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Updated: Jul 4, 2026
Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Clinical Outcomes of the POPCORN Study: Pharmacodynamics of Pre-Operative PD1 CheckpOint Blockade and Receptor
Elizabeth Ahern1,2,3, Cassie Turner1,4, Rishendran Naidoo5
1Department of Medical Oncology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
Background:
There is a growing body of evidence supporting neoadjuvant systemic therapy to improve outcomes for people with early-stage non-small cell lung cancer (NSCLC). However, not all patients will respond, necessitating the need to explore novel combinations and predictors of response to neoadjuvant therapies.
Patients And Methods:
In this open-label Phase 1B/2 signal-seeking trial, we recruited people with resectable Stage IB-IIIA NSCLC. Participants received two cycles of nivolumab with denosumab or nivolumab alone prior to surgical resection. Key clinical outcomes included the degree of pathological response, radiological overall response rate, recurrence-free survival, and overall survival. Tumor-immune correlates with pathological response were also investigated.
Results:
Ten participants were recruited between August 2019 and September 2021, with five participants allocated to each treatment arm using minimization for tumor stage and histopathology. Two participants (20%) achieved a pathological complete response, with a further one patient achieving a major pathological response. Density of infiltrating CD8+ T cells correlated with the degree of pathological response to neoadjuvant therapy. With a median follow-up of 38.1 months, all patients remained alive at data cutoff. The 36-month recurrence-free survival was 80%. Treatment-related adverse events were reported in three patients (30%), all of which were Grade 1-2.
Conclusion:
Our results support the feasibility of neoadjuvant systemic therapy in resectable NSCLC and explore the novel combination of nivolumab with denosumab. CD8 T-cell infiltration correlates with pathological response, warranting ongoing translational research to better understand patient selection for such novel combinations.
Insights
Neoadjuvant nivolumab with or without denosumab shows promise for early-stage non-small cell lung cancer (NSCLC). High CD8 T-cell infiltration predicts better pathological response, suggesting a biomarker for treatment selection in NSCLC.
Area of Science:
- Oncology
- Immunotherapy
- Thoracic Surgery
Background:
- Neoadjuvant systemic therapy improves outcomes in early-stage non-small cell lung cancer (NSCLC).
- Patient response to neoadjuvant therapies varies, highlighting the need for novel combinations and response predictors.
- Identifying predictors of response is crucial for optimizing neoadjuvant treatment strategies in NSCLC.
Purpose of the Study:
- To evaluate the feasibility and preliminary efficacy of neoadjuvant nivolumab combined with denosumab in resectable NSCLC.
- To explore the relationship between tumor-immune correlates and pathological response to neoadjuvant therapy.
- To assess clinical outcomes including pathological response, recurrence-free survival, and overall survival.
Main Methods:
- An open-label Phase 1B/2 signal-seeking trial involving patients with resectable Stage IB-IIIA NSCLC.
- Participants received two cycles of nivolumab with denosumab or nivolumab alone before surgical resection.
- Tumor-immune correlates, pathological response, radiological response, and survival outcomes were investigated.
Main Results:
- Two out of ten participants (20%) achieved a pathological complete response; one had a major pathological response.
- Density of infiltrating CD8+ T cells correlated with the degree of pathological response.
- With a median follow-up of 38.1 months, all patients were alive, and 36-month recurrence-free survival was 80%.
Conclusions:
- Neoadjuvant systemic therapy, including the combination of nivolumab and denosumab, is feasible in resectable NSCLC.
- CD8 T-cell infiltration is a potential biomarker for pathological response to neoadjuvant therapy.
- Further translational research is warranted to optimize patient selection for novel neoadjuvant combinations in NSCLC.
