Many patients have been treated with ADCs containing DM1 to targets other than CD37 without evidence of activity at such low dose levels and without neutropenia. In researching the neutropenia reported, it was found that, in the majority of the patients, it occurred shortly after the patient received the first dose of IMGN529 and was transient in nature, suggesting it was a manifestation of cytokine release. The study protocol was thus amended to include peri-infusional steroids as a prophylactic method. The abstract made public today includes favorable initial findings after this protocol change.IMGN853 Poster presentation: Saturday, May 31, 8:00-11:45am CT; Gynecologic Cancer Poster Session, S Hall A2, poster board #353. Abstract #5571: "Relationship of pharmacokinetics (PK), toxicity, and initial evidence of clinical activity with IMGN853, a folate receptor alpha (FRα)-targeting antibody drug conjugate in patients with epithelial ovarian cancer (EOC) and other FRα-positive solid tumors.” IMGN853 comprises a FRα-targeting antibody with the potent DM4 cytotoxic agent attached. This ADC is a potential treatment for FRα-positive solid tumors – which include many ovarian and endometrial cancers – and is currently in dose-finding Phase I clinical testing. As reported previously, dosing in the trial was changed from use of patient total body weight (TBW) to adjusted ideal body weight (AIBW) based on findings from PK modeling that AIBW should minimize inter-patient variability in IMGN853 blood levels. The data in the abstract made public today are from 30 patients treated with IMGN853 before the change from TBW to AIBW. As noted, 24 of these patients were treated at doses of 3.3 mg/kg or more, administered once every three weeks. This compares with 13 patients in the findings reported at ASCO in 2013 because of the treatment of additional patients at the 3.3 and/or 5.0 mg/kg dose levels. As disclosed in the abstract, preliminary evidence of clinical activity was observed in 10 of these 24 patients, with clinical activity defined as CA-125 response by CGIC criteria, stable disease lasting 18 or more weeks, and/or an objective response. It was observed that a quantifiable, minimum level of total exposure to IMGN853 was associated with evidence of anticancer activity. Clinical activity was seen in 5 of the 6 patients with ovarian cancer (serous or transitional EOC) and in 2 of the 4 patients with endometrial cancer whose IMGN853 exposure exceeded this level.
It was previously reported that the occurrence of its dose-limiting toxicity (DLT) was associated with IMGN853 blood levels exceeding definable thresholds. 1 That IMGN853 activity is associated with total exposure while its DLT is associated with peak exposure supports achievement of an appropriate therapeutic window and that dosing IMGN853 in smaller amounts more frequently may be preferable to once every three week dosing. Assessment of a modified weekly schedule was added to the ongoing Phase I trial earlier this year.Presentations on Partner Compounds In addition to multiple presentations on Kadcyla, data will be presented on the CD19-targeting ADC SAR3419 and the CD38-targeting antibody SAR650984, which are in development by Sanofi through a collaboration with ImmunoGen. Among the data made public today are findings from the STARLYTE Phase II trial showing SAR3419 therapy achieved a 43.9% objective response rate (ORR) when used as a single agent to treat relapsed/refractory diffuse large B-cell lymphoma; an objective of the study was to determine if it could achieve an ORR of at least 20%. Only grade 1-2 eye disorders were reported, including one patient with unrelated grade 2 keratitis. Abstract #8532 "A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma.”
- Poster presentation: Friday, May 30, 1:00-4:00 CT, S 405, poster board #12
- Oral abstract: Sunday, June 1, 10:12am-10:24am CT, E Hall D2
- Oral abstract: Monday, June 2, 8:48-9am CT, E354a