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

Phase 1

Terminated

• Conditions: Cancer of Ovary; Prostatic Cancer; Castration Resistant Prostatic Neoplasms; Breast Tumor; Cancer of the Ovary; Prostate Cancer; Cancer of the Prostate; Triple-negative Breast Cancer; Cancer of Breast; Ovary Cancer
• Interventions: Drug: NUV-868; Drug: Enzalutamide; Drug: Olaparib

• Registration Number: NCT05252390
• Lead Sponsor: 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(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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-28
• Study First Submitted QC: 2022-02-11
• Study First Posted: 2022-02-23
• Study Start: 2022-03-29
• Primary Completion: 2024-07-15
• Study Completion: 2024-07-15
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 82

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2 Combination: NUV-868 + Olaparib	NUV-868	NUV-868 will be administered at the RP2cD. Olaparib will be administered at the RP2cD.
Phase 2 Combination: NUV-868 + Olaparib	Olaparib	NUV-868 will be administered at the RP2cD. Olaparib will be administered at the RP2cD.
Phase 2: Enzalutamide Monotherapy	Enzalutamide	160 mg enzalutamide will be administered orally daily in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.
Phase 1b Combination: NUV-868 + Enzalutamide	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.
Phase 1b Combination: NUV-868 + Olaparib	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.
Phase 2 Combination: NUV-868 + Enzalutamide	Enzalutamide	NUV-868 will be administered at the RP2cD. Enzalutamide will be administered at the RP2cD.
Phase 1b Combination: NUV-868 + Enzalutamide	NUV-868	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.
Phase 1b Combination: NUV-868 + Olaparib	NUV-868	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.
Phase 1 Monotherapy	NUV-868	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.
Phase 2 Combination: NUV-868 + Enzalutamide	NUV-868	NUV-868 will be administered at the RP2cD. Enzalutamide will be administered at the RP2cD.
Phase 2: NUV-868 Monotherapy	NUV-868	NUV-868 will be administered at the RP2D in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.

Primary Outcome Measures

Name	Time	Method
Phase 2, 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)	PSA50 response rate per standard criteria; only for patients with prostate cancer
Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging	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
Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Naïve Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Time from First Dose to Disease Progression	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
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
Phase 1b Dose Escalation, NUV-868 + Olaparib: Pharmacokinetic (PK) profiles of NUV-868 and olaparib when administered in combination	Days 1, 8, and 29	NUV-868 and olaparib combination PK
Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Resistant mCRPC: Response to Study Treatment	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
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)
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
Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Pharmacokinetic (PK) profiles of NUV-868 and enzalutamide when administered in combination	Days 1, 8, and 57	NUV-868 and enzalutamide combination PK
Phase 1b Food Effect Substudy: Effect of Food on the Pharmacokinetics (PK) of NUV-868	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

Trial Locations

Locations (21)

The University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Ellison Institute of Technology; 🇺🇸 Los Angeles, California, United States

Rocky Mountain Cancer Centers, LLP; 🇺🇸 Lone Tree, Colorado, United States

H. Lee Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, 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

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute - Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States

Texas Oncology - Fort Worth Cancer Center; 🇺🇸 Fort Worth, Texas, United States

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States

Virginia Oncology Associates; 🇺🇸 Norfolk, Virginia, United States

Macquarie University Hospital; 🇦🇺 North Ryde, New South Wales, Australia

Calvary Mater Hospital Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Cabrini Hospital Malvern; 🇦🇺 Malvern, Victoria, Australia

Peter Maccallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia