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

Sponsor
Nuvation Bio Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05252390
Collaborator
(none)
246
Enrollment
1
Location
6
Arms
46.2
Anticipated Duration (Months)
5.3
Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Mar 29, 2022
Anticipated Primary Completion Date :
Jan 1, 2026
Anticipated Study Completion Date :
Feb 1, 2026

Arms and Interventions

ArmIntervention/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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Xtandi
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 1 Monotherapy Dose Escalation: Safety and tolerability of NUV-868 to determine the recommended Phase 2 dose (RP2D) [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) [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 [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 [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 [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 [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 [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 [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 [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 [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

    Eligibility Criteria

    Criteria

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

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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:

    5. 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.

    6. 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.

    7. 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.

    1. 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.

    2. 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Carolina BioOncology InstituteHuntersvilleNorth CarolinaUnited States28078

    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:
    NCT05252390
    Other Study ID Numbers:
    • NUV-868-01
    First Posted:
    Feb 23, 2022
    Last Update Posted:
    Apr 7, 2022
    Last Verified:
    Apr 1, 2022

    Study Results

    No Results Posted as of Apr 7, 2022