Safety findings from FORWARD II: A Phase 1b study evaluating the folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin (PLD), or pembrolizumab in patients (pts) with ovarian cancer.

Authors

null

David M. O'Malley

The Ohio State University College of Medicine, Columbus, OH

David M. O'Malley , Kathleen N. Moore , Ignace Vergote , Lainie P. Martin , Lucy Gilbert , Antonio Gonzalez Martin , Dale L. Nepert , Rodrigo Ruiz-Soto , Michael J. Birrer , Ursula A. Matulonis

Organizations

The Ohio State University College of Medicine, Columbus, OH, University of Oklahoma Health Sciences Center, Oklahoma City, OK, BGOG and University of Leuven, Leuven Cancer Institute, Leuven, Belgium, Fox Chase Cancer Center, Philadelphia, PA, McGill University Health Centre, Montréal, QC, Canada, Grupo Español de Investigación en Cáncer de Ovario (GEICO) and the University of Texas MD Anderson Cancer Center, Madrid, Spain, ImmunoGen, Inc., Waltham, MA, Massachusetts General Hospital, Boston, MA, Dana-Farber Cancer Institute, Boston, MA

Research Funding

Pharmaceutical/Biotech Company

Background: FORWARD II is a phase 1b study of the FRα-targeting ADC, mirvetuximab soravtansine (IMGN853), in combination with bevacizumab (BEV), carboplatin, PLD, or pembrolizumab in adults with FRα-positive EOC, primary peritoneal, or fallopian tube tumors (NCT02606305). Methods: The escalation stage of this trial evaluated the safety and tolerability of IMGN853 as part of 4 combination regimens: IMGN853 + BEV; + carboplatin; + PLD; and + pembrolizumab. IMGN853 was administered in combination on Day 1 of a 21 (BEV or carboplatin) or 28-day cycle (PLD). Pembrolizumab escalation is continuing. The starting dose of IMGN853 was 5 mg/kg (adjusted ideal body weight, AIBW), one level lower than the recommended single agent phase 2 dose (RP2D; 6 mg/kg AIBW) defined in a first-in-human study (NCT01609556). Adverse events (AEs) were evaluated by CTCAE v4.0. Results: 46 pts enrolled in the first 3 cohorts. IMGN853 was escalated from 5 to 6 mg/kg. Carboplatin and PLD dosing were escalated from AUC4 to AUC5 and 30 to 40 mg/m2, respectively; BEV dosing remained constant at 15 mg/kg. Diarrhea, nausea, and fatigue were common across cohorts (all grades; 33-57%) and mostly low grade (i.e. ≤ 2), consistent with the IMGN853 safety profile from the earlier phase I monotherapy study. AEs of interest related to the combination agents were seen in each arm. For example, grade 1/2 proteinuria (36%) and grade 3 hypertension (21%) were only observed in the BEV combination. Thrombocytopenia (44%) and neutropenia (39%), grades 1-3, occurred most frequently in the carboplatin arm. Grade 3 anemia and vomiting (each 14%), as well as low grade (≤ 2) constipation (43%), were seen in the PLD cohort. Conclusions: The RP2D dose of IMGN853 was readily combined with the highest doses (as per protocol) of BEV, carboplatin, and PLD. The AE profiles for these combinations were manageable and as expected based on known profiles of each agent; importantly, no new safety signals were identified. Updated data from all 4 combination regimens will be presented. Clinical trial information: NCT02606305

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Clinical Trial Registration Number

NCT02606305

Citation

J Clin Oncol 35, 2017 (suppl; abstr 5553)

DOI

10.1200/JCO.2017.35.15_suppl.5553

Abstract #

5553

Poster Bd #

375

Abstract Disclosures