dm+d

Unassigned

New Medicines

Ovarian cancer, platinum-resistant epithelial (EOC) - monotherapy

Information

New molecular entity
ImmunoGen
ImmunoGen

Development and Regulatory status

None
Phase III Clinical Trials
Pre-registration (Filed)
Yes
Yes
May 22 FDA has accepted and filed BLA. The application has been granted Priority Review designation and FDA has set PDUFA action date of November 28, 2022
Mar 22ImmunoGen have submitted a biologics license application to the FDA for mirvetuximab soravtansine to treat pts with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer previously treated with 1 to 3 prior systemic treatments. The submission is based on results from the pivotal PIII SORAYA trial [13]
Nov 21ImmunoGen plan to file in US in Q1 22 [12].
Mar 20ImmunoGen currently intends to commercialize mirvetuximab soravtansine itself in the US and European Union, but at this time, does not have any significant direct sales, marketing or distribution capabilities [11].
Dec 19Based on FDA advice, ImmunoGen will initiate the SORAYA trial to support the accelerated approval of mirvetuximab soravtansine. The trial will evaluate mirvetuximab monotherapy in women with folate receptor alpha (FRa)-high platinum-resistant ovarian cancer who have been previously treated with bevacizumab [8].
Dec 19Company plans to file in the US for accelerated approval in H2 21. The SORAYA trial will start Apr 20 [8].
Nov 19ImmunoGen has met with the US FDA to discuss the design of the planned PIII MIRASOL trial of mirvetuximab soravtansine for platinum-resistant ovarian cancer patients whose tumours express high levels of folate receptor alpha. The company intends to enrol first patient in the study by end of 2019 [8].
May 19ImmunoGen intends to meet with the EMA, to discuss the possibility of securing a conditional marketing authorisation for mirvetuximab soravtansine, for treatment of platinum-resistant ovarian cancer patients with high FRa expression [8].
May 19Following failure of the PIII FORWARD I trail to meet its primary efficacy endpoint, the FDA has requested that ImmunoGen conduct a further PIII clinical trial [7]
Jun 18Granted fast-track designation in US [4].
Apr 15Mirvetuximab soravtansine granted orphan drug designation for treatment of ovarian cancer in the EU.[2]
Aug 14Mirvetuximab soravtansine granted orphan drug designation for treatment of ovarian cancer in the USA.[2]

Category

Humanised monoclonal antibody which targets the folate 1 receptor to deliver the cytotoxic agent; maytansinoid DM4 via a sulfo-SPDB cleavable linker.
Around 7,300 women are diagnosed with ovarian cancer in the UK each year. [1]
Ovarian cancer, platinum-resistant epithelial (EOC) - monotherapy
Intravenous

Trial or other data

Mar 22Results of MIRASOL trial are due in Q3 22 [14].
Mar 22 In PIII (n=106) trial where all participants had previously received Avastin and 50% had received a PARP inhibitor, median progression-free survival (mPFS) was 4.3 months when assessed by the investigator and 5.5 months when assessed by blinded independent central review [14].
Nov 21 ImmunoGen announce mirvetuximab achieved a 32% ORR regardless of whether a patient had received a PARP inhibiot and independent of number of lines of therapy. In addition to achieving its primary endpoint the study reported a median duration of response of 5.9 months [12].
Dec 20In its 2019 annual report, Immunogen states that following the results of FORWARD I, it undertook a comprehensive analysis of the data from the trial to determine which patients will benefit most from mirvetuximab and how best to identify those patients. With the outputs from these analyses, it engaged with the FDA resulting in the design of SORAYA, a new pivotal trial to evaluate mirvetuximab monotherapy in women with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer who have received up to three prior regimens and have been previously treated with bevacizumab. SORAYA will enrol approximately 110 patients and, if successful, could support accelerated approval for mirvetuximab. ImmunoGen initiated SORAYA in Q1 2020 and anticipates topline data in the middle of 2021, with a Biologics License Application (BLA) filing in H2 2021 and approval in 2022. Concurrent with SORAYA, ImmunoGen is enrolling a PIII confirmatory study, MIRASOL, which could support full approval of mirvetuximab. The study is evaluating mirvetuximab compared to single-agent chemotherapy in 430 patients with FRα-high platinum-resistant ovarian cancer who have received up to three prior regimens. Topline data are expected in H1 2022, with the potential for full approval in 2023 [11]
Dec 20PIII single-arm SORAYA study (NCT04296890) is recruiting in countries including the US and Europe (not UK). Collection of primary outcome data (objective response rate) is due to complete Jul 21 [10].
Dec 20PIII MIRASOL study is recruiting in countries including the US and Europe (not UK) [10].
Dec 19PIII MIRASOL study (NCT04209855) starts. It is designed to compare the efficacy and safety of mirvetuximab soravtansine vs. investigator´s choice chemotherapy in patients with platinum-resistant high-grade epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of FRα. Patients will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. Folate receptor alpha (FRα) positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay. 430 patients will be recruited (presumably in the US). Collection of primary outcome data (PFS) is due to complete Jun 22 [9].
Mar 19Top-line data from the FORWARD 1 PIII trial (NCT02631876) indicate that mirvetuximab soravtansine failed to meet its primary endpoint (extend progression free survival (PFS) by more than chemotherapy) [5]. The company has reported the key findings from the study as no improvement in PFS (HR 0.98, p=0.897) and no improvement in overall survival (HR 0.81, p=0.248), yet there was a high overall response rate (22% vs. 12% with chemotherapy, p=0.015, not a primary endpoint) [6]. In a pre-specified subgroup of patients with high expression of folate receptor (FR)-alpha (60% of the total trial population), PFS was numerically improved with mirvetuximab soravtansine compared to chemotherapy (HR 0.69, p=0.049), yet this was not statistically significant as the trial failed to meet its primary efficacy endpoint. Overall response rate and overall survival were both noted to be improved in this subgroup of patients [6]. Tolerability of mirvetuximab soravtansine was reported to be better than with chemotherapy, with fewer grade 3 or greater adverse events (46% vs. 61%), fewer dose reductions (20% vs. 31%) and fewer discontinuations due to drug-related adverse events (5% vs. 8%) [6]. Most common adverse events were nausea (54%), diarrhoea (44%) and blurred vision (43%) [6].
Mar 18Positive data from a cohort of the FORWARD 1 trial. The combination of mirvetuximab soravtansine, bevacizumab and carboplatin in pts with platinum-sensitive FRa-positive epithelial ovarian cancer was tested in 14 pts who were heavily pre-treated. In 8 pts who expressed FR-alpha at medium or high levels, the confirmed overall response rate (ORR) was 63%, with a median PFS of 8.6 months. Of 14 pts, the confirmed ORR was 43% with a median PFS of 5.2 months. In this group, the patients had already received a median of 4.5 prior lines of systemic therapy. Patients receiving the combination showed good tolerance for the drug, consistent with the safety profiles of each drug. As a result of the study results, ImmunoGen plans to test another 35 pts with medium or high FR-alpha expression levels.[3]
Jan 18ImmunoGen changed design of FORWARD I trial from PII to PIII which will support full marketing approval of mirvetuximab soravtansine. The primary endpoint of the trial will be PFS and pts will be randomised 2:1 to receive mirvetuximab soravtansine or physician´s choice of chemotherapy.[2]
Nov 17ImmunoGen announced plans to initiate a cohort in Q1 2018 to evaluate the combination of mirvetuximab soravtansine, bevacizumab and carboplatin in pts with platinum-sensitive FRa-positive epithelial ovarian cancer.[2]
Apr 16ImmunoGen added mirvetuximab soravtansine and pembrolizumab combination therapy cohort to this trial (IMGN0402; Keynote409; NCT02606305).[2]
Nov 15ImmunoGen initiated the PIb/II FORWARD II study to evaluate the safety and efficacy of mirvetuximab soravtansine in combination with bevacizumab (n = 35), carboplatin or pegylated liposomal doxorubicin, in pts with folate receptor alpha (FRa)-positive advanced epithelial ovarian cancer, primary peritoneal cancer, fallopian tube cancer, or endometrial cancer (IMGN0402; Keynote409; NCT02606305) enrolling ~ 300 pts (who were previously treated with 3-4 regimens) in the US, Canada, Europe.[2]

Evidence based evaluations