NUV-868 + Olaparib/Enzalutamide for Cancer

No longer recruiting at 28 trial locations

Overseen By Nuvation Bio Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nuvation Bio Inc.

Must not be taking: CYP3A4/5 inducers, inhibitors

Disqualifiers: Pregnancy, Breastfeeding, Recent chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NUV-868 for individuals with advanced solid tumors. The goal is to determine the safety and effectiveness of NUV-868, both alone and in combination with other cancer drugs like olaparib (Lynparza) or enzalutamide (Xtandi). Suitable candidates have tumors that have worsened after previous treatments, including conditions such as prostate, ovarian, pancreatic, and triple-negative breast cancer. Participants will take the treatment daily in cycles, and the trial will explore various combinations and doses to identify the most effective approach. As a Phase 1 trial, this research aims to understand how NUV-868 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy, hormonal therapy (except certain ongoing treatments), radiation, or biological anticancer therapy at least 14 days before starting the study medication. Additionally, you cannot take medications that strongly affect certain liver enzymes (CYP3A4/5) while participating in the trial.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy, hormonal therapy (except certain ongoing treatments), radiation, or biological anticancer therapy at least 14 days before starting the study drug. Additionally, you cannot take medications that strongly affect certain liver enzymes (CYP3A4/5).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NUV-868 is designed to be more targeted, aiming to avoid the side effects seen in similar drugs. However, Nuvation Bio paused the development of NUV-868 after reviewing safety and effectiveness data, suggesting potential safety concerns during earlier testing.

When combined with olaparib, a known treatment for prostate cancer, some serious side effects have been reported, with a small number of patients experiencing fatal outcomes. This highlights potential safety risks when using olaparib in combination treatments.

Enzalutamide, another drug used with NUV-868, has safety data from previous studies. Generally, enzalutamide is well-tolerated, but it can cause side effects like tiredness and high blood pressure.

In summary, while NUV-868 shows promise in its design, its safety is still under investigation, especially in combination with other drugs. Participants should be aware that safety data is still emerging, and there are known risks with these combination therapies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NUV-868 because it offers a unique approach to cancer treatment. Unlike standard therapies that often target cancer cells broadly, NUV-868 is designed to work by targeting specific pathways within the cancer cells, potentially leading to fewer side effects and more effective results. Additionally, when combined with drugs like olaparib or enzalutamide, NUV-868 might enhance the overall treatment effectiveness by using a dual-action approach, which could be particularly beneficial for patients who do not respond well to existing treatments. This innovative strategy holds promise for improving outcomes in cancer therapy.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research shows mixed results for the effectiveness of NUV-868. In earlier studies, NUV-868 appeared promising for treating advanced solid tumors, but it did not meet all expectations, leading to a pause in its development after Phase 1 trials. In this trial, participants may receive NUV-868 alone or with other treatments. Research indicates that olaparib alone can help some cancer patients live longer, suggesting it might work well when combined with NUV-868. The combination of NUV-868 and enzalutamide also appears promising. Enzalutamide, when used with other drugs, has significantly lowered the risk of death in prostate cancer patients. However, more research is needed to confirm the effectiveness of these combinations. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors like ovarian, pancreatic, prostate, or breast cancer who have recovered from previous cancer therapy side effects and have good bone marrow and organ function. They must not be pregnant or breastfeeding, haven't had certain treatments recently, and can't have active brain disease.

Inclusion Criteria

My advanced cancer has worsened despite treatment, or there's no effective treatment for it.

My cancer is one of the specified types: ovarian, pancreatic, prostate, or breast.

My cancer can be measured or seen on tests.

Exclusion Criteria

I haven't taken experimental drugs recently.

I haven't had cancer treatment like chemo, hormone therapy, or radiation in the last 14 days.

I am currently pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Monotherapy

NUV-868 is administered at escalating dose levels until the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) is determined

28 days

Visits on Days 1, 8, and 29

Phase 1b Combination

NUV-868 is administered in combination with olaparib or enzalutamide to determine the recommended Phase 2 combination dose (RP2cD)

28 days

Visits on Days 1, 8, and 57

Phase 2 Combination

NUV-868 is administered at the RP2cD in combination with olaparib or enzalutamide to assess safety and efficacy

12 months

Every 8 weeks during the first 24 weeks, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• NUV-868
• Olaparib

Trial Overview NUV-868 is being tested alone and combined with Olaparib or Enzalutamide in patients with advanced solid tumors to find safe doses (Phase 1/1b) and test effectiveness (Phase 2). Patients take NUV-868 orally daily for 28-day cycles until they no longer benefit.

How Is the Trial Designed?

Group I: Phase 2: NUV-868 Monotherapy Experimental Treatment 1 Intervention

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

Group II: Phase 2 Combination: NUV-868 + Olaparib Experimental Treatment 2 Interventions

NUV-868 will be administered at the RP2cD. Olaparib will be administered at the RP2cD.

Group III: Phase 2 Combination: NUV-868 + Enzalutamide Experimental Treatment 2 Interventions

NUV-868 will be administered at the RP2cD. Enzalutamide will be administered at the RP2cD.

Group IV: Phase 1b Combination: NUV-868 + Olaparib Experimental Treatment 2 Interventions

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.

Group V: Phase 1b Combination: NUV-868 + Enzalutamide Experimental Treatment 2 Interventions

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.

Group VI: Phase 1 Monotherapy Experimental Treatment 1 Intervention

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.

Group VII: Phase 2: Enzalutamide Monotherapy Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Nuvation Bio Inc.

Lead Sponsor

Trials

12

Recruited

1,200+

Published Research Related to This Trial

In a phase 2 study involving 60 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide treatment led to a significant decline in prostate-specific antigen (PSA) levels in 45% of patients, indicating its efficacy in managing this advanced cancer.

The study found that the presence of the androgen receptor variant ARV7 was linked to primary resistance to enzalutamide, suggesting that certain androgen signaling characteristics before treatment can predict patient response to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Efstathiou, E., Titus, M., Wen, S., et al.[2022]

In preclinical models of metastatic castration-resistant prostate cancer, the combination of NLG207 (a HIF-1α inhibitor) and enzalutamide significantly reduced tumor volume by 93% after 3 weeks, indicating strong efficacy against enzalutamide resistance.

The addition of NLG207 enhanced the effectiveness of enzalutamide, decreasing the median tumor growth rate by 51%, suggesting that targeting both HIF-1α and androgen receptor pathways could be a promising strategy for overcoming treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models. Schmidt, KT., Chau, CH., Strope, JD., et al.[2022]

Enzalutamide significantly improves overall survival in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), with a median overall survival of 32.4 months compared to 30.2 months for placebo, based on a study of 1,717 patients.

The treatment also prolongs radiographic progression-free survival and delays the need for cytotoxic chemotherapy, while maintaining a safety profile similar to previous reports, although it requires discontinuation if seizures occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer. Ning, YM., Brave, M., Maher, VE., et al.[2021]

Enzalutamide significantly improves overall survival and radiographic progression-free survival in men with metastatic, castration-resistant prostate cancer (mCRPC), as shown in two major randomized trials (AFFIRM and PREVAIL) involving patients who had previously undergone chemotherapy and those who were chemotherapy naive.

While enzalutamide is generally safe and effective, it can cause side effects like fatigue and has specific safety concerns, such as an increased risk of seizures and falls, particularly in older patients (≥ 75 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. Graff, JN., Gordon, MJ., Beer, TM.[2021]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

In a phase 3 trial involving 256 patients with metastatic castration-resistant prostate cancer and specific genetic alterations, olaparib significantly improved overall survival compared to standard treatments (median 19.1 months vs. 14.7 months) with a hazard ratio of 0.69, indicating a 31% reduction in the risk of death.

Despite a substantial number of patients (66%) in the control group crossing over to olaparib after disease progression, the results still demonstrated that olaparib is an effective treatment option for patients with BRCA1, BRCA2, or ATM alterations, highlighting its potential as a targeted therapy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. Hussain, M., Mateo, J., Fizazi, K., et al.[2022]

In a study of 233 patients with castration-resistant prostate cancer, those starting treatment with a reduced dose of enzalutamide had a significantly lower prostate-specific antigen (PSA) response rate compared to those on the standard dose (-66.3% vs. -87.4%).

The incidence of adverse events (AEs) was not significantly different between the reduced dose and standard dose groups, suggesting that starting with a lower dose does not effectively reduce the risk of AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer. Tsuzuki, S., Nakanishi, S., Tamaki, M., et al.[2021]

In the PROFOUND phase III trial, olaparib demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) for prostate cancer patients with BRCA1/2 mutations.

These benefits were observed across various subgroups of patients, indicating olaparib's efficacy as a targeted treatment for this specific genetic profile in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial. Mateo, J., de Bono, JS., Fizazi, K., et al.[2023]

In the Phase III PROfound study, olaparib demonstrated improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to control treatments in Asian patients with metastatic castration-resistant prostate cancer, particularly in those with BRCA gene alterations.

The safety profile of olaparib in the Asian subset was consistent with the global population, showing no new safety concerns, indicating it is a well-tolerated treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Matsubara, N., Nishimura, K., Kawakami, S., et al.[2023]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05252390

Study Details | NCT05252390 | NUV-868 as Monotherapy ... NUV-868-01 is a first-in human, open- label, Phase 1/2 dose escalation and expansion study in patients with advanced solid tumors.

2. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...

3. trial.medpath.com trial.medpath.com/clinical-trial/fe50dc6bf7f3ccf2/nct05252390-safety-efficacy-study-nuv-868

NUV-868 as Monotherapy and in Combination With Olaparib ... NUV-868-01 is a first-in human, open- label, Phase 1/2 dose escalation and expansion study in patients with advanced solid tumors.

4. letswinpc.org letswinpc.org/research/targeting-cell-growth/

Targeting Pancreatic Cancer Cell Growth The trial will be studying the experimental BET inhibitor NUV-868 both on its own and in combination with two other anticancer agents. Olaparib, ...

5. trials.cancervic.org.au trials.cancervic.org.au/details/vctl_nctnct05252390

NCT05252390 - Victorian Cancer Trials Link This study is seeking to determine the safety, effectiveness and recommended dose level of a new cancer drug (called NUV-868) when it is given ...

6. clinicaltrialsarena.com clinicaltrialsarena.com/news/nuvation-bio-pauses-development-drug-safety-efficacy-analysis/

Nuvation Bio pauses oncology drug after Phase I efficacy ... Nuvation Bio has announced it will be pausing the development of its NUV-868 oncology drug following safety and efficacy analysis from a Phase I trial.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-04825

NUV-868 as Monotherapy and in Combination With ... NUV-868-01 is a first-in human, open- label, Phase 1/2 dose escalation and expansion study in patients with advanced solid tumors.

8. finance.yahoo.com finance.yahoo.com/news/small-cap-cancer-focused-nuvation-182754276.html

Small-Cap Cancer-Focused Nuvation Bio Pulls Plug On ... The company completed an internal analysis of efficacy and safety data from Phase 1 monotherapy and Phase 1b combination studies of NUV-868.

9. xtandihcp.com xtandihcp.com/crpc/safety

Safety CRPC | HCP Site | XTANDI® (enzalutamide) Learn about the efficacy and safety of XTANDI® (enzalutamide) in the results of the AFFIRM Trial for post-docetaxel mCRPC patients. See Risk Info.