150377-156

Preliminary single agent activity of IMGN853, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in platinum-resistant epithelial ovarian cancer (EOC) patients (pts): Phase I trial.

Subcategory: 
Category: 
Gynecologic Cancer
Session Type and Session Title: 
Poster Discussion Session, Gynecologic Cancer
Abstract Number: 

5518

Poster Board Number: 
Board #76
Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 5518)
Author(s): 
Kathleen N. Moore, Lainie P. Martin, Shelly Marie Seward, Todd Michael Bauer, David M. O'Malley, Raymond P. Perez, Amit M. Oza, Woondong Jeong, Maurice William Kirby, Yinghui Zhou, Mary F. Michenzie, Joseph Ponte, Rodrigo Ruiz-Soto, Michael J. Birrer; University of Oklahoma Health Sciences Center, Oklahoma City, OK; Fox Chase Cancer Ctr, Philadelphia, PA; Wayne State Univ- Karmanos Cancer Inst, Huntington Woods, MI; Sarah Cannon Research Institute / Tennessee Oncology, PLLC., Nashville, TN; The Ohio State University College of Medicine, Columbus, OH; University of Kansas, Fairway, KS; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Westchester Hem/Onc Grp, Westchester, NY; ImmunoGen Inc, Waltham, MA; Immunogen, Waltham, MA; ImmunoGen Inc, Dedham, MA; ImmunoGen, Waltham, MA; Massachusetts General Hospital/Dana Farber Cancer Center, Boston, MA

Abstract Disclosures

Abstract: 

Background: IMGN853 (mirvetuximab soravtansine) is a FRα-targeting ADC that comprises a FRα-binding antibody conjugated with the potent maytansinoid, DM4. Methods: This phase I trial evaluates the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of IMGN853 in pts with FRα-positive solid tumors. A recommended phase II dose (RP2D) of 6.0 mg/kg, administered once every three weeks using adjusted ideal body weight was established in the dose-finding phase. Preliminary evidence of antitumor activity is being investigated at the RP2D in disease-specific cohorts of pts with platinum-resistant EOC and relapsed/refractory endometrial carcinoma. Here we report preliminary clinical activity (partial PR or complete CR response, CA125 response, SD ≥ 6 cycles) at the RP2D in pts with platinum-resistant EOC. Results: To date, 14 platinum-resistant EOC pts have been treated at the RP2D: 2 in dose escalation; 12 in the expansion cohort. All pts were heavily pretreated (mean: 4.5; range 2-12 prior treatments), all had prior taxane exposure, and all had progressed on their most recent regimen. All pts had FRα-positive tumor expression by IHC in archival tissue. Clinical benefit was observed in 5 /10 evaluable patients (4 have not reached 1st assessment): 4 PRs and 1 confirmed CA125 response, for an objective response rate (ORR) of 40% and clinical benefit rate (CBR) of 50%. In each pt with a PR, tumor regression had begun early on treatment (cycle 2 evaluation). Shrinkage of visceral metastases was seen: a PR pt had a 45% reduction in a 5 cm liver mass. One additional pt had an unconventional response: the disappearance of a non-target lesion with development of new lesions. The majority of adverse events (AEs) were CTCAE grade 1 or 2, with diarrhea, ocular events, cough, fatigue, decreased appetite, neuropathy and nausea reported in > 20 % of pts. Nine of the 14 pts remain on study; enrollment continues. Conclusions: IMGN853 demonstrates promising preliminary clinical activity with an ORR of 40% and CBR of 50%, in heavily pretreated platinum-resistant ovarian cancer pts with a manageable AE profile. Clinical trial information: NCT01609556