Trabedersen (OT-101) With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD-L1

Trial Title: Trabedersen (OT-101) With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD-L1

NCT ID: NCT06579196

Condition: Non-small Cell Lung Cancer

Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Pembrolizumab
Trabedersen

Conditions: Keywords:
Newly Diagnosed
PD-L1

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Intervention model description: Participants are enrolled into the Phase I arm until the recommended phase 2 dose (RP2D) is determined. Participants who receive the RP2D in Phase I are reassigned to the Phase II arm.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Trabedersen
Description: Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).
Arm group label: Arm I: Dose Finding
Arm group label: Arm II: Treatment

Other name: OT101

Intervention type: Drug
Intervention name: Pembrolizumab
Description: Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.
Arm group label: Arm I: Dose Finding
Arm group label: Arm II: Treatment

Other name: Keytruda

Summary: 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.

Detailed description: 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 participants 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. In Phase I, dose escalation/de-escalation of OT101/Trabedersen is performed using a BOIN design to determine dose limiting toxicity (DLT) and the recommended phase 2 dose (RP2D) when combined with Pembrolizumab. In Phase II, subjects receive the RP2D of OT101/Trabedersen together with Pembrolizumab until disease relapse, progression [as determined by immune Response Evaluation Criteria in Solid Tumours (iRECIST) criteria], or death.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Age ≥ 19 years. 2. A histologically/cytologically proven diagnosis of non-small cell lung cancer (NSCLC) with a PD-L1 of at least 1%. 3. Metastatic disease or disease not amenable for curative intent therapy. 4. Patients did not receive any prior treatment for metastatic NSCLC. Patients who received therapy for early-stage disease are eligible as long as it has been at least 6 months, since completion of such therapy and they did not receive immunotherapy treatment in earlier stages. 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 6. Patients must have measurable disease by RECIST criteria. 7. Adequate organ and marrow function as defined below: 1. Absolute neutrophil count ≥1,500/mm3 2. Platelets ≥100,000/mm3 3. Hemoglobin >9.0 mg/dL 4. Creatinine clearance > 60 ml/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. 5. Total serum bilirubin<1.5 X upper limit of normal (ULN) except if patient is known to have Gilbert's syndrome then they will be excluded if total bilirubin is >2.5 X ULN. 6. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN; if participant has liver metastases, ≤5x ULN. 7. Serum or urine pregnancy test (for females of childbearing potential) negative ≤7 days of treatment. 8. Male participants must agree to use effective contraception during the trial period and for 90 days after completion of treatment. 9. Female participants must not be pregnant or breast feeding. If she is at childbearing potential, she must agree to use effective contraceptive during the treatment period and 90 days after completion of treatment. 10. Able to give informed consent. Exclusion Criteria: 1. Has received any systemic treatments including investigational agents within the last 28 days. 2. Known hypersensitivity to any of the excipients of OT101 or pembrolizumab. 3. Has received radiotherapy within 14 days of the study intervention. However, palliative radiation is allowed during the study with a 1-week washout. 4. Pregnant or breast-feeding women. 5. History of autoimmune diseases that has required systemic treatment in the past 2 years with agents such as but not limited to corticosteroids or immunosuppressive drugs. However, thyroid replacement for hypothyroidism, insulin treatment for type I diabetes or corticosteroids adrenal/pituitary insufficiency are allowed. 6. Uncontrolled systemic diseases that in the opinion of the investigator may interfere with the activities described in the protocol. 7. Know active second malignancy that needs treatment. Exceptions include basal cell or squamous cancers of the skin, bladder or cervical carcinoma in situ, prostate cancer on hormone therapy alone. 8. Patient is diagnosed with immunodeficiency or receiving chronic steroids that are exceeding a dose that is equivalent to prednisone 10 mg daily. 9. Patients with symptomatic brain metastases are excluded. Patients with asymptomatic metastases or those who received treatment to the brain metastases and are off steroid therapy, can participate. 10. Known psychiatric or substance use that would interfere with the study requirements. 11. Inability to co-operate with the requirements of the protocol

Gender: All

Minimum age: 19 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University of Nebraska Medical Center

Address:
City: Omaha
Zip: 68198
Country: United States

Contact:
Last name: Omar Abughanimeh, MBBS

Phone: 402-559-7511
Email: omar.abughanimeh@unmc.edu

Investigator:
Last name: Omar Abughanimeh, MBBS
Email: Principal Investigator

Start date: January 2025

Completion date: December 2029

Lead sponsor:
Agency: University of Nebraska
Agency class: Other

Source: University of Nebraska

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06579196
https://www.oncotelic.com/wp-content/uploads/2022/07/JCA-2022.pptx.pdf
https://www.oncotelic.com/wp-content/uploads/2022/11/ASCO-SITC-2022-Final-revised2.pdf