Zimberelimab plus lenvatinib showed immune rechallenge effects in 30 patients with advanced cervical cancer.
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Key Takeaway
Note that immune rechallenge with zimberelimab plus lenvatinib altered T cell phenotypes in a small cohort of cervical cancer patients.
This multicenter, single-arm, phase II trial enrolled 30 patients with advanced cervical cancer who experienced disease progression on or after prior ICI therapy. The intervention was a combined regimen of zimberelimab and lenvatinib, representing an immune rechallenge strategy. No comparator group was included in this study design.
The main results focused on immunologic markers rather than traditional efficacy endpoints. In responders, immune rechallenge induced a more cytotoxic phenotype in CD8+ T cells. Responders also showed more effector memory CD8+ T cells and reduced exhausted CD8+ T cells after treatment. The population of CD45+CD3+Lyz+ dyad cells correlated with clinical benefit. In nonresponders, natural killer-like CD8+ T and progenitor-exhausted CD8+ T phenotypes were observed in the blood.
Safety and tolerability data were not reported in this publication. The study had inherent limitations including its single-arm trial design and small sample size of 30 patients. Follow-up duration was not reported. These factors limit the ability to draw firm conclusions about clinical outcomes.
The practice relevance underscores potential feasibility of immune rechallenge. Spatiotemporal genomic and immunologic alterations are critical treatment biomarkers to identify responders. The efficacy of retreatment with ICIs is controversial, and relapse remains common in this setting.
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View Original Abstract ↓
UNLABELLED: Although immune checkpoint inhibitors (ICI) show durable responses in various cancers, relapse remains common. The efficacy of retreatment with ICIs is controversial. We conducted a multicenter, single-arm, phase II trial (NCT05824468), including 30 patients with advanced cervical cancer who experienced disease progression on or after prior ICI therapy. Participants received a combined regimen of zimberelimab and lenvatinib (immune rechallenge). Single-cell multiomics analysis of sequential biopsies of relapsed tumors and blood samples showed that immune rechallenge induced a more cytotoxic phenotype in CD8+ T cells in responders, whereas a natural killer-like CD8+ T and progenitor-exhausted CD8+ T phenotype was observed in the blood of nonresponders. In tumors, responders showed more effector memory CD8+ T cells and reduced exhausted CD8+ T cells after treatment. A population of CD45+CD3+Lyz+ dyad cells, composed of T cells and myeloid cells, was correlated with clinical benefit. Our findings proved that immune rechallenge could be an effective treatment for patients with advanced cervical cancer whose disease progressed on or after prior ICI therapy.
SIGNIFICANCE: This study highlights response heterogeneity within patients with advanced cervical cancer with progressive disease on prior ICIs to immune rechallenge and underscores its potential feasibility. Spatiotemporal genomic and immunologic alterations are critical treatment biomarkers to identify responders in future clinical practice.
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