Trabedersen + Pembrolizumab for Lung Cancer

Overseen By Samuel P Anderson, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Nebraska

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Pregnancy, Autoimmune diseases, Immunodeficiency, 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: Until progression or relapse

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new drug combination, Trabedersen and Pembrolizumab (also known as KEYTRUDA), for individuals with Non-Small Cell Lung Cancer (NSCLC). Researchers aim to determine if this treatment can delay cancer progression or recurrence. Participants will receive Trabedersen for four days every two weeks and Pembrolizumab every six weeks. This trial may suit those with NSCLC who have not yet received treatment for metastatic cancer and whose cancer has a PD-L1 level of at least 1%, a protein influencing the immune response to cancer. 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 does not specify if you need to stop taking your current medications. However, you cannot have received any systemic treatments, including investigational agents, within the last 28 days before starting the trial.

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

Research has shown that combining Trabedersen (OT-101) with Pembrolizumab has been safe in past studies. In these studies, only 33% of patients experienced moderate side effects, and no deaths occurred from the treatment, suggesting general safety. Trabedersen targets a protein that helps cancer cells evade the immune system.

Pembrolizumab has undergone extensive study and maintains a consistent safety record across many trials with different cancers. This indicates that side effects are usually predictable and manageable for most patients.

In summary, previous research has demonstrated the safety of both Trabedersen and Pembrolizumab. While side effects can occur, they are typically not severe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Trabedersen combined with Pembrolizumab for lung cancer because it introduces a novel approach to treatment. Unlike traditional treatments that primarily focus on targeting cancer cells directly, Trabedersen is designed to interfere with specific genetic messaging pathways that promote tumor growth. This mechanism could potentially stop cancer cells from communicating and spreading, offering a new way to manage lung cancer. Additionally, the combination with Pembrolizumab, an established immunotherapy, may enhance the body's immune response to fight cancer more effectively. This innovative combination could provide new hope for patients with lung cancer.

What evidence suggests that this trial's treatments could be effective for Non-Small Cell Lung Cancer?

Research has shown that Pembrolizumab, one of the treatments in this trial, can help treat non-small cell lung cancer. Studies have found that patients taking Pembrolizumab have a five-year survival rate of up to 22%, surpassing that of chemotherapy alone. This indicates that Pembrolizumab can extend the lives of some individuals with this type of lung cancer. Trabedersen, another treatment under study in this trial, blocks a protein called TGF-β2, which cancer cells use to evade the immune system. By blocking this protein, Trabedersen may enable the immune system to attack the cancer more effectively. Early research suggests that combining Trabedersen with other treatments might enhance their effectiveness, but further studies are needed to confirm this. ^{1 3 6 7 8}

Who Is on the Research Team?

Omar Abughanimeh, MBBS

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for adults with a type of lung cancer called Non-Small Cell Lung Cancer (NSCLC) that tests positive for PD-L1. Participants will need to visit the clinic regularly for treatment infusions.

Inclusion Criteria

I am 19 years old or older.

My cancer has spread and cannot be cured with surgery or radiation.

Patients must have measurable disease by RECIST criteria

Exclusion Criteria

I have not taken systemic treatment for an autoimmune disease in the last 2 years, except for thyroid, diabetes, or adrenal/pituitary issues.

Uncontrolled systemic diseases that in the opinion of the investigator may interfere with the activities described in the protocol

I haven't taken any cancer treatments or experimental drugs in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Participants receive either 140, 190, or 250 mg/m2 intravenous OT-101/Trabedersen for up to 12 weeks using a 4 days on 10 days off dosing schedule. The dose level is determined according to the Bayesian optimal interval (BOIN) design with cohort size 3. Concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.

12 weeks

Clinic visits required for infusion and monitoring

Treatment

Participants receive the recommended phase II dose of intravenous OT-101/Trabedersen until progression using a 4 days on 10 days off dosing schedule. Concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.

Until progression or relapse

Clinic visits required for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Trabedersen

Trial Overview The trial is testing the safety and optimal dose of Trabedersen when used with Pembrolizumab, as well as how effective this combination is in delaying or preventing the worsening of NSCLC.

How Is the Trial Designed?

Group I: Arm II: Treatment Experimental Treatment 2 Interventions

Participants receive the recommended phase II dose of intravenous OT-101/Trabedersen (140, 190, or 250 mg/m2) until progression using a 4 days on 10 days off dosing schedule. Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.

Group II: Arm I: Dose Finding Experimental Treatment 2 Interventions

Participants receive either 140, 190, or 250 mg/m2 intravenous OT-101/Trabedersen for up to 12 weeks using a 4 days on 10 days off dosing schedule. The dose level is determined according to the Bayesian optimal interval (BOIN) design with cohort size 3. Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.

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

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

Treatment with pembrolizumab, an immunotherapy drug, led to significant improvements in both lung tumors and bone metastases in two patients with advanced non-small cell lung cancer (NSCLC) and impending fractures.

After 3 months of treatment, both patients experienced a complete response, showing remarkable bone healing and reduced lung tumor size, suggesting that pembrolizumab may be an effective systemic therapy even in cases with severe bone complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Response of Bone Metastasis in Non-small Cell Lung Cancer With Pembrolizumab: Two Case Reports. Asano, Y., Yamamoto, N., Hayashi, K., et al.[2021]

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]

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]

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 study of 97 non-small cell lung cancer patients treated with pembrolizumab, 40% experienced treatment-related adverse events (trAEs), with common ones being rash, fatigue, and hypothyroidism.

Patients who experienced trAEs had significantly better clinical outcomes, including a higher objective response rate (38.5% vs. 8.9%), longer progression-free survival (248 days vs. 60 days), and longer overall survival (493 days vs. 144.5 days), suggesting that trAEs may be indicative of a positive response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. Lisberg, A., Tucker, DA., Goldman, JW., et al.[2022]

In a real-life study of 108 patients with advanced non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score of ≥50%, pembrolizumab showed a median progression-free survival of 10.1 months, similar to results from the KEYNOTE-024 trial.

The treatment was generally well-tolerated, with only 8% of patients experiencing grade 3 adverse events, and no severe (grade 4 or 5) adverse events reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. Amrane, K., Geier, M., Corre, R., et al.[2021]

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 (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Adjuvant platinum-based chemotherapy is the standard treatment for patients with resected non-small-cell lung cancer (NSCLC) stage IB to IIIA, but many still face disease recurrence, highlighting the need for more effective therapies.

The ALCHEMIST trial is investigating the efficacy of pembrolizumab, a PD-1 inhibitor, in combination with chemotherapy to potentially improve outcomes compared to standard chemotherapy alone, with the aim of reducing recurrence rates in NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). Sands, JM., Mandrekar, SJ., Kozono, D., 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]

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