Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study

Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population...

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Veröffentlicht in:Journal of clinical oncology Jg. 35; H. 10; S. 1112
Hauptverfasser: Moore, Kathleen N, Martin, Lainie P, O'Malley, David M, Matulonis, Ursula A, Konner, Jason A, Perez, Raymond P, Bauer, Todd M, Ruiz-Soto, Rodrigo, Birrer, Michael J
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.04.2017
Schlagworte:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized - adverse effects
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents - adverse effects
Antineoplastic Agents - therapeutic use
Diarrhea - chemically induced
Disease-Free Survival
Drug Resistance, Neoplasm
Fallopian Tube Neoplasms - chemistry
Fallopian Tube Neoplasms - drug therapy
Fatigue - chemically induced
Female
Folate Receptor 1 - analysis
Folate Receptor 1 - antagonists & inhibitors
Humans
Hypotension - chemically induced
Immunoconjugates - adverse effects
Immunoconjugates - therapeutic use
Maytansine - adverse effects
Maytansine - analogs & derivatives
Maytansine - therapeutic use
Middle Aged
Nausea - chemically induced
Ovarian Neoplasms - chemistry
Ovarian Neoplasms - drug therapy
Peritoneal Neoplasms - chemistry
Peritoneal Neoplasms - drug therapy
Platinum Compounds - therapeutic use
Response Evaluation Criteria in Solid Tumors
Retreatment
Vision Disorders - chemically induced
ISSN:1527-7755, 1527-7755
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Zusammenfassung:Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1527-7755
1527-7755
DOI:10.1200/JCO.2016.69.9538