NUV-1511 for Solid Tumors

Recruiting at 7 trial locations

Overseen By Nuvation Bio

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nuvation Bio Inc.

Must not be taking: Chemotherapy, Hormonal therapy

Disqualifiers: Active infection, Cardiac disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

466 Participants Needed

Trial Summary

What is the purpose of this trial?

NUV-1511-01 is a first-in human, open- label, Phase 1/2 to evaluate the safety and efficacy of NUV-1511 in patients with advanced solid tumors. The Phase 1 portion include patients with advanced solid tumors and is designed to determine the safety and the tolerability of doses of NUV-1511. In Phase 2, NUV-1511 will be given to determine the efficacy of patients with advanced solid tumors.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop chemotherapy, hormonal therapy (except certain hormone treatments), radiation therapy, or biological anticancer therapy at least 14 days before starting the study treatment. If you're on an investigational agent, you must stop it 14 to 21 days before, depending on the type of agent.

What data supports the effectiveness of the drug NUV-1511 for solid tumors?

Research shows that drugs similar to NUV-1511, which target PD-1/PD-L1 pathways, have been effective in treating various solid tumors. These drugs have been shown to improve survival rates in patients with advanced cancers, especially those with certain levels of PD-L1 expression. ^{1 2 3 4 5}

What safety data exists for NUV-1511 or similar treatments in humans?

There is no specific safety data available for NUV-1511, but a study on a similar treatment, LCL161, showed it was effective without causing systemic toxicity in mice. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with advanced solid tumors, including ovarian, prostate, pancreatic, and breast cancer. Participants should have a tumor that's progressed after treatment or has no available therapy. They must be in good physical condition with acceptable organ function.

Inclusion Criteria

Provide informed consent, which includes compliance with protocol-specified requirements and restrictions

My advanced cancer has not responded to standard treatments.

I have a specific type of cancer like HER2- breast cancer, mCRPC, pancreatic, or PROC.

Exclusion Criteria

I have recently undergone chemotherapy, hormonal, radiation, or biological therapy for cancer.

I have had a major surgery recently.

I have an autoimmune disease or a condition that weakens my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive escalating doses of NUV-1511 to determine safety and tolerability

4 weeks

Periodic visits for dose escalation and monitoring

Phase 2 Treatment

Participants receive the recommended Phase 2 dose of NUV-1511 to evaluate efficacy

Up to 5 years

Periodic efficacy assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NUV-1511

Trial Overview The study tests NUV-1511's safety and effectiveness on advanced solid tumors. It starts with Phase 1 to find the right dose based on tolerance levels. In Phase 2, the focus shifts to how well NUV-1511 works against these cancers.

Participant Groups

Group I: Phase 2: Tumor Type 2 Experimental Treatment 1 Intervention

Tumor type to be selected after Phase 1. Dose level and schedule to be selected after identification of the recommended phase 2 dose (RP2D) in Phase 1.

Group II: Phase 2: Tumor Type 1 Experimental Treatment 1 Intervention

Tumor type to be selected after Phase 1. Dose Schedules A and B to be further evaluated.

Group III: Phase 2: All comers Experimental Treatment 1 Intervention

All tumor types allowed per protocol. Dose level and schedule to be selected after identification of the recommended phase 2 dose (RP2D) in Phase 1.

Group IV: Phase 1: Schedule B Experimental Treatment 1 Intervention

Schedule B evaluating escalating dose levels of NUV-1511

Group V: Phase 1: Schedule A Experimental Treatment 1 Intervention

Schedule A evaluating escalating dose levels of NUV-1511

Who Is Running the Clinical Trial?

Nuvation Bio Inc.

Lead Sponsor

Trials

12

Recruited

1,200+

Findings from Research

In a study of 90 patients with advanced solid tumors treated with PD-1/PD-L1 inhibitors, the objective response rate was 25.6%, with a median progression-free survival of 5.5 months and median overall survival of 16.9 months, indicating promising efficacy.

Clinical factors such as ECOG performance status, smoking status, liver metastasis, and neutrophil-to-lymphocyte ratio were found to significantly influence progression-free survival, while liver metastasis and lactate dehydrogenase levels were linked to overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical observation of the efficacy of PD-1/PD-L1 inhibitors in the treatment of patients with advanced solid tumors. Wang, M., Zhen, H., Jiang, X., et al.[2021]

A systematic review of 12 randomized controlled trials involving 5410 participants showed that PD-1/PD-L1 inhibitor-chemotherapy combinations significantly improve overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) that have less than 1% PD-L1 expression.

Patients with negative PD-L1 expression (38.9% of the study population) experienced a notable benefit from these combination therapies, achieving better objective response rates compared to standard chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 inhibitors in treatment-naïve, advanced non-small cell lung cancer patients with Wankhede, D., Hofman, P., Grover, S.[2023]

In a study of 277 patients with non-small cell lung cancer (NSCLC) who underwent surgery, PD-L1 expression was found to influence tumor-specific survival (TSS), with lower survival rates in patients with higher PD-L1 levels after adjuvant therapy.

Patients with PD-L1 negative tumors had better survival outcomes following adjuvant chemotherapy compared to those with PD-L1 positive tumors, particularly in adenocarcinoma cases, suggesting that PD-L1 assessment could help tailor treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Impact of PD-L1 Expression in pN1 NSCLC: A Retrospective Single-Center Analysis. Eichhorn, F., Kriegsmann, M., Klotz, LV., et al.[2021]

In a systematic review of 24 randomized trials involving 12,966 participants, PD-1/PD-L1 inhibitors significantly improved overall survival (OS) in both PD-L1-positive (HR 0.65) and PD-L1-negative (HR 0.82) patients, indicating their efficacy across different PD-L1 statuses.

The study found a positive dose-response relationship between PD-L1 positivity and OS benefit, suggesting that higher levels of PD-L1 expression correlate with greater survival advantages from these inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of PD-L1 expression status with the efficacy of PD-1/PD-L1 inhibitors and overall survival in solid tumours: A systematic review and meta-analysis. Liu, X., Guo, CY., Tou, FF., et al.[2021]

In a systematic review of 24 trials involving over 14,860 patients, PD-1/PD-L1 inhibitors significantly reduced the risk of death compared to conventional treatments, with a hazard ratio of 0.72, indicating a strong efficacy across various tumor types.

Patients with positive PD-L1 expression (≥1%) showed improved overall survival when treated with anti-PD-1/PD-L1 monotherapy, particularly in nonsmall cell lung cancer, suggesting that PD-L1 expression can be a useful biomarker for selecting patients for this type of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Value of PD-L1 Expression in Predicting the Efficacy of Anti-PD-1 or Anti-PD-L1 Therapy in Patients with Cancer: A Systematic Review and Meta-Analysis. Chen, XJ., Yuan, SQ., Duan, JL., et al.[2022]

VX15/2503 was well tolerated in a study of 42 patients with advanced solid tumors, with most side effects being mild (grade 1 or 2), such as nausea and fatigue, indicating a favorable safety profile.

The treatment showed promising antitumor activity, with one patient achieving a partial response and 45.2% of patients maintaining stable disease for at least 8 weeks, suggesting that VX15/2503 may enhance immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. Patnaik, A., Weiss, GJ., Leonard, JE., et al.[2022]

The alpha(nu)beta(3) integrin inhibitor MK-0429 was generally well tolerated in a study of 21 men with hormone-refractory prostate cancer and bone metastases, with nausea being the most common side effect.

After 4 weeks of treatment, MK-0429 showed a significant reduction in bone turnover markers, suggesting potential clinical benefits, although there was an unexpected increase in serum prostate-specific antigen (PSA) levels, indicating disease activity may not have improved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases. Rosenthal, MA., Davidson, P., Rolland, F., et al.[2010]

ODX, a novel bone-targeting drug for castration-resistant prostate cancer, was well tolerated and showed inhibitory effects on bone metabolism markers, indicating potential efficacy in reducing metastatic burden.

In a study of 55 patients receiving different doses of ODX, significant decreases in bone alkaline phosphatase and serum-aminoterminal-propeptide of Type I procollagen were observed, suggesting that ODX may effectively target bone metastases without serious adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, dose-finding, phase II multicentre study of ODX in the treatment of patients with castration-resistant prostate cancer and skeletal metastases. Thellenberg-Karlsson, C., Vjaters, E., Kase, M., et al.[2023]

The study determined that the combination of intravenous irinotecan and oral S-1 is a tolerable treatment for advanced or recurrent cervical cancer, with a recommended dose of 80 mg/m for S-1 and 150 mg/m for irinotecan.

Out of 12 patients treated, only one experienced a dose-limiting toxicity (DLT) of febrile neutropenia at the second dose level, indicating that the regimen has an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Clinical Study of Irinotecan Plus S-1 in Patients With Advanced or Recurrent Cervical Cancer Previously Treated With Platinum-Based Chemotherapy. Mabuchi, S., Yokoi, E., Owa, T., et al.[2018]

The combination of tumor vasculature-targeted gene therapy (AAVP-TNF-α) and the IAP antagonist LCL161 significantly inhibited tumor growth and improved survival in mice with melanoma, demonstrating enhanced antitumor efficacy.

This combination therapy was more effective than using either treatment alone and did so without causing systemic toxicity, indicating a promising approach for melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of inhibitors of apoptosis (IAPs) in combination with tumor-targeted delivery of tumor necrosis factor-α leads to synergistic antitumor activity. Yuan, Z., Syrkin, G., Adem, A., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical observation of the efficacy of PD-1/PD-L1 inhibitors in the treatment of patients with advanced solid tumors. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 inhibitors in treatment-naïve, advanced non-small cell lung cancer patients with [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic Impact of PD-L1 Expression in pN1 NSCLC: A Retrospective Single-Center Analysis. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Association of PD-L1 expression status with the efficacy of PD-1/PD-L1 inhibitors and overall survival in solid tumours: A systematic review and meta-analysis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The Value of PD-L1 Expression in Predicting the Efficacy of Anti-PD-1 or Anti-PD-L1 Therapy in Patients with Cancer: A Systematic Review and Meta-Analysis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Evaluation of the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases. [2010]

8. England pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, dose-finding, phase II multicentre study of ODX in the treatment of patients with castration-resistant prostate cancer and skeletal metastases. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Phase I Clinical Study of Irinotecan Plus S-1 in Patients With Advanced or Recurrent Cervical Cancer Previously Treated With Platinum-Based Chemotherapy. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Blockade of inhibitors of apoptosis (IAPs) in combination with tumor-targeted delivery of tumor necrosis factor-α leads to synergistic antitumor activity. [2021]