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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 4, 2022
Sponsor:
Information provided by (Responsible Party):
Nuvation Bio Inc.

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 of NUV-868 to be used as monotherapy and in combination with olaparib or enzalutamide for the Phase 2 and 2b portions. In these Phase 2 portions, NUV-868 as a monotherapy (Phase 2) or in combination with olaparib or enzalutamide (Phase 2b) will be given to determine the safety and efficacy of these study treatments. Patients will self-administer NUV-868 orally daily in 28-day cycles as monotherapy in Phases 1 and 2. In Phases 1b and 2b, patients will self-administer NUV-868 orally daily in 28-day cycles with either 300 mg olaparib twice daily or 160 mg enzalutamide daily. 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 246 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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 : January 2026
Estimated Study Completion Date : February 2026


Arm Intervention/treatment
Experimental: Phase 1 Monotherapy Dose Escalation
NUV-868 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached.
Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.

Experimental: Phase 1b Dose Escalation: 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 Dose Escalation: 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 Monotherapy Expansion
NUV-868 will be administered at the RP2D.
Drug: NUV-868
NUV-868 is an investigational drug for oral dosing.

Experimental: Phase 2b Combination Expansion: NUV-868 + Olaparib

NUV-868 will be administered at the RP2cD.

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 2b Combination Expansion: NUV-868 + Enzalutamide

NUV-868 will be administered at the RP2cD.

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




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: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 2 Day 1 (each cycle is 28 days) ]
    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: Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 3 Day 1 (each cycle is 28 days) ]
    NUV-868 and enzalutamide combination PK

  6. Phase 2 Monotherapy Expansion: Change from Baseline in Tumor Imaging [ Time Frame: Every 8 weeks starting at Cycle 3 Day 1 (each cycle is 28 days), up to an average of 12 months (end of treatment) ]
    Overall Response Rate (ORR) per standard criteria

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

  8. Phase 2b Combination Expansion, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging [ Time Frame: Every 8 weeks starting at Cycle 3 Day 1 (each cycle is 28 days), up to an average of 12 months (end of treatment) ]
    ORR per standard criteria

  9. Phase 2b Combination Expansion, 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) ]
    PSA-RR per standard criteria; only for patients with prostate cancer

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



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

Inclusion Criteria For All Phases and Cohorts:

  1. Recovered from toxicity to prior anti-cancer therapy
  2. Adequate bone marrow and organ function
  3. Have 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 (Monotherapy Study; Advanced Solid Tumors)

  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 (Combination Study with Enzalutamide or Olaparib)

  1. Life expectancy of > 3 months
  2. Eastern Cooperative Oncology Group Performance Status ≤ 2
  3. Measurable or non-measurable disease
  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. Patients with BRCA mutation or who are otherwise positive for homologous recombination deficiency must have received prior treatment with a PARP inhibitor.
    2. Pancreatic: Progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting. Patients with BRCA mutation must have received prior treatment with a PARP inhibitor.
    3. Prostate: mCRPC with progression on or after treatment with at least one androgen receptor-directed therapy. Patients with HRR gene mutation must have received prior treatment with a PARP inhibitor.
    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. Patients with BRCA mutation must have received prior treatment with a PARP inhibitor.
    5. For all tumor types: Patients will be allowed in the study regardless of their BRCA/HRR status.

Phase 2 (Monotherapy Study) and Phase 2b (Combination Study with Enzalutamide or Olaparib)

  1. Life expectancy of > 6 months
  2. Phase 2b (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. Patients with BRCA mutation or who are otherwise positive for homologous recombination deficiency must have received prior treatment with a PARP inhibitor.
    2. Pancreatic: Progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting. Patients with BRCA mutation must have received prior treatment with a PARP inhibitor.
    3. Prostate:

      • Phase 2 Monotherapy Only: mCRPC with progression on or after treatment with at least one androgen receptor (AR)-directed therapy, and at least one prior treatment with taxane chemotherapy for castration-resistant disease.
      • Phase 2b Combination Only: mCRPC with progression on or after treatment with at least one AR-directed therapy, and no prior taxane chemotherapy for castration-resistant disease. Patients with a deleterious or suspected deleterious germline or somatic HRR gene mutation must have received prior treatment with a PARP inhibitor.
    4. Breast: TNBC with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting. Patients with BRCA mutation must have received prior treatment with a PARP inhibitor.
    5. For all tumor types: Patients will be allowed in the study regardless of their BRCA/HRR status.

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 anti-cancer 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 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

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

Phase 1b, for the combination of NUV-868 + enzalutamide only

  1. Requires medications that are known to be strong CYP2C8 inhibitor
  2. Received enzalutamide within 60 days prior to enrollment

Phase 2b, for the combination of NUV-868 + enzalutamide only:

  1. Requires medications that are known to be strong CYP2C8 inhibitor
  2. Prior therapy with enzalutamide

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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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21224
Contact: John Torreverde    410-955-1057    jtorrev1@jhmi.edu   
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Sarah Grace    313-576-9806    graces@karmanos.org   
United States, North Carolina
Carolina BioOncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Ashley McClain    980-441-1021    AMcClain@carolinabiooncology.org   
United States, Tennessee
Sarah Cannon Research Institute - Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact       asksarah@sarahcannon.com   
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
Contact: Douglas Orr, MD    972-566-3000    referral@marycrowley.org   
Center for Oncology and Blood Disorders Recruiting
Houston, Texas, United States, 77030
Contact: Luis Camacho, MD    713-301-8964    lhcamacho@cobd.us   
Contact: Johnathan Ojo    832-540-1951    jojo@clinvax.com   
United States, Virginia
NEXT Virginia Recruiting
Fairfax, Virginia, United States, 22031
Contact: Valerie Strickland    210-580-9500    vstrickland@nextoncology.com   
Sponsors and Collaborators
Nuvation Bio Inc.
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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 4, 2022
Last Verified: September 2022

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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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Breast Neoplasms
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
Prostatic Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Gonadal Disorders
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents