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DISCERN: A Randomized Pilot Study Comparing Dual Versus Single Immune Checkpoint Blockade Plus Chemotherapy in PD-L1
Aakash Desai1, Ellen McNeeley1, Sanad Alhushki1
1Division of Hematology/Oncology, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL.
Background:
Immune checkpoint inhibitors (ICIs) have improved outcomes in metastatic non-small cell lung cancer (NSCLC), but benefit in tumors lacking PD-L1 expression remains limited. Dual checkpoint blockade may enhance antitumor immunity by overcoming an immunologically "cold" tumor microenvironment. Circulating tumor DNA (ctDNA) is an emerging early response biomarker.
Patients And Methods:
The DISCERN study (UAB 2432) is a single-center, randomized, open-label pilot trial comparing dual immune checkpoint blockade (nivolumab + ipilimumab) plus chemotherapy (Arm A) versus single ICI (pembrolizumab) plus chemotherapy (Arm B) in patients with PD-L1-negative, stage IV NSCLC. The study plans to enroll 24 patients. ctDNA positivity is required at baseline. ctDNA response is evaluated at Cycle 3 Day 1 using Guardant Infinity NGS platform. Primary endpoint is ctDNA molecular response. Secondary endpoints include RECIST-based response rates, progression-free survival (PFS), and overall survival (OS).
Conclusion:
DISCERN will provide novel insight into the comparative impact of dual versus single ICI regimens in PD-L1-negative NSCLC and the potential role of ctDNA clearance as an early marker of treatment efficacy in this subset of NSCLC.
Insights
Dual immune checkpoint inhibitors (ICIs) plus chemotherapy show promise for PD-L1-negative non-small cell lung cancer (NSCLC). Circulating tumor DNA (ctDNA) may serve as an early response biomarker in this patient group.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- Immune checkpoint inhibitors (ICIs) have advanced metastatic non-small cell lung cancer (NSCLC) treatment.
- Limited benefit observed in PD-L1-negative NSCLC tumors.
- Dual checkpoint blockade aims to enhance antitumor immunity in "cold" tumors.
- Circulating tumor DNA (ctDNA) is an emerging early response biomarker.
Purpose of the Study:
- To compare dual ICI plus chemotherapy versus single ICI plus chemotherapy in PD-L1-negative NSCLC.
- To evaluate ctDNA clearance as an early efficacy marker.
- To provide insights into ICI regimens for PD-L1-negative NSCLC.
Main Methods:
- The DISCERN study is a randomized, open-label pilot trial.
- Comparing nivolumab + ipilimumab + chemotherapy (Arm A) vs. pembrolizumab + chemotherapy (Arm B).
- Enrollment of 24 patients with PD-L1-negative, stage IV NSCLC and baseline ctDNA positivity.
- ctDNA response assessed using Guardant Infinity NGS platform at Cycle 3 Day 1.
- Primary endpoint: ctDNA molecular response. Secondary endpoints: RECIST response, PFS, OS.
Main Results:
- N/A
Conclusions:
- The DISCERN study will offer novel insights into dual vs. single ICI efficacy in PD-L1-negative NSCLC.
- It will explore the role of ctDNA clearance as an early treatment efficacy marker in this NSCLC subset.
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