Non-small Cell Lung Cancer
Conditions
Keywords
Newly Diagnosed, PD-L1
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.
Interventions
DRUGTrabedersen
Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).
DRUGPembrolizumab
Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.
Sponsors
University of Nebraska
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Dose Finding | 18 months | Dose Limiting toxicity (DLT) and Maximum Tolerated Dose (MTD) |
| Phase II: Progression-Free Survival (PFS) | 36 months | Progression-Free Survival (PFS) defined as first therapy until the first documentation of clinical progression, relapse, or death due to any cause. Participants not experiencing an event of interest will be right-censored at last known disease status |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 36 months | Duration of response (DOR) defined as first response (CR or PR) until disease progression. |
| Best Overall Response | 36 months | Best overall response, defined as the best overall response observed during the evaluation period (up to 12 weeks of treatment): CR, PR, SD, or PD, |
| Overall Survival (OS) | 48 months | Overall survival (OS) defined as the time from the first therapy until death. |
| Drug Toxicity | 18 months | Toxicity according to Common Terminology Criteria for Adverse Events (CTCAE). |
| Disease Control | 36 months | Disease control \[CR + PR + stable disease (SD)\] |
Countries
United States
Contacts
Primary ContactSamuel P Anderson, BS
Backup ContactTaylor A Johnson, MA
Outcome results
None listed