Avelumab (MSB0010718C; anti-PD-L1) vs platinum-based doublet as first-line treatment for metastatic or recurrent PD-L1-positive non-small-cell lung cancer: The phase 3 JAVELIN Lung 100 trial.

Reck, Martin; DeGreen, Hyatt P.; Rose, Andrea L.; Pavlakis, Nick; Derjcke, Sofie Maria; Radić, Jasna; Jeppesen, Nina; Thomas, Michael; Losonczy, György; Kalinka-Warzocha, Ewa; Dreosti, Lydia; Özgüroǧlu, Mustafa; Postmus, Pieter E.; Helwig, Christoph; Chand, Vikram K.; Cuillerot, Jean-Marie; Westeel, Virginie

doi:10.1200/jco.2016.34.15_suppl.tps9105

Cited by 8 publications

(4 citation statements)

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“…In this respect, a randomised phase III trial is currently ongoing to evaluate the role of avelumab in the first line treatment of metastatic NSCLC with high PD-L1 expression. 22 Several studies have evaluated EGFR blockade in NSCLC patients. Two phase III trials, the First-Line ErbituX in lung cancer (FLEX) and the BMS-099, that were investigating the addition of cetuximab to standard chemotherapy in the first line setting, had contradictory results.…”

Section: Discussionmentioning

confidence: 99%

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Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer

et al. 2020

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BackgroundAntibody-dependent cell-mediated cytotoxicity (ADCC) may mediate antitumour activity of IgG1-isotype monoclonal antibody (mAb), suggesting as potential treatment combination of IgG1-mAbs, anti-epidermal growth factor receptor cetuximab and anti-programmed death-ligand-1 avelumab.MethodsWe evaluated ADCC induction in lung cancer cells by lactate dehydrogenase (LDH) release assay. Antitumour activity and safety of cetuximab plus avelumab were explored in a single-arm proof-of-concept study in pre-treated non-small cell lung cancer (NSCLC) patients (pt) (Cetuximab-AVElumab-lung, CAVE-Lung). Search for predictive biomarkers of response was done.ResultsAvelumab plus cetuximab induced ADCC in NSCLC cells in vitro in presence of natural killers (NK) from healthy donors (HD) or NSCLC pt, as effectors. Sixteen relapsed NSCLC pt were treated with avelumab plus cetuximab. Antitumour activity was observed in 6/16 pt, defined by progression free survival (PFS) ≥8 months, with 4 of them still on treatment at data lock time (range, 14–19 months). Of note, 3/6 responders had received as previous line anti-programmed death-1 therapy. In responders, clinical benefit was accompanied by significant increase in LDH release over baseline at the first radiological evaluation (8 weeks) (p=0.01) and by early skin toxicity; while in the 10 non-responders, that had PFS ≤5 months, LDH release tends to reduce. Baseline circulating DNA levels were higher in non-responders compared with responders and HD (p=0.026) and decrease in responders during therapy. Mutations in DNA damage responsive family genes were found in responders.ConclusionCetuximab and avelumab activates NSCLC pt NK cells. Ex vivo evaluation of ADCC, circulating DNA levels and early skin toxicity may predict response to cetuximab plus avelumab in NSCLC.EUDRACT 2017-004195-58

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Section: Discussionmentioning

confidence: 99%

“…In this respect, a randomised phase III trial is currently ongoing to evaluate the role of avelumab in the first line treatment of metastatic NSCLC with high PD-L1 expression. 22 …”

Section: Discussionmentioning

confidence: 99%

Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer

et al. 2020

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“…[94,95] The JAVELIN Lung 100 trial [NCT02576574], a phase III, open-label, multicenter trial of avelumab (an anti-PD-L1 antibody) compared with platinum-based doublet chemotherapy as first-line treatment for recurrent or stage IV NSCLC with PD-L1 expression positive and without EGFR mutation and ALK translocation. [96] Although the JAVELIN Lung 200 trial reported that the avelumab group did not show improved OS in PD-L1-positive patients with platinum treatment compared to the chemotherapy group, the trial had a favorable safety profile. [97] Will avelumab be a new option for NSCLC without EGFR/ALK mutations?…”

Section: Challenges and Prospects In The Futurementioning

confidence: 99%

Advances and challenges of first-line immunotherapy for non-small cell lung cancer: A review

Guo,

Zhang,

Qin

et al. 2024

Medicine

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The current use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has dramatically changed the clinical strategy for metastatic non-small cell lung cancer (mNSCLC). As a result of great achievements in clinical trials, 6 programmed death-1 inhibitors (sintilimab, camrelizumab, tislelizumab, pembrolizumab, cemiplimab, and nivolumab), 2 programmed death-ligand 1 inhibitors (sugemalimab and atezolizumab), and 1 cytotoxic T lymphocyte-associated antigen-4 inhibitor (ipilimumab) have been approved as first-line treatment for mNSCLC by the US Food and Drug Administration. Recently, research on ICIs has shifted from a large number of second-line to first-line settings in clinical trials. Results from first-line trials have shown that almost all driver-negative mNSCLC are treated with ICIs and significantly prolong patient survival; however, the low response rate and adverse reactions to immunotherapy remain to be addressed. Here, we summarize the use of ICIs, including monotherapy and combination therapy, in the first-line treatment of mNSCLC in recent years and discuss the low response rate and adverse reactions of ICIs as well as the challenges and expectations for the first-line treatment of mNSCLC in the future.

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“…Preliminary findings (data cutoff, October 23, 2015) of the 75 patients who were followed up for a minimum of 3 months revealed an ORR of 18.7% (95% CI 10.6-29.3), with 1 complete response, 13 partial responses, and 34 patients with stable disease, for a disease control rate of 64.0% [58]. On the back of these findings, avelumab monotherapy is currently being compared with docetaxel as first-line therapy in patients with PD-L1-expressing NSCLC in the phase III JAVELIN Lung 100 trial (NCT02576574) [59], and as second-line therapy in the phase III JAVELIN Lung 200 trial (NCT02395172).…”

Section: Keynote-021mentioning

confidence: 99%

PD-1 blockade in advanced NSCLC: A focus on pembrolizumab

Peters

Kerr

Stahel

2018

Cancer Treatment Reviews

106

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Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers and is responsible for a large proportion of all cancer-related deaths. Current treatment options are inadequate, reflecting a substantial unmet clinical need. Increasing knowledge regarding the mechanisms and genetic aberrations underlying tumor development and growth has heralded a new era of therapy in oncology, moving away from indiscriminate cytotoxic chemotherapy toward more finely focused, targeted medicine. The development of small-molecule drugs and monoclonal antibodies directed toward specific components of dysfunctional molecular or immune pathways, and mutated genes specific to particular cancer types, is leading the field to more personalized and less toxic treatment options, many of which have demonstrated greater efficacy and survival benefits than their chemotherapeutic counterparts. Particularly successful examples are agents that interfere with the programmed death 1 (PD-1) pathway, which many tumors can hijack to avoid immune surveillance and editing. Pembrolizumab, a monoclonal antibody directed at PD-1 that blocks the engagement between PD-1 and its ligands, has been explored as a treatment for solid tumors, and demonstrated survival benefits in several studies. The use of PD-1 inhibitors such as nivolumab and pembrolizumab in advanced cancers is widespread, and pembrolizumab is available in more than 60 countries for at least one of the following: advanced melanoma, PD-L1-expressing NSCLC, head and neck squamous cell carcinoma, and adult and pediatric patients with refractory classical Hodgkin's lymphoma. This work provides a brief overview of the role of pembrolizumab in the treatment of advanced (recurrent/metastatic) NSCLC.

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Avelumab (MSB0010718C; anti-PD-L1) vs platinum-based doublet as first-line treatment for metastatic or recurrent PD-L1-positive non-small-cell lung cancer: The phase 3 JAVELIN Lung 100 trial.

Cited by 8 publications

References 0 publications

Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer

Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer

Advances and challenges of first-line immunotherapy for non-small cell lung cancer: A review

PD-1 blockade in advanced NSCLC: A focus on pembrolizumab

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