NEO-201 + Pembrolizumab for Non-Small Cell Lung Cancer

Recruiting at 1 trial location

Overseen By Erica Redmond, BSN,RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Precision Biologics, Inc

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Uncontrolled brain metastases, Active infection, Uncontrolled diabetes, Congestive heart failure, others

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

Compensation: Varies

Number of Visits: 14

121 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with certain types of cancer, including non-small cell lung cancer, that have not responded well to initial treatments. The trial combines NEO-201 (an experimental treatment) with pembrolizumab (an immunotherapy drug) to determine if this duo can better fight cancer. Suitable candidates have advanced cancer that has worsened after first-line treatments like chemotherapy and have cancers expressing certain markers. Participants will receive these treatments regularly, with close monitoring for any side effects or improvements.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific waiting periods after certain treatments, like 14 days after oral tyrosine kinase inhibitors and 21 days after monoclonal antibodies, before you can join the trial.

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

Research shows that the combination of NEO-201 and pembrolizumab has been tested for safety in adults who did not respond to other treatments. In earlier studies, most patients tolerated this combination well, with side effects generally mild and manageable.

Pembrolizumab is already approved for treating other types of cancer, so its safety profile is well understood. NEO-201 is being tested in humans for the first time, and the safe dose has been set at 1.5 mg per kilogram of body weight, indicating it is safe enough to continue testing at this dose.

So far, no serious safety concerns have emerged for this combination. However, like all clinical trials, there is a chance of side effects. Researchers closely monitor participants to manage any possible risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of NEO-201 and pembrolizumab for non-small cell lung cancer because it offers a novel approach to treatment by potentially enhancing the immune system's ability to fight cancer. Unlike standard treatments like chemotherapy, which attack cancer cells directly, NEO-201 is an antibody that targets specific proteins on tumor cells, making it a more precise therapy. When combined with pembrolizumab, an immune checkpoint inhibitor, it may further boost the immune response against cancer cells, providing a dual-action strategy that could improve treatment outcomes.

What evidence suggests that NEO-201 in combination with pembrolizumab could be effective for non-small cell lung cancer?

Research has shown that using NEO-201 with pembrolizumab may help treat cancers like non-small cell lung cancer (NSCLC). NEO-201 targets certain cancer cells, potentially enhancing the immune system's ability to attack the cancer. In this trial, participants will receive NEO-201 combined with pembrolizumab. Earlier studies combining these treatments have shown positive results. Pembrolizumab alone has already been effective for some NSCLC patients, particularly those with high levels of a protein called PD-L1. These findings suggest that using these treatments together could offer new hope for patients who haven't responded to other therapies. ^{1 3 6 7 8}

Who Is on the Research Team?

Kevin Conlon, MD

Principal Investigator

National Cancer Institute - Women's Malignancy Branch

Charalampos Floudas, MD

Principal Investigator

National Cancer Institute - Head and Neck/GUMB

Azam Ghafoor, MD

Principal Investigator

National Cancer Institute - Thoracic and GI Malignancy Branch

Are You a Good Fit for This Trial?

Adults with certain advanced cancers (lung, head and neck, cervical, uterine) that worsened after standard treatment can join. They need a biopsy sample available or agree to a new biopsy. Participants must be at least 18 years old, not pregnant or breastfeeding, use birth control if applicable, have no severe illnesses or brain metastases under control without seizures.

Inclusion Criteria

Surgery or radiation cannot cure my condition.

I am post-menopausal, surgically sterilized, or will use birth control during and after the study.

Subject is expected to be able to remain on a study protocol for at least 8 weeks

Exclusion Criteria

Receiving any other investigational agents

You have a condition where your immune system attacks your own body, and you needed strong medication for it in the last 2 years.

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A safety lead-in will be conducted in the first 3 to 6 subjects to evaluate toxicity prior to expanding accrual. The safety lead-in will be 42 days in length, consisting of 1 dose of pembrolizumab and 3 doses of NEO-201 followed by a 2-week assessment for safety.

6 weeks

Multiple visits for dosing and safety assessment

Expansion Phase

Subjects with NSCLC, HNSCC, cervical and uterine cancers will be treated with NEO-201 at the RP2D (1.5 mg/kg) every 2 weeks in combination with pembrolizumab, given 1 day after the NEO-201, at 400 mg IV every 6 weeks.

Ongoing until disease progression or unacceptable toxicity

Every 2 weeks for NEO-201, every 6 weeks for pembrolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

1.5 years

Re-evaluation every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NEO-201
• Pembrolizumab

Trial Overview The trial is testing NEO-201 combined with pembrolizumab in patients whose cancer has progressed despite previous treatments. The study will administer NEO-201 every two weeks and pembrolizumab every six weeks to see how well they work together against the cancer.

How Is the Trial Designed?

Group I: NEO-201 in combination with pembrolizumab Experimental Treatment 1 Intervention

Subjects will receive 3 doses NEO-201 in combination with one dose of pembrolizumab in a 42 day cycle. This course will be repeated in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Precision Biologics, Inc

Lead Sponsor

Trials

4

Recruited

400+

Published Research Related to This Trial

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., 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]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

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]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab monotherapy significantly improved quality-adjusted survival (Q-TWiST) by 2.49 months compared to platinum-based chemotherapy and by 2.29 months compared to docetaxel in patients with advanced non-small cell lung cancer, indicating its efficacy in enhancing patient quality of life.

The benefits of pembrolizumab continued to increase over time, suggesting that it not only offers longer overall survival but also fewer treatment-related adverse events compared to traditional chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. Huang, M., Pietanza, MC., Samkari, A., et al.[2020]

In a study of 411 patients with non-small cell lung cancer (NSCLC), 33% showed no PD-L1 expression, 38% had low expression, and 29% exhibited high expression, indicating a significant variability in PD-L1 status among patients.

The study found that PD-L1 positivity was linked to factors such as male sex, smoking history, higher tumor grade, and specific histologic types, suggesting that these characteristics may influence the effectiveness of pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience. Takeda, M., Kasai, T., Naito, M., et al.[2022]

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]

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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Citations

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The 5‐year outcomes of the KEYNOTE‐024 trial Pembrolizumab monotherapy could provide meaningful improved patient outcomes over platinum‐based chemotherapy for advanced NSCLC patients with PD‐L1 TPS ≥ 50%.

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USPTO Grants Patent for Precision Biologics' Lead ... NEO-201 is a humanized IgG1 monoclonal antibody exhibiting multiple action mechanisms. It effectively targets cancer cells expressing truncated ...

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637 Phase IIa combining NEO-201 with pembrolizumab in ... NEO-201 reacts against colon, pancreatic, non-small cell lung, head and neck, cervical, uterine and breast cancer, but it does not bind to ...

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First-in-human phase 1 clinical trial of anti-core 1 O- ... Here, we present outcomes from a phase I trial of NEO-201 in patients with advanced solid tumors that have not responded to standard treatments.