Oncology Tyler Texas United States 75702
11 University of Utah Huntsman Cancer Institute Salt Lake City Utah United States 84112
12 Virginia Cancer Specialists Fairfax Virginia United States 22031

Sponsors and Collaborators

  • Nuvation Bio Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Nuvation Bio Inc.
ClinicalTrials.gov Identifier:
NCT04541225
Other Study ID Numbers:
  • NUV-422-02
First Posted:
Sep 9, 2020
Last Update Posted:
Jun 30, 2022
Last Verified:
Jun 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Nuvation Bio Inc.
Phase 1
Phase 2
malignant glioma
metastatic breast cancer
metastatic castration-resistant prostate cancer
Additional relevant MeSH terms:
Carcinoma
Breast Neoplasms
Neoplasms
Prostatic Neoplasms
Glioblastoma
Glioma
Prostatic Neoplasms, Castration-Resistant
Recurrence

Study Results

No Results Posted as of Jun 30, 2022