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

15 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination NP-101, Nivolumab, and Ipilimumab for cancer?

Research shows that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) is effective in treating advanced non-small cell lung cancer (NSCLC) and melanoma, leading to longer survival compared to chemotherapy. This suggests potential effectiveness when combined with NP-101 for cancer treatment. ^{1 2 3 4 5}

What makes the NP-101 + Nivolumab + Ipilimumab drug unique for cancer treatment?

This drug combination is unique because it includes NP-101 (TQ Formula) alongside nivolumab and ipilimumab, which are known for their effectiveness in treating advanced cancers like non-small cell lung cancer (NSCLC) and melanoma. Nivolumab and ipilimumab work by boosting the immune system to fight cancer, and the addition of NP-101 may offer a novel approach to enhance this effect, although specific details about NP-101's role are not provided in the research. ^{1 5 6 7 8}

What is the purpose of this trial?

This trial tests a black seed oil formula combined with two cancer drugs in patients with neuroendocrine carcinoma who did not respond to standard treatments. The formula may enhance the immune system's ability to fight cancer and inhibit tumor growth. Thymoquinone (TQ), the major active ingredient of black seed oil, has been extensively studied for its anti-cancer properties, including promoting apoptosis, arresting the cell cycle, and generating reactive oxygen species.

Research Team

Amr Mohamed, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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, 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]

References

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

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

2. United States 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. [2022]

3. United States 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. [2023]

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

Measuring Toxic Effects and Time to Treatment Failure for Nivolumab Plus Ipilimumab in Melanoma. [2023]

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

Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study). [2023]

6. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

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