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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug OT-101/Trabedersen when combined with Pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of Non-Small Cell Lung Cancer. The main question(s) it aims to answer are: * What medical problems to participants have when taking OT101 together with Pembrolizumab? * What is the correct dose of OT-101 to use when evaluating the safety and efficacy of the combination therapy? * Does the combination therapy delay progression or relapse of the participant\'s Non-Small Cell Lung Cancer? Participants will: * Receive intravenous OT-101/Trabedersen for 4 days once every 2 weeks. Clinic visits are required to receive and disconnect the infusion. * Receive intravenous Pembrolizumab once every 6 weeks.

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.

What data supports the effectiveness of the drug pembrolizumab for lung cancer?

Pembrolizumab has been shown to improve survival in patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1, as demonstrated in clinical trials where it was compared to chemotherapy. It is approved by the FDA for certain patients with NSCLC, showing significant improvements in progression-free and overall survival. ^{1 2 3 4 5}

Is the combination of Trabedersen and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA) has been studied in various cancers, including lung cancer, and is generally considered safe, though it can cause side effects like fatigue, rash, and thyroid issues. Serious immune-related side effects, such as lung inflammation and liver problems, have also been reported. There is no specific safety data available for the combination with Trabedersen. ^{1 2 6 7 8}

What makes the drug combination of Trabedersen and Pembrolizumab unique for lung cancer treatment?

The combination of Trabedersen and Pembrolizumab is unique because it involves using Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, in combination with Trabedersen, which may enhance the immune response. This approach is novel as it combines two different mechanisms to potentially improve treatment outcomes for lung cancer. ^{1 2 4 9 10}

Research Team

Omar Abughanimeh, MBBS

Principal Investigator

University of Nebraska

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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]

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]

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]

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]

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]

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. 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]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). [2022]

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

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. United States 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. [2021]

9. France pubmed.ncbi.nlm.nih.gov

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

10. Greece pubmed.ncbi.nlm.nih.gov

Complete Response of Bone Metastasis in Non-small Cell Lung Cancer With Pembrolizumab: Two Case Reports. [2021]