Clinical trial NCT06579196: Trabedersen (OT-101) With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD-L1
Official title: Evaluation of Trabedersen (OT-101) With Pembrolizumab in Patients With Newly Diagnosed Advanced Non-Small Cell Lung Cancer and Positive PD-L1
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Newly Diagnosed
PD-L1
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2024-08-30
Enrollment: 45
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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

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\&#39;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.

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

Primary outcomes:
measure: Phase I: Dose Finding
timeFrame: 18 months
measure: Phase II: Progression-Free Survival (PFS)
timeFrame: 36 months
Secondary outcomes:
measure: Best Overall Response
timeFrame: 36 months
measure: Disease Control
timeFrame: 36 months
measure: Duration of Response
timeFrame: 36 months
measure: Drug Toxicity
timeFrame: 18 months
measure: Overall Survival (OS)
timeFrame: 48 months
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Omar Abughanimeh, MBBS
role: PRINCIPAL_INVESTIGATOR
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