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NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT05252390
Recruitment Status : Recruiting
First Posted : February 23, 2022
Last Update Posted : October 23, 2023
Sponsor:
Information provided by (Responsible Party):
Nuvation Bio Inc.

Study Description
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Brief Summary:
NUV-868-01 is a first-in human, open- label, Phase 1/2 dose escalation and expansion study in patients with advanced solid tumors. The Phase 1 and 1b portions include patients with advanced solid tumors and are designed to determine the safety and the dose(s) of NUV-868 to be used as monotherapy and in combination with olaparib or enzalutamide for the Phase 2 portion. In Phase 2, NUV-868 in combination with olaparib or enzalutamide will be given to determine the safety and efficacy of these study treatments. One cohort of patients (with enzalutamide-naïve metastatic castration-resistant prostate cancer) will be randomized to receive either NUV-868 monotherapy, enzalutamide monotherapy, or the combination of NUV-868 + enzalutamide. Patients will self-administer NUV-868 orally daily in 28-day cycles as monotherapy in Phases 1 and 2. In Phases 1b and 2, patients will self-administer NUV-868 orally daily in 28-day cycles in combination with olaparib or enzalutamide daily at standard prescribed doses (Phase 1b) or at the recommended Phase 2 combination dose (RP2cD) that is determined in Phase 1b. Patients will be treated until disease progression, toxicity, withdrawal of consent, or termination of the study.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Ovarian Cancer Ovary Cancer Cancer of Ovary Cancer of the Ovary Ovary Neoplasm Pancreatic Cancer Pancreas Cancer Cancer of Pancreas Cancer of the Pancreas Pancreas Neoplasm Prostate Cancer Prostatic Cancer Cancer of Prostate Cancer of the Prostate Prostate Neoplasm Castrate Resistant Prostate Cancer Castration Resistant Prostatic Cancer Castration Resistant Prostatic Neoplasms Triple-negative Breast Cancer Triple Negative Breast Cancer Triple Negative Breast Neoplasms Breast Cancer Breast Carcinoma Cancer of Breast Cancer of the Breast Breast Tumor Drug: NUV-868 Drug: Olaparib Drug: Enzalutamide Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 657 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Sequential assignment will be applied in Phase 1 and Phase 1 b dose escalation cohorts. Parallel assignment will be applied in Phase 1b backfill cohorts and Phase 2.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Safety and Efficacy Study of NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors
Actual Study Start Date : March 29, 2022
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : November 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1 Monotherapy
NUV-868 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached or a recommended Phase 2 dose (RP2D) is determined.
 Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.
Experimental: Phase 1b Combination: NUV-868 + Olaparib

NUV-868 will be administered at escalating dose levels in combination with olaparib until the recommended Phase 2 combination dose (RP2cD) is determined.

300 mg olaparib will be administered orally twice daily throughout the 28-day cycles of NUV-868.

 Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.

Drug: Olaparib
Olaparib
Other Name: Lynparza
Experimental: Phase 1b Combination: NUV-868 + Enzalutamide

NUV-868 will be administered daily at escalating dose levels in combination with enzalutamide until the RP2cD is determined.

160 mg enzalutamide will be administered orally daily throughout the 28-day cycles of NUV-868.

 Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.

Drug: Enzalutamide
Enzalutamide
Other Name: Xtandi
Experimental: Phase 2 Combination: NUV-868 + Olaparib

NUV-868 will be administered at the RP2cD.

Olaparib will be administered at the RP2cD.

 Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.

Drug: Olaparib
Olaparib
Other Name: Lynparza
Experimental: Phase 2 Combination: NUV-868 + Enzalutamide

NUV-868 will be administered at the RP2cD.

Enzalutamide will be administered at the RP2cD.

 Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.

Drug: Enzalutamide
Enzalutamide
Other Name: Xtandi
Experimental: Phase 2: NUV-868 Monotherapy
NUV-868 will be administered at the RP2D in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.
 Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.
Active Comparator: Phase 2: Enzalutamide Monotherapy
160 mg enzalutamide will be administered orally daily in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.
 Drug: Enzalutamide
Enzalutamide
Other Name: Xtandi


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1 Monotherapy Dose Escalation: Safety and tolerability of NUV-868 to determine the recommended Phase 2 dose (RP2D) [ Time Frame: During the DLT period (28 days) ]
    Incidence of dose-limiting toxicities (DLTs)

  2. Phase 1b Dose Escalation, NUV-868 + Olaparib: Safety and tolerability of NUV-868 in combination with olaparib to determine the recommended Phase 2 combination dose (RP2cD) [ Time Frame: During the DLT period (28 days) ]
    Incidence of DLTs

  3. Phase 1b Dose Escalation, NUV-868 + Olaparib: Pharmacokinetic (PK) profiles of NUV-868 and olaparib when administered in combination [ Time Frame: Days 1, 8, and 29 ]
    NUV-868 and olaparib combination PK

  4. Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Safety and tolerability of NUV-868 in combination with enzalutamide to determine the RP2cD [ Time Frame: During the DLT period (28 days) ]
    Incidence of DLTs

  5. Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Pharmacokinetic (PK) profiles of NUV-868 and enzalutamide when administered in combination [ Time Frame: Days 1, 8, and 57 ]
    NUV-868 and enzalutamide combination PK

  6. Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging [ Time Frame: Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment) ]
    ORR per standard criteria

  7. Phase 2, NUV-868 + Olaparib: Change from Baseline in PSA measurements [ Time Frame: Every 4 weeks throughout study treatment, up to an average of 12 months (end of treatment) ]
    PSA50 response rate per standard criteria; only for patients with prostate cancer

  8. Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Naïve Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Time from First Dose to Disease Progression [ Time Frame: Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment) ]
    Radiographic progression-free survival (rPFS) per standard criteria

  9. Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Resistant mCRPC: Response to Study Treatment [ Time Frame: Every 4-12 weeks (time points vary depending on the type of response being evaluated) throughout study treatment, up to an average of 12 months (end of treatment) ]
    Composite response rate (CRR: radiologic response, PSA50 response, and/or circulating tumor cell response) per standard criteria

  10. Phase 1b Food Effect Substudy: Effect of Food on the Pharmacokinetics (PK) of NUV-868 [ Time Frame: Pre dose and 24 hours after the first and second doses of NUV-868, 7 days apart ]
    NUV-868 PK parameters in fed and fasted states


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria For All Phases and Cohorts:

  1. Recovered from toxicity to prior anticancer therapy
  2. Adequate bone marrow and organ function
  3. No known active or symptomatic central nervous system (CNS) disease

Cohort-Specific Inclusion Criteria: In addition to the inclusion criteria listed above, the following criteria apply for enrollment into specific cohorts.

Phase 1 (NUV-868 Monotherapy)

  1. Patients with advanced solid tumors that have progressed during or after treatment with approved therapies or for which there is no standard effective therapy available
  2. Life expectancy of > 3 months
  3. Eastern Cooperative Oncology Group Performance Status ≤ 2
  4. Measurable or non-measurable disease

Phase 1b (NUV-868 in Combination With Enzalutamide or Olaparib)

  1. Life expectancy of > 3 months
  2. Eastern Cooperative Oncology Group Performance Status ≤ 2
  3. (Select cohorts only) Measurable disease
  4. Patient must be able to read and write sufficiently to document food intake and study drug dosing on the Dosing Diary or must have a caregiver who is willing and able to complete the Dosing Diary with the patient.

  5. One of the following tumor types:

    1. Ovarian: Platinum-resistant OR platinum-refractory high grade serous ovarian, fallopian, or primary peritoneal cancer in the relapsed setting
    2. Pancreatic: Pancreatic ductal adenocarcinoma (PDAC) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting
    3. Prostate: Histologically confirmed, metastatic adenocarcinoma of the prostate (adenocarcinoma/high grade carcinoma with neuroendocrine features is allowed) with progression on or after treatment with at least one NHT in the metastatic setting
    4. Breast: Triple-negative breast cancer (TNBC) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting
    5. Other advanced tumors (only Phase 1b dose escalation, NUV-868 + olaparib): the study Medical Monitor must approve enrollment.
    6. For all tumor types: Patients will be allowed in the study regardless of their BRCA/HRR status.

Phase 2

  1. Life expectancy of > 6 months
  2. (Select cohorts only): At least one measurable lesion defined by standard criteria
  3. Eastern Cooperative Oncology Group Performance Status ≤ 1

  4. One of the following tumor types:

    1. Ovarian: Platinum-resistant or platinum- refractory high grade serous ovarian, fallopian, or primary peritoneal cancer in the relapsed setting
    2. Pancreatic: Progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting
    3. Prostate: Histologically confirmed, metastatic adenocarcinoma of the prostate (adenocarcinoma/high grade carcinoma with neuroendocrine features is allowed) with progression on or after treatment with at least one NHT in the metastatic setting
    4. Breast: TNBC with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting

Key Exclusion Criteria For All Phases and Cohorts:

  1. Have received chemotherapy, hormonal therapy (except for ongoing luteinizing hormone-releasing hormone [LHRH] analogs in male patients and premenopausal women), radiation, or biological anticancer therapy within 14 days prior to the first dose of NUV-868.
  2. Received treatment with an investigational agent for any indication within 14 days for non-myelosuppressive agent, or within 21 days or < 5 half-lives (whichever is longer) for myelosuppressive agent, prior to the first dose of study treatment.
  3. Requires medications that are known to be strong (or moderate for olaparib) inducers and/or strong (or moderate for olaparib) inhibitors of CYP3A4/5 enzymes.
  4. Female patients who are pregnant of breastfeeding.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05252390


Contacts
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Contact: Elligo Health Research 833-686-5303 nuvationbio@elligodirect.com

Locations
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Sponsors and Collaborators
Nuvation Bio Inc.
More Information
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Responsible Party: Nuvation Bio Inc.
ClinicalTrials.gov Identifier: NCT05252390    
Other Study ID Numbers: NUV-868-01
First Posted: February 23, 2022    Key Record Dates
Last Update Posted: October 23, 2023
Last Verified: October 2023

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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
NUV-868
olaparib
enzalutamide
Xtandi
ovarian cancer
pancreatic cancer
metastatic castration-resistant prostate cancer
triple-negative breast cancer
 Lynparza
PARP inhibitor
BET inhibitor
BRCA mutation
BRCA1
BRCA2
HRD
HRR deficiency
homologous recombination deficiency
Additional relevant MeSH terms:
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Neoplasms
Breast Neoplasms
Prostatic Neoplasms
Pancreatic Neoplasms
Ovarian Neoplasms
Triple Negative Breast Neoplasms
Prostatic Neoplasms, Castration-Resistant
Neoplasms by Site
Breast Diseases
Skin Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
 Prostatic Diseases
Male Urogenital Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Genital Neoplasms, Female
Gonadal Disorders
Olaparib