Clinical trial NCT05252390: NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: 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
Keywords: 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
Lead sponsor: Nuvation Bio Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-23
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Phase 1 Monotherapy Dose Escalation: Safety and tolerability of NUV-868 to determine the recommended Phase 2 dose (RP2D)
timeFrame: During the DLT period (28 days)
measure: 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)
timeFrame: During the DLT period (28 days)
measure: Phase 1b Dose Escalation, NUV-868 + Olaparib: Pharmacokinetic (PK) profiles of NUV-868 and olaparib when administered in combination
timeFrame: Days 1, 8, and 29
measure: Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Safety and tolerability of NUV-868 in combination with enzalutamide to determine the RP2cD
timeFrame: During the DLT period (28 days)
measure: Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Pharmacokinetic (PK) profiles of NUV-868 and enzalutamide when administered in combination
timeFrame: Days 1, 8, and 57
measure: Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging
timeFrame: Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
measure: Phase 2, NUV-868 + Olaparib: Change from Baseline in PSA measurements
timeFrame: Every 4 weeks throughout study treatment, up to an average of 12 months (end of treatment)
measure: Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Naïve Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Time from First Dose to Disease Progression
timeFrame: Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
measure: Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Resistant mCRPC: Response to Study Treatment
timeFrame: 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)
measure: Phase 1b Food Effect Substudy: Effect of Food on the Pharmacokinetics (PK) of NUV-868
timeFrame: Pre dose and 24 hours after the first and second doses of NUV-868, 7 days apart
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Ellison Institute of Technology
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center - NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: North Ryde
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Hospital Newcastle
state: New South Wales
city: Malvern
country: Australia
facility: Cabrini Hospital Malvern
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
References: