Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| Robert Award | Other Identifier | The University of Alabama at Birmingham |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study, known as DISCERN, is to compare two different treatments for a type of lung cancer called non-small cell lung cancer (NSCLC) that does not show a marker known as PD-L1. This study will help us understand if using two types of immune therapy together with chemotherapy is better than using one type of immune therapy with chemotherapy. We're doing this by looking at changes in the subject's cancer's DNA in the blood after starting treatment.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| single agent immune checkpoint blockade (ICB) + chemotherapy (CT) | Experimental | 200 mg of Pembrolizumab will be administered intravenously (IV) every 3 weeks (Q3W) for 4 cycles. Combination chemotherapy: For squamous NSCLC: Carboplatin (dose according to area under the curve (AUC) 6) + paclitaxel 200 mg/m². For non-squamous NSCLC: Carboplatin (AUC 5) + pemetrexed 500 mg/m². Maintenance Therapy for Non-Squamous NSCLC: Pembrolizumab 200 mg + pemetrexed 500 mg/m² Q3W for up to 2 years. |
|
| dual agent immune checkpoint blockade (ICB) + chemotherapy (CT) | Experimental | Drug 1: 360 mg of Nivolumab will be administered intravenously (IV) every 3 weeks (Q3W). Drug 2: 1 mg/kg of Ipilimumab will be administered intravenously (IV) every 6 weeks (Q6W) for 2 cycles. Combination Chemotherapy: For squamous NSCLC: Carboplatin (AUC 6) + paclitaxel 200 mg/m². For non-squamous NSCLC: Carboplatin (AUC 5) + pemetrexed 500 mg/m². Maintenance Therapy for Non-Squamous NSCLC: Nivolumab 360 mg Q3W + Ipilimumab 1mg/kg Q6W for up to 2 years. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Drug | The dosing regimens for Pembrolizumab (200 mg Q3W), are based on established FDA-approved dosages for the treatment of NSCLC, ensuring a balance between efficacy and tolerability. These doses are selected based on extensive clinical experience indicating optimal response rates with manageable safety profiles in the target population. The route of administration (intravenous) is chosen for its direct delivery into the bloodstream, ensuring maximum bioavailability and consistency of dosing. |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Molecular Response in Patients with PD-L1 Negative Advanced NSCLC Treated with Dual vs. Single ICB Plus CT Regimens | To assess and quantify the rate of molecular response, defined as the complete disappearance of circulating tumor DNA (ctDNA) from baseline levels, by Cycle 4 Day 1 (C4D1). This study compares patients with PD-L1 negative advanced non-small cell lung cancer (NSCLC) who are treated with a dual immune checkpoint blockade (ICB) plus chemotherapy (CT) strategy against those receiving a single ICB plus CT regimen. The objective explores whether the addition of a second ICB enhances the molecular response when integrated into standard chemoimmunotherapy protocols in this specific patient population. | Baseline to 64 days (C4D1) |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy Evaluation | To determine the Overall Response Rate (ORR) in patients receiving dual immune checkpoint blockade (ICB) plus chemotherapy (CT) and those receiving single ICB plus CT. The ORR will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Baseline up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | To evaluate the median Progression-Free Survival (PFS) among patients treated with dual immune checkpoint blockade (ICB) plus chemotherapy (CT) compared to those receiving single ICB plus CT. The aim is to evaluate the impact of the combined treatment strategy on disease progression. | Baseline to 24 months |
Inclusion Criteria:
Provision of signed and dated informed consent form.
Stated willingness to comply with all study procedures and availability for the duration of the study.
Male or female aged 18 years or older.
Participants must have histologically or cytologically confirmed non-small cell lung cancer which is stage IV
Participants should not have a known sensitizing mutation for which an FDA-approved.
targeted therapy for NSCLC exists in first line (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, and MET sensitizing mutations
Participants should not have received prior systemic anticancer therapy for advanced or metastatic disease. For patients who are recently diagnosed and received one cycle of chemotherapy while awaiting NGS/PDL-1 testing are allowed on study after discussion with medical monitor.
Participants should have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Participants should have a life expectancy of at least 3 months.
Participants should have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
Participants should have provided tumor tissue from locations not radiated prior to biopsy; fresh formalin fixed specimens or archival samples which have been determined as PD-L1 status <1% or negative prior to randomization.
Participants should have been evaluated for circulating tumor DNA at baseline which has been determined to be detected, present or positive.
Participants with CNS metastases are eligible if all metastases have been treated and have remained stable without growth for at least 2 weeks post-treatment, the participant's neurological status has returned to baseline or remained stable for at least 2 weeks, and any use of corticosteroids for CNS metastases is at a dose of ≤10 mg daily prednisone (or an equivalent dose of another corticosteroid) and has been stable for at least 2 weeks before enrollment.
Participants should have adequate organ function to be able to safely receive the approved standard of care regimens per the current FDA approved package insert, treating investigators discretion and institutional guidelines.
For females of reproductive potential: Negative urine and serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, serum pregnancy test will be required. Participants should be willing to use an adequate method of contraception for the course of the study through 120 days after last dose of study medication or through 180 days after last dose of chemotherapeutic agents. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Aakash Desai, MD, MPH | Contact | (205) 934-3411 | aakashdesai@uabmc.edu | |
| Margaret Thomas, MPH | Contact | margaretannthomas@uabmc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Aakash Desai, MD | University of Alabama at Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Recruiting | Birmingham | Alabama | 35294 | United States |
Not provided
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| D000068437 | Pemetrexed |
| D000077594 | Nivolumab |
| D000074324 | Ipilimumab |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Carboplatin | Drug | The combination therapy dosages for Carboplatin are aligned with standard chemotherapy protocols for NSCLC, tailored to minimize toxicity while maintaining therapeutic efficacy. This dosing strategy is justified by previous phase 3 trials demonstrating the effectiveness and safety of these regimens in advanced NSCLC patients. |
|
| Paclitaxel | Drug | The combination therapy dosages for Paclitaxel are aligned with standard chemotherapy protocols for NSCLC, tailored to minimize toxicity while maintaining therapeutic efficacy. This dosing strategy is justified by previous phase 3 trials demonstrating the effectiveness and safety of these regimens in advanced NSCLC patients. |
|
| Pemetrexed | Drug | The combination therapy dosages for Pemetrexed are aligned with standard chemotherapy protocols for NSCLC, tailored to minimize toxicity while maintaining therapeutic efficacy. This dosing strategy is justified by previous phase 3 trials demonstrating the effectiveness and safety of these regimens in advanced NSCLC patients. |
|
| Nivolumab | Drug | The dosing regimens for Nivolumab (360 mg Q3W) are based on established FDA-approved dosages for the treatment of NSCLC, ensuring a balance between efficacy and tolerability. These doses are selected based on extensive clinical experience indicating optimal response rates with manageable safety profiles in the target population. The route of administration (intravenous) is chosen for its direct delivery into the bloodstream, ensuring maximum bioavailability and consistency of dosing. |
|
| Ipilimumab | Drug | The dosing regimens for Ipilimumab (1 mg/kg Q6W) are based on established FDA-approved dosages for the treatment of NSCLC, ensuring a balance between efficacy and tolerability. These doses are selected based on extensive clinical experience indicating optimal response rates with manageable safety profiles in the target population. The route of administration (intravenous) is chosen for its direct delivery into the bloodstream, ensuring maximum bioavailability and consistency of dosing. |
|
| Correlation Analysis |
To investigate the correlation between ctDNA responses at Cycle 4 Day 1 (C4D1) and traditional RECIST v1.1 criteria in patients receiving dual versus single ICB plus CT. The analysis aims to validate ctDNA as a predictive biomarker for treatment response. |
| Baseline up to 24 months |
| Median Overall Survival (OS) |
To evaluates the median Overall Survival (OS) in patients receiving dual ICB plus CT versus those treated with single ICB plus CT, offering insights into the long-term benefits of these treatment regimens. |
| Baseline to 24 months |
| Tolerability Assessment | To assess the tolerability of dual versus single ICB plus CT strategies using patient-reported outcomes (PROs). The focus is on evaluating the patient experience and side effect profiles associated with these treatment options in patients with PD-L1 negative advanced NSCLC. | Baseline to 24 months |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D003516 |
| Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |