863P - A phase I study of mirvetuximab soravtansine (MIRV) and gemcitabine (G) in pts with selected FRα -positive solid tumours: Results in the endometrial cancer (EC) cohort

Background

Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, linked to the tubulin-disrupting maytansinoid DM4. MIRV has promising single agent activity in FRα-positive epithelial ovarian cancer (EOC), at 6 mg/kg, based on adjusted ideal body weight (AIBW) IV every (q) 21 days. Clinical data in other FRα-positive solid tumors has been limited. This study is evaluating MIRV and G in recurrent EOC, EC and triple negative breast cancer (TNBC). The recommended phase II dose (RP2D) reported at ASCO 2019, was established at DL3 (MIRV 6 mg/kg AIBW IV, day 1 and G 800 mg/m2 IV, d1, 8) q21 days. Here we report the results in the EC cohort treated at the RP2D.

Methods

Pts with FRα-positive EC with ≤ 2 prior chemotherapy (CT) regimens are eligible. FRα positivity by immunohistochemistry was initially defined as ≥25% of cells with PS2+ staining intensity (low to high FRα levels) and was subsequently revised to ≥ 50% of cells with PS2+ (medium/high FRα levels, with high defined as ≥ 75% of cells with PS2+). The expansion cohort of 12 pts with FRα-positive EC treated at the RP2D pre-specified that ≥ 2 responders are required to declare the combination promising.

Results

From October 2017 to May 2020, 55 EC pts underwent FRα screening, with 4 results pending. Out of 51 EC pts with results, 12 pts (23.5%) have medium/high FRα levels with 5 pts (9.8%) have low FRα level. 5 EC pts were treated at the RP2D (1 too early and 4 evaluable for response of which 1 pt had medium FRα and 3 pts had low FRα). 2 of the 4 evaluable EC pts at the RP2D achieved a partial response (PR). 1 PR was observed on cycle 7 (the only medium FRα level pt) and the second PR was on cycle 3. One pt. had SD after 4 cycles and remains on treatment, and 1 pt progressed in the 1^st cycle. Grade (G) 3-4 adverse events (AEs) in the 4 evaluable pts treated at the RP2D were infrequent and included: Gr 4 lymphopenia (1 pt), Gr 3 ANC/WBC/PLT (1 pt), and Gr 3 HTN and lymphopenia (1pt).

Conclusions

The combination of MIRV with G has promising clinical activity in FRα-positive EC. The regimen is tolerable with the expected treatment related AEs of these agents.

Clinical trial identification

NCT02996825.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by ImmunoGen, Inc and the Cancer Center Support Grant P30CA033572.

Disclosure

S. Glaser: Leadership role: Elsevier Radiation Onc. All other authors have declared no conflicts of interest.