Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05252390




Registration number
NCT05252390
Ethics application status
Date submitted
28/01/2022
Date registered
23/02/2022
Date last updated
29/05/2024

Titles & IDs
Public title
NUV-868 as Monotherapy and in Combination With Olaparib or Enzalutamide in Adult Patients With Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
NUV-868-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Ovarian Cancer 0 0
Ovary Cancer 0 0
Cancer of Ovary 0 0
Cancer of the Ovary 0 0
Ovary Neoplasm 0 0
Pancreatic Cancer 0 0
Pancreas Cancer 0 0
Cancer of Pancreas 0 0
Cancer of the Pancreas 0 0
Pancreas Neoplasm 0 0
Prostate Cancer 0 0
Prostatic Cancer 0 0
Cancer of Prostate 0 0
Cancer of the Prostate 0 0
Prostate Neoplasm 0 0
Castrate Resistant Prostate Cancer 0 0
Castration Resistant Prostatic Cancer 0 0
Castration Resistant Prostatic Neoplasms 0 0
Triple-negative Breast Cancer 0 0
Triple Negative Breast Cancer 0 0
Triple Negative Breast Neoplasms 0 0
Breast Cancer 0 0
Breast Carcinoma 0 0
Cancer of Breast 0 0
Cancer of the Breast 0 0
Breast Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Pancreatic
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NUV-868
Treatment: Drugs - Olaparib
Treatment: Drugs - Enzalutamide

Experimental: Phase 1 Monotherapy - 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.

Experimental: Phase 1b Combination: 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.

Experimental: Phase 1b Combination: 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.

Experimental: Phase 2 Combination: NUV-868 + Olaparib - NUV-868 will be administered at the RP2cD.
Olaparib will be administered at the RP2cD.

Experimental: Phase 2 Combination: NUV-868 + Enzalutamide - NUV-868 will be administered at the RP2cD.
Enzalutamide will be administered at the RP2cD.

Experimental: Phase 2: NUV-868 Monotherapy - NUV-868 will be administered at the RP2D in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.

Active Comparator: Phase 2: Enzalutamide Monotherapy - 160 mg enzalutamide will be administered orally daily in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.


Treatment: Drugs: NUV-868
NUV-868 is an investigational drug for oral dosing.

Treatment: Drugs: Olaparib
Olaparib

Treatment: Drugs: Enzalutamide
Enzalutamide
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1 Monotherapy Dose Escalation: Safety and tolerability of NUV-868 to determine the recommended Phase 2 dose (RP2D)
Timepoint [1] 0 0
During the DLT period (28 days)
Primary outcome [2] 0 0
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)
Timepoint [2] 0 0
During the DLT period (28 days)
Primary outcome [3] 0 0
Phase 1b Dose Escalation, NUV-868 + Olaparib: Pharmacokinetic (PK) profiles of NUV-868 and olaparib when administered in combination
Timepoint [3] 0 0
Days 1, 8, and 29
Primary outcome [4] 0 0
Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Safety and tolerability of NUV-868 in combination with enzalutamide to determine the RP2cD
Timepoint [4] 0 0
During the DLT period (28 days)
Primary outcome [5] 0 0
Phase 1b Dose Escalation, NUV-868 + Enzalutamide: Pharmacokinetic (PK) profiles of NUV-868 and enzalutamide when administered in combination
Timepoint [5] 0 0
Days 1, 8, and 57
Primary outcome [6] 0 0
Phase 2, NUV-868 + Olaparib: Change from Baseline in Tumor Imaging
Timepoint [6] 0 0
Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
Primary outcome [7] 0 0
Phase 2, NUV-868 + Olaparib: Change from Baseline in PSA measurements
Timepoint [7] 0 0
Every 4 weeks throughout study treatment, up to an average of 12 months (end of treatment)
Primary outcome [8] 0 0
Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Naïve Metastatic Castrate-Resistant Prostate Cancer (mCRPC): Time from First Dose to Disease Progression
Timepoint [8] 0 0
Every 8 weeks during the first 24 weeks and then every 12 weeks, up to an average of 12 months (end of treatment)
Primary outcome [9] 0 0
Phase 2, NUV-868 + Enzalutamide in Enzalutamide-Resistant mCRPC: Response to Study Treatment
Timepoint [9] 0 0
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 outcome [10] 0 0
Phase 1b Food Effect Substudy: Effect of Food on the Pharmacokinetics (PK) of NUV-868
Timepoint [10] 0 0
Pre dose and 24 hours after the first and second doses of NUV-868, 7 days apart

Eligibility
Key inclusion 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 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2026
Actual
Sample size
Target
657
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Macquarie University Hospital - North Ryde
Recruitment hospital [2] 0 0
Calvary Mater Hospital Newcastle - Waratah
Recruitment hospital [3] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment hospital [4] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2109 - North Ryde
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
3144 - Malvern
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Montana
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Nuvation Bio Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05252390
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nuvation Bio Inc.
Address 0 0
Country 0 0
Phone 0 0
332-208-6102
Fax 0 0
Email 0 0
clinicaltrials@nuvationbio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05252390