CD47 Expression Predicts Response to Magrolimab Plus Docetaxel in Metastatic NSCLC
核心洞察
Patients with mNSCLC (搜索) treated with magrolimab plus docetaxel showed improved outcomes correlated with peripheral CD47 (搜索) saturation, according to a phase 2 trial biomarker analysis.
Higher baseline CD47 (搜索) expression on tumor cells (>50%) was associated with a significantly longer median progression-free survival (PFS) of 8.9 months compared to lower expression.
ctDNA analysis revealed that lower mean variant allele frequency (VAF) in baseline samples was prognostic for longer PFS, indicating molecular response correlates with clinical response.
Treatment with magrolimab plus docetaxel in metastatic non-small cell lung cancer (mNSCLC (搜索)) demonstrates a correlation between peripheral CD47 (搜索) saturation and improved patient outcomes, according to biomarker analysis from the phase 2 ELEVATELung&UC trial presented at the 2024 SITC Annual Meeting. The study, though ultimately terminated by Gilead, suggests that CD47 expression levels may serve as a prognostic indicator for treatment response.
CD47 Expression and Progression-Free Survival
The analysis revealed that patients with confirmed partial or complete responses to the magrolimab plus docetaxel regimen exhibited higher baseline levels of CD47 (搜索) expression. Specifically, individuals with CD47 expression on more than 50% of tumor cells experienced a median progression-free survival (PFS) of 8.9 months (95% CI, 1.1-10.2), compared to 2.6 months (95% CI, 0.8-5.4) in those with lower baseline CD47 expression (HR, 0.60; 95% CI, 0.24-1.54). The median PFS in the intention-to-treat (ITT) NSCLC (搜索) population was 5.4 months.
According to Nick van Buuren, of Gilead Sciences, lead study author, the correlation between CD47 (搜索) expression and improved outcomes suggests a positive prognostic role for CD47 in mNSCLC (搜索).
Additional Biomarker Findings
The study also explored other potential biomarkers. Magrolimab treatment triggered a plasma myeloid cytokine response without peripheral blood monocyte activation and did not induce interferon-related plasma cytokine production. Circulating tumor DNA (ctDNA) data aligned with patient responses, and baseline macrophage gene signatures did not correlate with magrolimab response. Notably, one responder showed tumor macrophage infiltration on day 1 of cycle 3.
Mean variant allele frequency (VAF) in baseline ctDNA samples was also found to be prognostic. Patients with a lower mean VAF were associated with a longer PFS. Specifically, patients with a mean VAF at or above the median of 2.8% had a median PFS of 3.0 months (95% CI, 1.9-NA), while those with a mean VAF below the median had a median PFS of 6.0 months (95% CI, 1.9-12.0). Patients with ctDNA-low disease, defined by insufficient molecular somatic variant counts, had a median PFS of 10.1 months (95% CI, 4.2-NA). Furthermore, patients who achieved a response per RECIST 1.1 criteria were more likely to achieve a molecular response at cycle 1 day 1.
Trial Design and Patient Characteristics
The ELEVATE-Lung&UC trial was a multicohort, open-label study evaluating the safety, tolerability, and efficacy of magrolimab plus docetaxel in mNSCLC (搜索), metastatic small cell lung cancer (mSCLC (搜索)), and metastatic urothelial cancer (搜索). The mNSCLC cohort (n = 31) included patients who had received 1 to 2 prior lines of platinum-based chemotherapy and/or a checkpoint inhibitor. Baseline tumor biopsies were mandatory for CD47 (搜索) immunohistochemistry (IHC) and RNA-Seq analysis.
Patients received magrolimab at a priming dose of 1 mg/kg on cycle 1 day 1, followed by a weekly dose of 30 mg/kg from cycle 1 day 8 to cycle 2 day 15, and a maintenance dose of 60 mg/kg every 3 weeks from cycle 3 day 1 onward. Docetaxel was administered at 75 mg/m2 every 3 weeks.
In the ITT population (n = 31), the median age was 65 years, with most patients being male (77.4%) and White (90.3%). The best overall responses to magrolimab plus docetaxel included CR or PR (19.4%), stable disease (SD; 38.7%), and progressive disease (PD; 16.1%).
Trial Termination
In February 2024, Gilead announced a global pause in enrollment to studies investigating magrolimab in solid tumors, including ELEVATELung&UC, to review the risk-benefit profile. The FDA subsequently requested a partial clinical hold on these trials, and Gilead later decided to terminate the ELEVATELung&UC trial.