Magrolimab-Chemo Combo Improves Responses in Metastatic NSCLC

Improved outcomes were seen with magrolimab plus docetaxel in patients with metastatic non-small cell lung cancer (NSCLC) who had higher CD47 expressions, according to a presentation on the phase 2 ELEVATELung&UC trial at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting.

Magrolimab is a type of monoclonal antibody that targets CD47 by binding to it, according to the National Cancer Institute. When the drug binds to CD47, it helps destroy the cancer cells directly. In the study, magrolimab was combined with docetaxel, a type of chemotherapy. 

The study included 31 patients with metastatic NSCLC who previously received treatment in the second- or later-line setting. Researchers found that patients with NSCLC with confirmed partial responses (PRs) or complete responses (CRs) to magrolimab plus docetaxel had higher baseline levels of CD47 expression.

Among patients with CD47 expression on more than 50% of tumor cells, the median progression-free survival (PFS) was 8.9 months versus 2.6 months for those with baseline CD47 expression below 50%. The median PFS in the NSCLC population treated with magrolimab plus docetaxel was 5.4 months.

“Despite a limited sample size, the correlation between CD47 expression and better outcome in both [ELEVATELung&UC] and in Tempus real-world data of patients treated with chemotherapy and/or [immunotherapy] suggests a positive prognostic role for CD47 in metastatic NSCLC,” lead study author Nick van Buuren, of Gilead Sciences and coauthors, wrote in a poster of the data.

More About the ELEVATE-Lung&UC Trial

Among the 31 patients with metastatic NSCLC in the study who received treatment (intent-to-treat population; ITT), the median age was 65 years. Most patients were male (77.4%), White (90.3%), had stage 4 disease (96.8%), had an ECOG performance score of 1 at baseline (54.8%) and were former smokers (58.1%). The best overall responses to magrolimab plus docetaxel in this population included CR or PR (19.4%), stable disease (SD; 38.7%) and progressive disease (PD; 16.1%).

The biomarker-evaluable population was a subset of 24 patients with stage 4 NSCLC who had reportable baseline CD47 results. The patient characteristics and best overall response rates reflected those observed in the ITT population. In this population, the median age was 64 years. Most patients were male (75%), White (87.5%), had an ECOG performance score of 1 at baseline (62.5%) and were former smokers (50%). Best overall responses to magrolimab plus docetaxel in this population included CR or PR (20.8%), SD (37.5%) and PD (12.5%).

The ELEVATE-Lung&UC trial evaluated the safety, tolerability and effectiveness of magrolimab plus docetaxel in patients with metastatic NSCLC, metastatic small cell lung cancer and metastatic bladder cancer.

Patients with mNSCLC must have received one or two prior lines of platinum-based chemotherapy, a checkpoint inhibitor or both.

Patients received magrolimab at a priming dose of 1 milligram per kilogram (mg/kg) on cycle one day one, followed by a weekly dose of 30 mg/kg from cycle one day eight to cycle two day 15. After, patients received a maintenance dose of 60 mg/kg every three weeks from cycle three day one onward. Docetaxel was given at 75 mg per square meter every three weeks.

In February 2024, Gilead announced a global pause in enrollment to studies investigating magrolimab in patients with solid tumors, including ELEVATELung&UC, to review the risk-benefit profile of magrolimab across the trials. The FDA subsequently requested a partial clinical hold on these trials.

Gilead later decided to terminate the ELEVATELung&UC trial.

Reference:

“Biomarker analysis of magrolimab plus docetaxel in patients from ELEVATE-Lung and UC, a phase 2 multicohort study” by Nick van Buuren, et al., 2024 SITC Annual Meeting.

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