NG-350A + Pembrolizumab for Advanced Epithelial Cancer

(FORTIFY Trial)

Recruiting at 9 trial locations

Overseen By Akamis Bio Ltd

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Akamis Bio

Must not be taking: Antivirals, Immunosuppressants, Vaccines, others

Disqualifiers: Transplantation, Active infections, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

198 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-350A in combination with pembrolizumab in patients with metastatic or advanced epithelial tumours.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like antiviral agents and some vaccines must not be taken shortly before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug NG-350A + Pembrolizumab for Advanced Epithelial Cancer?

Pembrolizumab, one of the drugs in this treatment, has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. ^{1 2 3 4 5}

Is the combination of NG-350A and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been shown to be generally safe in humans, with common side effects including fatigue, rash, itching, and diarrhea. Less common side effects can include immune-related issues like thyroid problems, inflammation of the colon, liver inflammation, and lung inflammation. While specific safety data for NG-350A is not provided, pembrolizumab has been well-tolerated in various cancer treatments. ^{1 2 6 7 8}

How is the drug NG-350A + Pembrolizumab unique for advanced epithelial cancer?

This treatment combines NG-350A, a novel component, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells by blocking the PD-1 pathway. This combination may offer a new approach for treating advanced epithelial cancer by enhancing the immune response against tumors. ^{1 2 9 10 11}

Eligibility Criteria

Adults over 18 with advanced epithelial cancer that's relapsed or doesn't respond to standard treatments, or when no standard treatment exists. Participants must have a measurable disease site, be in good physical condition (ECOG 0-1), and have proper organ function. They should not have significant infection risks, bleeding disorders, recent vaccinations, autoimmune diseases requiring recent treatment, certain drug treatments within specific time frames before the trial starts, active brain metastases, or known allergies to study drugs.

Inclusion Criteria

Predicted life expectancy of ≥6 months

I am fully active or restricted in physically strenuous activity but can do light work.

Provide written informed consent to participate

Exclusion Criteria

I have had or am planning to have a bone marrow or organ transplant.

I have used specific treatments before.

I do not have any ongoing infections needing strong medication or hospital care.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Treatment

NG-350A administered by IV infusion in combination with fixed-dose pembrolizumab in patients with metastatic or advanced tumours

8-12 weeks

Phase 1b Treatment

Further investigation of the efficacy and safety of the selected dose regimen in up to three tumour types evaluated in Phase 1a

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 weeks

Treatment Details

Interventions

• NG-350A
• Pembrolizumab

Trial Overview The FORTIFY trial is testing NG-350A combined with Pembrolizumab on patients with metastatic or advanced epithelial tumors. It's an early-phase study (phase 1a/1b) where all participants receive the experimental therapy without being randomly assigned to different groups.

Participant Groups

Group I: All cohorts Experimental Treatment 1 Intervention

NG-350A and pembrolizumab

Who Is Running the Clinical Trial?

Akamis Bio

Lead Sponsor

Trials

13

Recruited

820+

PsiOxus Therapeutics Ltd

Lead Sponsor

Trials

12

Recruited

790+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab is a monoclonal antibody that blocks the PD-1/PD-L1 interaction, which is crucial for preventing the immune system from attacking tumors, making it a key player in cancer immunotherapy.

It has been approved by the FDA for treating patients with advanced melanoma who have not responded to previous treatments, highlighting its efficacy in managing difficult cases of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. Improta, G., Leone, I., Donia, M., et al.[2020]

In a phase 2 trial involving 12 patients with advanced osteosarcoma, pembrolizumab showed no clinical benefit at 18 weeks, with all patients experiencing disease progression and a median overall survival of only 6.6 months.

Despite the lack of significant antitumor activity, pembrolizumab was well-tolerated, with no treatment-related deaths or severe adverse events, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Boye, K., Longhi, A., Guren, T., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In the phase Ib KEYNOTE-001 study, pembrolizumab monotherapy showed durable antitumor activity in advanced non-small-cell lung cancer (NSCLC), with a median overall survival (OS) of 22.3 months for treatment-naive patients and 10.5 months for previously treated patients, and 5-year OS rates of 23.2% and 15.5%, respectively.

Patients with a PD-L1 tumor proportion score of 50% or greater had even better outcomes, with 5-year OS rates of 29.6% for treatment-naive and 25.0% for previously treated patients, while the treatment maintained a favorable safety profile with minimal late-onset adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. Garon, EB., Hellmann, MD., Rizvi, NA., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

New developments in the management of advanced melanoma - role of pembrolizumab. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

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

Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. [2022]

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

10. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]