Mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), in combination with carboplatin and bevacizumab: Initial results from a phase Ib study in patients (pts) with ovarian cancer

Abstract Background Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. MIRV is being evaluated in combination with carboplatin and bevacizumab (BEV) as part of the ongoing phase 1b study FORWARD II. Methods Eligible pts had platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer (platinum-free interval >6 months), 1 or 2 prior lines of therapy, and FRα positivity by immunohistochemistry (≥ 50% of tumor cells with at least moderate staining intensity). MIRV was administered at 6 mg/kg (adjusted ideal body weight) in combination with carboplatin (AUC 5) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. MIRV and BEV were continued as maintenance after completing carboplatin. Responses were assessed with RECIST 1.1 and adverse events (AEs) by CTCAE v4.03. Results Forty-one pts received full dosing of the triplet combination, with a median of 9 cycles each of MIRV (range, 3-16) and BEV (1-18) and 6 cycles of carboplatin (3-8) at the time of interim analysis; 31 pts remain on study. Low grade diarrhea (all grades, 76%; [grade 3, 7%]), nausea (68%; [2%]), and fatigue (59%; [5%]), the most common treatment-emergent AEs, were consistent with the safety profile of MIRV as monotherapy, albeit more frequent. AEs typically associated with carboplatin (thrombocytopenia [39% ≥ grade 3] and neutropenia [20% ≥ grade 3]) and BEV (hypertension [27% grades 1-3]) were also observed. To date, no deaths have occurred. The confirmed objective response rate was 80%, including 7 complete responses and 26 partial responses. With a median follow-up time of 6.8 months, progression-free survival data are immature. Conclusions Full dose MIRV was readily combined with standard dosing for both BEV and carboplatin, with a manageable AE profile as anticipated for a combination of these three agents. No new safety signals have been identified. The preliminary signals of clinical activity are encouraging and justify further exploration of this novel therapeutic combination. Clinical trial identification NCT02606305. Legal entity responsible for the study ImmunoGen, Inc. Funding ImmunoGen, Inc. Disclosure D. O'Malley: Advisory / Consultancy: Agenus; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: OncoQuest; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Ambry; Advisory / Consultancy: Clovis; Advisory / Consultancy: Janssen; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Novocure; Advisory / Consultancy: Regeneron; Advisory / Consultancy: Myriad. L. Gilbert: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Roche; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Astex Pharmaceuticals; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): ImmunoGen. C. Castro: Advisory / Consultancy: N-of-One; Advisory / Consultancy: Advanced Medical; Advisory / Consultancy: InfiniteMD; Research grant / Funding (institution): ImmunoGen; Licensing / Royalties: Exosome Diagnostics. U.A. Matulonis: Advisory / Consultancy: ImmunoGen Inc; Advisory / Consultancy: Fujifilm; Advisory / Consultancy: Geneos; Advisory / Consultancy: 2X Oncology; Advisory / Consultancy: Mersana; Advisory / Consultancy: Merck. K. Malek: Full / Part-time employment: ImmunoGen Inc. K.N. Moore: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Aravive; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy: OncoMed. All other authors have declared no conflicts of interest.