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Clinical Trial
. 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

Kathleen N Moore  1 , Hossein Borghaei  2 , David M O'Malley  3 , Woondong Jeong  4 , Shelly M Seward  5 , Todd M Bauer  6 , Raymond P Perez  7 , Ursula A Matulonis  8 , Kelli L Running  9 , Xiaoyan Zhang  9 , Jose F Ponte  9 , Rodrigo Ruiz-Soto  9 , Michael J Birrer  10
Affiliations
Clinical Trial

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

Kathleen N Moore et al. Cancer. .

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.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

Kathleen N. Moore reports honoraria for advisory board service from AstraZeneca, Clovis, Immunogen, and Genentech/Roche; service on the Tesaro steering committee; and service on the Advaxis steering committee/advisory board outside the submitted work. Hossein Borghaei reports personal fees from and service on the advisory boards of Genentech, Lilly, Bristol-Myers-Squibb, Celgene, and Clovis; personal fees from AstraZeneca, Pfizer, Merck, EMD-Serono, and Trovagene; and clinical trial funding from Merck/Celgene and Millennium outside the submitted work. David M. O’Malley reports personal fees from Clovis, Janssen, AstraZeneca, Genentech/Roche, Amgen, and Eisai outside the submitted work. Shelly M. Seward reports service on the AstraZeneca Speakers’ Bureau. Ursula A. Matulonis reports service on the advisory boards of AstraZeneca, Clovis, Eli Lilly, Genentech, and Immunogen outside the submitted work. Kelli L. Running reports employment at ImmunoGen. Xiaoyan Zhang reports employment at ImmunoGen. Jose F. Ponte reports employment at ImmunoGen and has a patent pending (US. Pub. no. 2015 of 0132323; International Pub. no. WO2015 of 054400). Rodrigo Ruiz-Soto reports employment at ImmunoGen. Woondong Jeong, Todd M. Bauer, Raymond P. Perez, and Michael J. Birrer made no disclosures.

Figures

Figure 1.
Figure 1.
Mean concentration-time profiles are illustrated in cycles 1 and 3 after infusion of mirvetuximab soravtansine on dosing schedule of once every 3 weeks. All doses listed are in mg/kg and were calculated based on total body weight (TBW) or adjusted ideal body weight (AIBW), as indicated.
Figure 2.
Figure 2.
The activity of mirvetuximab soravtansine in a patient who had platinum-resistant ovarian cancer reveals a partial response.
See this image and copyright information in PMC

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