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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.
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
Abstracts by Kathleen N. Moore:
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