Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic urothelial carcinoma from the JAVELIN solid tumor phase 1b trial: Analysis of safety, clinical activity, and PD-L1 expression.

Apolo, Andrea B.; Infante, Jeffrey R.; Hamid, Omid; Patel, Manish R.; Wang, Ding; Kelly, Karen; Mega, Anthony; Britten, Carolyn D.; Ravaud, Alain; Mita, Alain C.; Safran, Howard; Stinchcombe, Tom; Grote, H.; Heydebreck, Anja von; Cuillerot, Jean-Marie; Gulley, James L.

doi:10.1200/jco.2016.34.15_suppl.4514

Cited by 30 publications

(25 citation statements)

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“…1, 2 Avelumab, an anti-PD-L1 MAb, has demonstrated clinical activity in studies in patients with a range of human cancers; 3-11 it has just been approved by the Food and Drug Administration for the treatment of Merkel cell and bladder carcinoma, and is in several Phase III studies in other indications. Despite the clinical success with anti-PD-1/PD-L1 MAbs, the majority of patients with carcinomas do not derive clinical benefit from these agents.…”

Section: Introductionmentioning

confidence: 99%

ADCC employing an NK cell line (haNK) expressing the high affinity CD16 allele with avelumab, an anti-PD-L1 antibody

et al. 2017

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NK-92 cells, and their derivative, designated aNK, were obtained from a patient with non-Hodgkin lymphoma. Prior clinical studies employing adoptively transferred irradiated aNK cells have provided evidence of clinical benefit and an acceptable safety profile. aNK cells have now been engineered to express IL-2 and the high affinity (ha) CD16 allele (designated haNK). Avelumab is a human IgG1 anti–PD-L1 monoclonal antibody, which has shown evidence of clinical activity in a range of human tumors. Prior in vitro studies have shown that avelumab has the ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells when combined with NK cells. In the studies reported here, the ability of avelumab to enhance the lysis of a range of human carcinoma cells by irradiated haNK cells via the ADCC mechanism is demonstrated; this ADCC is shown to be inhibited by anti-CD16 blocking antibody and by concanamycin A, indicating the use of the granzyme/perforin pathway in tumor cell lysis. Studies also show that while NK cells have the ability to lyse aNK or haNK cells, the addition of NK cells to irradiated haNK cells does not inhibit haNK-mediated lysis of human tumor cells, with or without the addition of avelumab. Avelumab-mediated lysis of tumor cells by irradiated haNK cells is also shown to be similar to that of NK cells bearing the V/V Fc receptor high affinity allele. These studies thus provide the rationale for the clinical evaluation of the combined use of avelumab with that of irradiated adoptively transferred haNK cells.

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Section: Introductionmentioning

confidence: 99%

ADCC employing an NK cell line (haNK) expressing the high affinity CD16 allele with avelumab, an anti-PD-L1 antibody

et al. 2017

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“…Based on these results, MPDL3280A received breakthrough designation by the FDA in June 2014. Recently, several other immunotherapies agents such nivolumab [56], pembrolizumab [57], avelumab [58] or durvalumab [59] have shown promising data in different phase I/II trials; and a phase II trial with atezolizumab in platinum-treated patients showed an ORR 16% (28% IC2/3 PDL1 subgroup) and an overall survival of 7.9 months (11.9 IC2/3 PDL1 subgroup) [60]. Another multiple PD-1/PDL-1 agents are currently being tested alone or in combination in advanced/refractory UC.…”

Section: First-line Therapy Of Locally Advanced and Metastatic Diseasementioning

confidence: 99%

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016)

et al. 2016

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The goal of this article is to provide recommendations for the diagnosis and treatment of muscle-invasive and metastatic bladder cancer. The diagnosis of muscle-invasive bladder cancer is made by pathologic evaluation after transurethral resection. Recently, a molecular classification has been proposed. Staging of muscle-invasive bladder cancer must be done by computed tomography scans of the chest, abdomen and pelvis and classified on the basis of UICC system. Radical cystectomy and lymph node dissection are the treatment of choice. In muscle-invasive bladder cancer, neoadjuvant chemotherapy should be recommended in patients with good performance status and no renal function impairment. Although there is insufficient evidence for use of adjuvant chemotherapy, its use must be considered when neoadjuvant therapy had not been administered in high-risk patients. Multimodality bladder-preserving treatment in localized disease is an alternative in selected and compliant patients for whom cystectomy is not considered for clinical or personal reasons. In metastatic disease, the first-line treatment for patients must be based on cisplatin-containing combination. Vinflunine is the only drug approved for use in second line in Europe. Recently, immunotherapy treatment has demonstrated activity in this setting.

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“…Results from the phase Ib trial for patients with platinum-refractory disease or who are ineligible for cisplatin-based chemotherapy demonstrated an overall response rate (ORR) of 18.2% that consisted of 2 complete responses and 6 partial responses after treatment with avelumab. 61 A higher progression-free survival was seen in patients with positive PD-L1 tumor cells versus patients that did not express PD-L1 (58.3% vs 16.6% at 24 weeks), although some patients who were PD-L1-negative did experience a response to treatment.…”

Section: Targeted Immunotherapymentioning

confidence: 92%

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016

Clark

Spiess

Agarwal

et al. 2016

J Natl Compr Canc Netw

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These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.

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Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic urothelial carcinoma from the JAVELIN solid tumor phase 1b trial: Analysis of safety, clinical activity, and PD-L1 expression.

Cited by 30 publications

References 0 publications

ADCC employing an NK cell line (haNK) expressing the high affinity CD16 allele with avelumab, an anti-PD-L1 antibody

ADCC employing an NK cell line (haNK) expressing the high affinity CD16 allele with avelumab, an anti-PD-L1 antibody

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016)

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016

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