1359TiP RELATIVITY-104: First-line relatlimab (RELA) + nivolumab (NIVO) with chemotherapy vs nivo with chemotherapy in stage IV or recurrent non-small cell lung cancer (NSCLC): A phase II, randomized, double-blind study

Morgensztern, Daniel; Chaudhry, Arvind; Iannotti, Nicholas; Acevedo, A.; Balaburski, Gregor M.; Balogh, Agnès; Peters, Solange

doi:10.1016/j.annonc.2021.08.1960

Cited by 5 publications

(2 citation statements)

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“…LAG-3 is a key immune checkpoint currently being investigated as an I-O therapy for patients with solid tumors and hematological malignancies. [13,16,18,21,[24][25][26] The development of a robust LAG-3 IHC assay will enable the analysis of IC LAG-3 status in the tumor microenvironment and the correlation between LAG-3 expression status and response to LAG-3-directed oncology treatments. A robust LAG-3 IHC assay that is suitable for clinical trials and clinical use for melanoma is described in this work.…”

Section: Discussionmentioning

confidence: 99%

Development of a LAG-3 Immunohistochemistry Assay for Melanoma

Johnson

McCune

Locke

et al. 2022

Preprint

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Aims: A robust immunohistochemistry (IHC) assay was developed to detect lymphocyte activation gene 3 (LAG-3) expression by immune cells (ICs) in tumor tissues. LAG-3 is an immuno-oncology target with demonstrable clinical benefit, and there is a need for a standardized, well-characterized assay to measure its expression. This study aims to describe LAG-3 scoring criteria and present the specificity, sensitivity, analytical precision, and reproducibility of this assay. Methods: The specificity of the assay was investigated by antigen competition and with LAG3 knockout cell lines. A melanin pigment removal procedure was implemented to prevent melanin interference in IHC interpretation. Formalin-fixed, paraffin-embedded (FFPE) human melanoma samples with a range of LAG-3 expression levels were used to assess the sensitivity and analytical precision of the assay with a ≥1% cutoff to determine LAG-3 positivity. Interobserver and intraobserver reproducibility were evaluated with 60 samples in intralaboratory studies and 70 samples in interlaboratory studies. Results: The LAG-3 IHC method demonstrated performance suitable for analysis of LAG-3 IC expression in clinical melanoma samples. The pretreatment step effectively removed melanin pigment that could interfere with interpretation. LAG-3 antigen competition and analysis of LAG3 knockout cell lines indicated that the 17B4 antibody clone binds specifically to LAG-3. The intrarun repeatability, interday, interinstrument, interoperator, and interreagent lot reproducibility demonstrated a high scoring concordance (>95%). The interobserver and intraobserver reproducibility and overall interlaboratory and intralaboratory reproducibility also showed high scoring concordance (>90%). Conclusions: We have demonstrated that the assay reliably assesses LAG-3 expression in FFPE human melanoma samples by IHC.

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Section: Discussionmentioning

confidence: 99%

Development of a LAG-3 Immunohistochemistry Assay for Melanoma

Johnson

McCune

Locke

et al. 2022

Preprint

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“…Inhibitors of LAG-3 have already reached phase II and phase III clinical trials and relatlimab has been approved in combination with nivolumab for advanced melanoma [157]. In NSCLC, the RELATIVITY study has commenced accrual and is exploring the combination of relatlimab and nivolumab and chemotherapy in the advanced setting [158].…”

Section: Future Outlook For the Use Of Immunotherapy In Nsclcmentioning

confidence: 99%

Immunotherapy through the Lens of Non-Small Cell Lung Cancer

Stanley

Flanagan

Reilly

et al. 2023

Cancers

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Immunotherapy has revolutionised anti-cancer treatment in solid organ malignancies. Specifically, the discovery of CTLA-4 followed by PD-1 in the early 2000s led to the practice-changing clinical development of immune checkpoint inhibitors (ICI). Patients with lung cancer, including both small cell (SCLC) and non-small cell lung cancer (NSCLC), benefit from the most commonly used form of immunotherapy in immune checkpoint inhibitors (ICI), resulting in increased survival and quality of life. In NSCLC, the benefit of ICIs has now extended from advanced NSCLC to earlier stages of disease, resulting in durable benefits and the even the emergence of the word ‘cure’ in long term responders. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Patients may also develop immune-related toxicity, a small percentage of which is associated with significant mortality and morbidity. This review article highlights the various types of immunotherapeutic strategies, their modes of action, and the practice-changing clinical trials that have led to the widespread use of immunotherapy, with a focus on ICIs in NSCLC and the current challenges associated with advancing the field of immunotherapy.

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