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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05252390
• Other study ID #: NUV-868-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 29, 2022
• Est. completion date: November 2026

Study information

• Verified date: February 2024
• Source: Nuvation Bio Inc.
• Contact: Nuvation Bio Inc.
• Phone: 332-208-6102
• Email: clinicaltrials[@]nuvationbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 657
• Est. completion date: November 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Cancer
• Breast Carcinoma
• Breast Neoplasms
• Breast Tumor
• Cancer of Breast
• Cancer of Ovary
• Cancer of Pancreas
• Cancer of Prostate
• Cancer of the Breast
• Cancer of the Ovary
• Cancer of the Pancreas
• Cancer of the Prostate
• Castrate Resistant Prostate Cancer
• Castration Resistant Prostatic Cancer
• Castration Resistant Prostatic Neoplasms
• Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Ovary Cancer
• Ovary Neoplasm
• Pancreas Cancer
• Pancreas Neoplasm
• Pancreatic Cancer
• Pancreatic Neoplasms
• Prostate Cancer
• Prostate Neoplasm
• Prostatic Cancer
• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Triple-negative Breast Cancer

Intervention

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

Locations

Country	Name	City	State
Australia	Cabrini Hospital Malvern	Malvern	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	Macquarie University Hospital	North Ryde	New South Wales
Australia	Calvary Mater Hospital Newcastle	Waratah	New South Wales
United States	Rocky Mountain Cancer Centers, LLP	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Vincent-Frontier Cancer Center	Billings	Montana
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain, Cancer Centers, LLP	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	NEXT Virginia	Fairfax	Virginia
United States	Texas Oncology - Fort Worth Cancer Center	Fort Worth	Texas
United States	Center for Oncology and Blood Disorders	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Rocky Mountain Cancer Centers, LLP	Lone Tree	Colorado
United States	Lawrence J. Ellison Institute for Transformative Medicine	Los Angeles	California
United States	Morristown Medical Center	Morristown	New Jersey
United States	Sarah Cannon Research Institute - Tennessee Oncology	Nashville	Tennessee
United States	Laura & Isaac Perlmutter Cancer Center - NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Abramson Cancer Center of the U of Penn.	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Atlantic Health System / Overlook Medical Center	Summit	New Jersey
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Tampa General Hospital Cancer Center of South Florida	Tampa	Florida
United States	The University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Nuvation Bio Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Monotherapy Dose Escalation: Safety and tolerability of NUV-868 to determine the recommended Phase 2 dose (RP2D)	Incidence of dose-limiting toxicities (DLTs)	During the DLT period (28 days)
Primary	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)	Incidence of DLTs	During the DLT period (28 days)
Primary	Phase 1b Dose Escalation, NUV-868 + Olaparib: Pharmacokinetic (PK) profiles of NUV-868 and olaparib when administered in combination	NUV-868 and olaparib combination PK	Days 1, 8, and 29
Primary	Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Safety and tolerability of NUV-868 in combination with enzalutamide to determine the RP2cD	Incidence of DLTs	During the DLT period (28 days)
Primary	Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Pharmacokinetic (PK) profiles of NUV-868 and enzalutamide when administered in combination	NUV-868 and enzalutamide combination PK	Days 1, 8, and 57
Primary	Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging	ORR per standard criteria	Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
Primary	Phase 2, NUV-868 + Olaparib: Change from Baseline in PSA measurements	PSA50 response rate per standard criteria; only for patients with prostate cancer	Every 4 weeks throughout study treatment, up to an average of 12 months (end of treatment)
Primary	Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Naïve Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Time from First Dose to Disease Progression	Radiographic progression-free survival (rPFS) per standard criteria	Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
Primary	Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Resistant mCRPC: Response to Study Treatment	Composite response rate (CRR: radiologic response, PSA50 response, and/or circulating tumor cell response) per standard criteria	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)
Primary	Phase 1b Food Effect Substudy: Effect of Food on the Pharmacokinetics (PK) of NUV-868	NUV-868 PK parameters in fed and fasted states	Pre dose and 24 hours after the first and second doses of NUV-868, 7 days apart