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

NCT ID: NCT06579196

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-12
• Study Completion Date: 2029-02-28

Brief 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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I: 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.

Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.

Group Type: EXPERIMENTAL

Trabedersen

Intervention Type: DRUG

Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.

Arm II: Treatment

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 Type: EXPERIMENTAL

Trabedersen

Intervention Type: DRUG

Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.

Interventions

Trabedersen

Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.

Intervention Type: DRUG

Other Intervention Names

OT101; Keytruda

Eligibility Criteria

Inclusion Criteria

• Age ≥ 19 years
• Histologically/cytologically proven diagnosis of non-small cell lung cancer (NSCLC) with a PD-L1 of at least 1%
• Metastatic disease or disease not amenable for curative intent therapy
• No prior treatment for metastatic NSCLC. Early-stage disease therapy acceptable if completed at least six months prior and did not include immunotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Measurable disease by RECIST criteria
• Adequate organ and marrow function as defined below:

• Absolute neutrophil count ≥1,500/mm3
• Platelets ≥100,000/mm3
• Hemoglobin >9.0 mg/dL
• Creatinine clearance > 60 ml/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
• Total serum bilirubin <1.5 X upper limit of normal (ULN) except if known to have Gilbert's syndrome, then excluded if total bilirubin >2.5 X ULN
• 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
• For females of childbearing potential, negative serum or urine pregnancy test ≤7 days of treatment, & agree to use effective contraceptive during treatment & 90 days after end of treatment
• Male participants must agree to use effective contraception during the trial & for 90 days after end of treatment
• Able to give informed consent

Exclusion Criteria

• Received any systemic treatments including investigational agents within the last 28 days
• Known hypersensitivity to any of the excipients of OT101 or pembrolizumab
• Received radiotherapy within 14 days of the study intervention. Palliative radiation is allowed during the study with a 1-week washout
• Pregnant or breast-feeding women
• History of autoimmune diseases that required systemic treatment in the past 2 years with agents such as, but not limited to, corticosteroids or immunosuppressive drugs. Thyroid replacement for hypothyroidism, insulin treatment for type I diabetes or corticosteroids adrenal/pituitary insufficiency are allowed.
• Uncontrolled systemic diseases that in the opinion of the investigator may interfere with the protocol activities
• Known 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.
• Immunodeficiency diagnosis or receiving chronic steroids that exceed a dose equivalent to prednisone 10 mg daily
• Symptomatic brain metastases. Asymptomatic metastases or having received treatment for brain metastases and are off steroid therapy is acceptable.
• Known psychiatric or substance use that would interfere with the study requirements
• Inability to co-operate with the requirements of the protocol

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Omar Abughanimeh, MBBS

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Samuel P Anderson, BS

Role: CONTACT

samuanderson@unmc.edu

402-559-1250

Taylor A Johnson, MA

Role: CONTACT

taylora.johnson@unmc.edu

402-559-4596

Facility Contacts

Omar Abughanimeh, MBBS

Role: primary

omar.abughanimeh@unmc.edu

402-559-7511

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Related Links

https://www.oncotelic.com/wp-content/uploads/2022/07/JCA-2022.pptx.pdf

Pharmacokinetic-Pharmacodynamic (PKPD) Analysis For P001 - Phase 1/2 Clinical Trial For OT-101 Against Pancreatic Cancer, Melanoma, and Colorectal Cancer

https://www.oncotelic.com/wp-content/uploads/2022/11/ASCO-SITC-2022-Final-revised2.pdf

Mechanism of Action for OT-101 TGF-β Immunotherapy

Other Identifiers

0740-24-FB

Identifier Type: -

Identifier Source: org_study_id