NP-101 + Nivolumab + Ipilimumab for Cancer

Overseen By Amr Mohamed, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amr Mohamed MD

Must not be taking: Nivolumab, Ipilimumab, Antiretrovirals, others

Disqualifiers: Brain metastases, Hepatitis B/C, HIV, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new combination of treatments, including NP-101, nivolumab (Opdivo), and ipilimumab (Yervoy), to determine their effectiveness against high-grade extra-pulmonary neuroendocrine carcinoma (EP-NECA) that hasn't responded to other treatments. Derived from black seed, NP-101 is known for its antioxidant properties. Suitable candidates for this trial have advanced or metastatic EP-NECA that has recurred or isn't responding to at least one standard treatment. Participants must complete all prior chemotherapy or radiation at least three weeks before starting the study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are HIV-positive and on antiretroviral therapy, you are not eligible to participate due to potential interactions with the trial drugs.

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

Research has shown that the combination of nivolumab and ipilimumab has been tested in various cancers, such as melanoma. These studies indicate that side effects can occur, but they are usually manageable. For instance, only 2.5% of patients in one study experienced reactions during infusion, suggesting most patients handled the treatment well.

NP-101 (TQ Formula) is a new addition when used with these two drugs. Derived from black seed, it is known for its antioxidant properties. Although there is limited safety information on this specific combination, researchers are closely monitoring for any safety concerns as it is in the early stages of trials. Early trials aim to ensure treatments are safe for people, so any serious problems are usually identified quickly.

Overall, while the combination remains under study, previous evidence on nivolumab and ipilimumab suggests it might be safe for many people. However, with any new treatment, staying informed and discussing any risks with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NP-101 combined with Nivolumab and Ipilimumab because it takes a unique approach to fighting cancer. Unlike traditional treatments that primarily focus on killing cancer cells directly, this combination leverages the body’s own immune system to target and destroy cancer cells more effectively. NP-101, a TQ Formula, is believed to enhance the immune response when used alongside immune checkpoint inhibitors like Nivolumab and Ipilimumab. This novel mechanism of action could potentially lead to more durable responses and fewer side effects compared to conventional therapies.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that using nivolumab and ipilimumab together can significantly improve survival rates for various types of cancer. For example, among patients with advanced melanoma who experienced no disease progression after three years, 96% were still alive due to melanoma after ten years with this treatment combination. In non-small cell lung cancer, this drug pair led to better survival rates compared to traditional chemotherapy and reduced the risk of death by 28% in advanced kidney cancer.

In this trial, participants will receive a combination of NP-101 (TQ Formula), nivolumab, and ipilimumab. Derived from black seed, NP-101 (TQ Formula) is believed to have antioxidant properties and inhibit the growth of new blood vessels, potentially reducing blood supply to tumors. Although specific clinical data on NP-101 is limited, it is being studied for its potential to enhance the effectiveness of nivolumab and ipilimumab. ^{2 3 6 7 8}

Who Is on the Research Team?

Amr Mohamed, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced or metastatic high-grade neuroendocrine carcinomas outside the lungs who have tried at least one treatment without success. They must be in good health otherwise, with normal organ and marrow function, and no unresolved severe side effects from previous treatments. Participants need measurable disease by RECIST criteria, agree to use effective contraception methods if of childbearing potential, and sign a consent form.

Inclusion Criteria

Hemoglobin ≥ 7.0 g/dl

Examples of highly effective methods:

All previous chemotherapy or radiation must be completed at least three weeks prior to starting study treatment

Exclusion Criteria

Well-differentiated GEP-NETs are excluded from this trial

Subjects received prior nivolumab or ipilimumab

Known chronic active untreated hepatitis B or C infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NP-101 (TQ Formula) in combination with nivolumab and ipilimumab

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term safety monitoring

Participants are monitored for long-term safety and toxicity of the treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• NP-101 (TQ Formula)

Trial Overview The trial is testing a combination of NP-101 (TQ Formula), derived from black seed with antioxidant properties, along with two immunotherapy drugs: Nivolumab and Ipilimumab. This second-line therapy aims to assess its effectiveness against tumors that didn't respond to initial treatments.

How Is the Trial Designed?

Group I: NP-101 (TQ Formula) + Nivolumab + Ipilimumab Experimental Treatment 3 Interventions

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Amr Mohamed MD

Lead Sponsor

Trials

1

Recruited

20+

Novatek Pharmaceuticals

Industry Sponsor

Trials

3

Recruited

380+

Published Research Related to This Trial

After a median follow-up of nearly 55 months, the combination of nivolumab and ipilimumab significantly improved overall survival in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, with 4-year survival rates of 29% for PD-L1 ≥1% and 24% for PD-L1 <1%.

The safety profile of nivolumab plus ipilimumab remained consistent with previous studies, with immune-mediated adverse events typically occurring early in treatment and resolving quickly, indicating that discontinuation due to these events did not negatively affect long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. Paz-Ares, LG., Ramalingam, SS., Ciuleanu, TE., et al.[2022]

In a cohort of 64 adults with advanced melanoma treated with nivolumab and ipilimumab, 91% experienced clinically significant immune-related adverse events (AEs), highlighting the treatment's potential for serious side effects.

Despite the high incidence of AEs, most patients did not complete all 4 doses of the treatment, suggesting that fewer doses may still provide clinical benefits without the need for extensive immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring Toxic Effects and Time to Treatment Failure for Nivolumab Plus Ipilimumab in Melanoma. Shoushtari, AN., Friedman, CF., Navid-Azarbaijani, P., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab plus ipilimumab significantly improved overall survival in patients with metastatic non-small cell lung cancer (NSCLC), including those with baseline brain metastases, compared to chemotherapy, with a hazard ratio of 0.63 for those with brain metastases and 0.76 for those without.

At 5 years, patients with baseline brain metastases treated with nivolumab plus ipilimumab had higher rates of systemic (12%) and intracranial (16%) progression-free survival compared to chemotherapy (0% and 6%, respectively), and fewer developed new brain lesions (4% vs. 20%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1. Reck, M., Ciuleanu, TE., Lee, JS., et al.[2023]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12080919/

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in ... In patients who were progression-free at 3-years, 10-year melanoma-specific survival rates were 96% with nivolumab-plus-ipilimumab, 97% with ...

2. opdivohcp.com opdivohcp.com/efficacy/nsclc/opdivo-yervoy

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Efficacy ... Five-year survival outcomes with nivolumab plus ipilimumab versus chemotherapy as first-line treatment for metastatic non-small cell lung cancer in CheckMate ...

3. news.bms.com news.bms.com/news/details/2024/Eight-Year-Data-for-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Continue-to-Demonstrate-Longest-Survival-Benefit-vs.-Sunitinib-Reported-in-Patients-with-Previously-Untreated-Advanced-or-Metastatic-Renal-Cell-Carcinoma/default.aspx

Eight-Year Data for Opdivo (nivolumab) Plus Yervoy ... Patients with previously untreated advanced or metastatic renal cell carcinoma treated with Opdivo plus Yervoy experienced a 28% reduction in the risk of death ...

4. ctv.veeva.com ctv.veeva.com/study/np-101-tq-formula-with-nivolumab-and-ipilimumab-in-advanced-or-metastatic-extra-pulmonary-neuroend

NP-101 (TQ Formula) With Nivolumab and Ipilimumab in ... A pilot study to evaluate the anti-tumor efficacy of this novel combined regimen (NP-101 TQ Formula plus nivolumab and ipilimumab) in the ...

5. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy-combination

Advanced Melanoma Skin Cancer | Clinical Trial Results In the clinical trial, people given OPDIVO + YERVOY had a 58% lower risk of their cancer spreading, growing, or getting worse than those given YERVOY alone.

6. opdivohcp.com opdivohcp.com/safety/nsclc/opdivo-yervoy

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Safety ... In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC ...

7. nanets.net nanets.net/abstracts-archive/2022-1/1754-t10-mohamed-pilot-study-of-tq-formula-in-combination-with-nivolumab-and-ipilimumab-in-metastatic-gastroenteropancreatic-neuroendocrine-carcinomas-gep-necas/file

Pilot Study of TQ Formula in Combination with Nivolumab ... Based on our preliminary data, this pilot study is in progress to evaluate the anti-tumor efficacy of this novel combined regimen (TQ plus nivolumab and ...

8. ono-pharma.com ono-pharma.com/sites/default/files/en/news/press/sm_cn170405_3.pdf

Opdivo (nivolumab) in Combination with Yervoy ( ... The updated safety data reported in this new analysis were consistent with previously reported experience, with no cumulative toxicity noted ...