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

Locations

Arms

46.2

Anticipated Duration (Months)

49.2

Patients Per Site

1.1

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: NUV-868 Drug: Olaparib Drug: Enzalutamide	Phase 1/Phase 2

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

Arm	Intervention/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

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 + 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 [Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 2 Day 1 (each cycle is 28 days)]
NUV-868 and olaparib combination PK
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 [Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 3 Day 1 (each cycle is 28 days)]
NUV-868 and enzalutamide combination PK
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
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
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
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
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:

Inclusion Criteria For All Phases and Cohorts:

Recovered from toxicity to prior anti-cancer therapy
Adequate bone marrow and organ function
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)

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
Life expectancy of > 3 months
Eastern Cooperative Oncology Group Performance Status ≤ 2
Measurable or non-measurable disease

Phase 1b (Combination Study with Enzalutamide or Olaparib)

Life expectancy of > 3 months
Eastern Cooperative Oncology Group Performance Status ≤ 2
Measurable or non-measurable disease
One of the following tumor types:
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.
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.
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.
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.
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)

Life expectancy of > 6 months
Phase 2b (Select Cohorts Only): At least one measurable lesion defined by standard criteria
Eastern Cooperative Oncology Group Performance Status ≤ 1
One of the following tumor types:
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.
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.
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.

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.
For all tumor types: Patients will be allowed in the study regardless of their BRCA/HRR status.

Exclusion Criteria For All Phases and Cohorts:

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
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
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
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

Requires medications that are known to be strong CYP2C8 inhibitor
Received enzalutamide within 60 days prior to enrollment

Phase 2b, for the combination of NUV-868 + enzalutamide only:

Requires medications that are known to be strong CYP2C8 inhibitor
Prior therapy with enzalutamide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21224
2	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
3	Carolina BioOncology Institute	Huntersville	North Carolina	United States	28078
4	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
5	NEXT Virginia	Fairfax	Virginia	United States	22031