Trial Title:
DISCERN: Dual Versus Single ICB in PDL-1 Negative NSCLC
NCT ID:
NCT06364917
Condition:
Non Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Carboplatin
Pembrolizumab
Nivolumab
Pemetrexed
Ipilimumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
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.
Arm group label:
single agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
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.
Arm group label:
dual agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Arm group label:
single agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
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.
Arm group label:
dual agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Arm group label:
single agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
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.
Arm group label:
dual agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Arm group label:
single agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
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.
Arm group label:
dual agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Intervention type:
Drug
Intervention name:
Ipilimumab
Description:
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.
Arm group label:
dual agent immune checkpoint blockade (ICB) + chemotherapy (CT)
Summary:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the
duration of the study.
3. Male or female aged 18 years or older.
4. Participants must have histologically or cytologically confirmed non-small cell lung
cancer which is stage IV
5. 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
6. 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.
7. 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.
8. Participants should have a life expectancy of at least 3 months.
9. Participants should have a performance status of 0, 1 or 2 on the Eastern
Cooperative Oncology Group (ECOG) Performance Status
10. 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.
11. Participants should have been evaluated for circulating tumor DNA at baseline which
has been determined to be detected, present or positive.
12. 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.
13. 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.
14. 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.
15. 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:
1. Is currently participating and receiving study therapy or has participated in a
study of an investigational agent and received study therapy within 4 weeks prior to
administration of study regimen.
2. Has received a live-virus vaccination within 30 days of planned treatment start.
Seasonal flu vaccines that do not contain live virus are permitted.
3. Has clinically active diverticulitis, intra-abdominal abscess, GI obstruction,
abdominal carcinomatosis.
4. Prior treatment or history of allergy/hypersensitivity with anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CTLA-4, or other specific T-cell co-stimulation or checkpoint
targeting drugs.
5. Has a known sensitivity to any component of cisplatin, carboplatin, paclitaxel or
pemetrexed
6. Participants with carcinomatous meningitis
7. Participants with active or suspected autoimmune diseases are excluded, with the
following exceptions allowed: vitiligo, well-controlled type I diabetes mellitus,
residual hypothyroidism due to autoimmune condition requiring hormone replacement,
psoriasis not requiring systemic treatment, or conditions not expected to recur in
the absence of an external trigger.
8. Individuals who have received systemic corticosteroids or other immunosuppressive
medications within the last 14 days prior to enrollment are excluded. Exceptions are
made for topical, inhaled, nasal, ophthalmic steroids, or systemic corticosteroids
at physiological doses not to exceed 10 mg/day of prednisone or an equivalent
corticosteroid.
9. Participants with a history of ILD, or those who are suspected of having symptomatic
ILD, or those with pneumonitis.
10. Individuals with a positive test for HIV, Hep B or Hep C are excluded unless it is
well-controlled with no increased risk of immunosuppression and with no potential
drug interactions with current antiviral therapy.
11. Participants with a history of other malignancies are excluded, except for those
with basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
carcinoma in situ of the cervix, carcinoma in situ of the breast, or any cancer in
situ that has been treated curatively, and the participant has been in complete
remission for more than two years with any cancer prior to the start of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
89 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama at Birmingham
Address:
City:
Birmingham
Zip:
35294
Country:
United States
Contact:
Last name:
Margaret Thomas, MPH
Email:
margaretannthomas@uabmc.edu
Contact backup:
Last name:
Aakash Desai, MD
Contact backup:
Last name:
Maya Khalil, MD
Contact backup:
Last name:
Yanish Boumber, MD
Start date:
January 31, 2025
Completion date:
July 2027
Lead sponsor:
Agency:
University of Alabama at Birmingham
Agency class:
Other
Source:
University of Alabama at Birmingham
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06364917
