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

• Status: Not yet recruiting
• Trial end date: 2026-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nuvation Bio Inc.
• Treatments: Olaparib

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