Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

Perets, Ruth; Bar, Jair; Rasco, Drew W.; Ahn, Myung‐Ju; Yoh, Kiyotaka; Kim, D.-W.; Nagrial, Adnan; Satouchi, Miyako; Lee, D.H.; Spigel, David R.; Kotasek, Dusan; Gutierrez, Martin; Niu, Jiaxin; Siddiqi, Shabana; Li, X.; Cyrus, Jobin; Chackerian, Alissa A.; Chain, Anne; Altura, Rachel A.; Cho, Byoung Chul

doi:10.1016/j.annonc.2020.11.020

Cited by 61 publications

(40 citation statements)

References 25 publications

(26 reference statements)

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“…Data indicate that the combination was generally well tolerated, with the observed toxicity within expectations based on previous studies [12,16,17]. The safety profile reported with quavonlimab plus pembrolizumab in SCLC was consistent with that reported with this regimen in NSCLC (Supplementary Table S3) [13]. The TRAE rate was 80% with the most frequent TRAEs being pruritus, fatigue, diarrhea, and hypothyroidism; no grade 4 or grade 5 TRAEs were reported.…”

Section: Discussionsupporting

confidence: 79%

“…In an ongoing phase II study of quavonlimab plus pembrolizumab in advanced solid tumors, this treatment combination demonstrated a tolerable safety profile [11,13]. Encouraging antitumor activity was observed in patients receiving first-line therapy for advanced non-small cell lung cancer (NSCLC) [13]. We report results for patients with extensive-stage small cell lung cancer (SCLC) receiving second-line or later therapy from the dose confirmation phase of this study.…”

Section: Introductionmentioning

confidence: 96%

“…Because of distinct and nonoverlapping mechanisms by which CTLA-4 and PD-1 are engaged by tumors to evade the immune system, combined blockade of both pathways is an attractive clinical strategy. CTLA-4 and PD-1/PD-L1 inhibitor combinations have shown clinical efficacy in various tumor types [4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Quavonlimab is a novel humanized immunoglobulin G1 monoclonal antibody that binds to CTLA-4 and blocks interactions with its ligands, CD80 and CD86 [13]. In an ongoing phase II study of quavonlimab plus pembrolizumab in advanced solid tumors, this treatment combination demonstrated a tolerable safety profile [11,13]. Encouraging antitumor activity was observed in patients receiving first-line therapy for advanced non-small cell lung cancer (NSCLC) [13].…”

Section: Introductionmentioning

confidence: 99%

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Anti–cytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer

et al. 2021

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This first-in-human phase I study (NCT03179436) investigated anti-cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody quavonlimab and anti-programmed death 1 monoclonal antibody pembrolizumab in patients with advanced solid tumors. The study was conducted in two parts: dose-escalation (part 1) and dose-confirmation (part 2). First-line treatment with quavonlimab + pembrolizumab conferred encouraging antitumor activity (objective response rate [ORR], 28%-40%) and was generally well tolerated (grade ≥ 3 treatment-related adverse events [TRAEs] were lowest with quavonlimab 25 mg every 6 weeks [Q6W] at 30% and highest with quavonlimab 75 mg Q3W at 57%) in non-small cell lung cancer. We present data from patients with extensive-stage small cell lung cancer (SCLC) receiving second-line or later therapy.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Anti–cytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer

et al. 2021

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“…For example, a combination of the anti-CTLA4 tremelimumab and the anti-PDL1 durvalumab is promising in advanced non-small cell lung cancer [ 2 ], head and neck squamous cell carcinoma [ 3 ], and other solid tumors such as advanced hepatocellular carcinoma [ 4 ]. The use of quavonlimab in combination with pembrolizumab in first-line treatment has also been reported in advanced non-small-cell lung cancer [ 5 ] and advanced small-cell lung cancer [ 6 ]. Recent studies have identified several new immune checkpoint targets, such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), and V-domain Ig suppressor of T cell activation (VISTA) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Renal Complications Related to Checkpoint Inhibitors: Diagnostic and Therapeutic Strategies

Béllière

Meyer

Chebane³

et al. 2021

Diagnostics

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Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have unprecedentedly improved global prognosis in several types of cancers. However, they are associated with the occurrence of immune-related adverse events. Despite their low incidence, renal complications can interfere with the oncologic strategy. The breaking of peripheral tolerance and the emergence of auto- or drug-reactive T-cells are the main pathophysiological hypotheses to explain renal complications after ICI exposure. ICIs can induce a large spectrum of renal symptoms with variable severity (from isolated electrolyte disorders to dialysis-dependent acute kidney injury (AKI)) and presentation (acute tubule-interstitial nephritis in >90% of cases and a minority of glomerular diseases). In this review, the current trends in diagnosis and treatment strategies are summarized. The diagnosis of ICI-related renal complications requires special steps to avoid confounding factors, identify known risk factors (lower baseline estimated glomerular filtration rate, proton pump inhibitor use, and combination ICI therapy), and prove ICI causality, even after long-term exposure (weeks to months). A kidney biopsy should be performed as soon as possible. The treatment strategies rely on ICI discontinuation as well as co-medications, corticosteroids for 2 months, and tailored immunosuppressive drugs when renal response is not achieved.

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Emerging therapeutic strategies for enhancing sensitivity and countering resistance to programmed cell death protein 1 or programmed death‐ligand 1 inhibitors in non–small cell lung cancer

Villaruz

Blumenschein

Leal

2023

Cancer

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The availability of agents targeting the programmed cell death protein 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) immune checkpoint has transformed treatment of advanced and/or metastatic non–small cell lung cancer (NSCLC). However, a substantial proportion of patients treated with these agents do not respond or experience only a brief period of clinical benefit. Even among those whose disease responds, many subsequently experience disease progression. Consequently, novel approaches are needed that enhance antitumor immunity and counter resistance to PD‐(L)1 inhibitors, thereby improving and/or prolonging responses and patient outcomes, in both PD‐(L)1 inhibitor‐sensitive and inhibitor‐resistant NSCLC. Mechanisms contributing to sensitivity and/or resistance to PD‐(L)1 inhibitors in NSCLC include upregulation of other immune checkpoints and/or the presence of an immunosuppressive tumor microenvironment, which represent potential targets for new therapies. This review explores novel therapeutic regimens under investigation for enhancing responses to PD‐(L)1 inhibitors and countering resistance, and summarizes the latest clinical evidence in NSCLC.

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Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

Cited by 61 publications

References 25 publications

Anti–cytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer

Anti–cytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody quavonlimab in combination with pembrolizumab: Safety and efficacy from a phase I study in previously treated extensive-stage small cell lung cancer

Renal Complications Related to Checkpoint Inhibitors: Diagnostic and Therapeutic Strategies

Emerging therapeutic strategies for enhancing sensitivity and countering resistance to programmed cell death protein 1 or programmed death‐ligand 1 inhibitors in non–small cell lung cancer

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