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Cancer. 2017 Aug 15;123(16):3080-3087. doi: 10.1002/cncr.30736. Epub 2017 Apr 25.

Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors.

Author information

1
Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
2
Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
3
Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio.
4
Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, Texas.
5
Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
6
Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, Tennessee.
7
Division of Hematology/Oncology, University of Kansas, Fairway, Kansas.
8
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
9
ImmunoGen, Inc., Waltham, Massachusetts.
10
Gillette Center for Gynecologic Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Abstract

BACKGROUND:

Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors.

METHODS:

Patients received IMGN853 on day 1 of a 21-day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose-limiting toxicity or progression. Dose escalation commenced in single-patient cohorts for the first 4 planned dose levels and then followed a standard 3 + 3 scheme. The primary objectives were to determine the maximum tolerated dose and the recommended phase 2 dose. Secondary objectives were to determine safety and tolerability, to characterize the pharmacokinetic profile, and to describe preliminary clinical activity.

RESULTS:

In total, 44 patients received treatment at doses escalating from 0.15 to 7.0 mg/kg. No meaningful drug accumulation was observed with the dosing regimen of once every 3 weeks. The most common treatment-related adverse events were fatigue, blurred vision, and diarrhea, the majority of which were grade 1 or 2. The dose-limiting toxicities observed were grade 3 hypophosphatemia (5.0 mg/kg) and grade 3 punctate keratitis (7.0 mg/kg). Two patients, both of whom were individuals with epithelial ovarian cancer, achieved confirmed tumor responses according to Response Evaluation Criteria in Solid Tumors 1.1, and each was a partial response.

CONCLUSIONS:

IMGN853 demonstrated a manageable safety profile and encouraging preliminary clinical activity, particularly in patients with ovarian cancer. The results establish a recommended phase 2 dosing of 6.0 mg/kg (based on adjusted ideal body weight) once every 3 weeks. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3080-7. © 2017 American Cancer Society.

KEYWORDS:

antibody-drug conjugate; clinical trial; folate receptor; phase 1; targeted therapy

PMID:
28440955
DOI:
10.1002/cncr.30736
[Indexed for MEDLINE]
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