82 Participants Needed

NUV-868 + Olaparib/Enzalutamide for Cancer

Recruiting at 28 trial locations
CT
EH
NB
Overseen ByNuvation Bio Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, NUV-868, taken regularly by mouth, in patients with advanced cancers. It aims to find the best dose and see if combining it with other drugs can improve treatment. The study includes patients with advanced solid tumors and a specific type of prostate cancer.

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).

What data supports the effectiveness of the drug combination NUV-868 + Olaparib/Enzalutamide for cancer?

Research shows that Olaparib, when used alone, significantly improves survival in patients with certain genetic changes and advanced prostate cancer. Enzalutamide has also been effective in treating advanced prostate cancer, and combining it with other treatments has shown promise in overcoming resistance in preclinical models.12345

What data supports the effectiveness of the drug combination NUV-868 + Olaparib/Enzalutamide for cancer?

Research shows that Olaparib, when used alone, significantly improves survival in patients with certain genetic changes in prostate cancer. Additionally, Enzalutamide has proven effective in treating advanced prostate cancer, and combining it with other drugs has shown promise in overcoming resistance in preclinical models.12345

Is the combination of NUV-868, Olaparib, and Enzalutamide safe for humans?

Enzalutamide has been studied for safety in prostate cancer patients, showing some risks like seizures, high blood pressure, and falls. Olaparib has been used in prostate cancer treatment, but specific safety details are not provided in the available research. No specific safety data for NUV-868 is mentioned in the research provided.56789

What safety information is available for Enzalutamide and Olaparib in cancer treatment?

Enzalutamide has been associated with side effects like seizures, high blood pressure, and falls, and should be stopped if a seizure occurs. Olaparib has been studied in prostate cancer, but specific safety details are not provided in the available research.56789

What makes the drug NUV-868 combined with Olaparib or Enzalutamide unique for cancer treatment?

NUV-868 combined with Olaparib or Enzalutamide is unique because it targets specific pathways in cancer cells, potentially overcoming resistance to existing treatments like enzalutamide. This combination may offer a new approach for patients with advanced prostate cancer who have not responded to other therapies.134510

What makes the drug NUV-868 combined with Olaparib or Enzalutamide unique for cancer treatment?

NUV-868 combined with Olaparib or Enzalutamide is unique because it targets specific pathways involved in cancer progression, potentially offering a new approach for patients who have developed resistance to existing treatments like enzalutamide. This combination may enhance the effectiveness of current therapies by addressing different mechanisms of cancer cell survival.134510

Eligibility Criteria

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.
See 10 more

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.
See 1 more

Timeline

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

Treatment Details

Interventions

  • Enzalutamide
  • NUV-868
  • Olaparib
Trial OverviewNUV-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.
Participant Groups
7Treatment groups
Experimental Treatment
Active Control
Group I: Phase 2: NUV-868 MonotherapyExperimental Treatment1 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 + OlaparibExperimental Treatment2 Interventions
NUV-868 will be administered at the RP2cD. Olaparib will be administered at the RP2cD.
Group III: Phase 2 Combination: NUV-868 + EnzalutamideExperimental Treatment2 Interventions
NUV-868 will be administered at the RP2cD. Enzalutamide will be administered at the RP2cD.
Group IV: Phase 1b Combination: NUV-868 + OlaparibExperimental Treatment2 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 + EnzalutamideExperimental Treatment2 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 MonotherapyExperimental Treatment1 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 MonotherapyActive Control1 Intervention
160 mg enzalutamide will be administered orally daily in one arm of a randomized Phase 2 combination (NUV-868 + enzalutamide) cohort.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Nuvation Bio Inc.

Lead Sponsor

Trials
12
Recruited
1,200+

Findings from Research

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.
Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models.Schmidt, KT., Chau, CH., Strope, JD., et al.[2022]
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.
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 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.
Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer.Efstathiou, E., Titus, M., Wen, S., et al.[2022]

References

Antitumor Activity of NLG207 (Formerly CRLX101) in Combination with Enzalutamide in Preclinical Prostate Cancer Models. [2022]
Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial. [2023]
Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. [2022]
Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. [2023]
Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. [2022]
Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer. [2021]
U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer. [2021]
Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]
Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. [2023]
Safety and effectiveness of enzalutamide in men with metastatic, castration-resistant prostate cancer. [2021]