IMGN853 for Endometrial Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Alessandro Santin
Must not be taking: Folate supplements
Disqualifiers: Cardiac disease, Stroke, Liver disease, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the activity and safety profile of mirvetuximab soravtansine (IMGN853) in patients with type II endometrial cancers that overexpress folate receptor alpha (FRα).
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, there is a requirement for a 'washout period' (time without taking certain medications) from prior systemic anti-neoplastic therapy, which is either five half-lives or four weeks, whichever is shorter.
What data supports the effectiveness of the drug Mirvetuximab Soravtansine (IMGN853) for endometrial cancer?
Research shows that Mirvetuximab Soravtansine is effective in treating aggressive endometrial cancers that overexpress the folate receptor alpha (FRα). In studies, it led to complete tumor resolution in certain endometrial cancer models and increased survival in uterine cancer models with high FRα expression.
12345What safety data exists for Mirvetuximab Soravtansine (IMGN853) in humans?
Mirvetuximab Soravtansine has been associated with low-grade eye and stomach-related side effects, which are generally mild and reversible. These side effects were observed in studies involving patients with ovarian cancer.
12467What makes the drug IMGN853 unique for treating endometrial cancer?
IMGN853 (Mirvetuximab Soravtansine) is unique because it specifically targets the folate receptor alpha (FRα), which is overexpressed in certain aggressive endometrial cancers. This targeted approach allows the drug to deliver a potent cancer-killing agent directly to the cancer cells, potentially improving outcomes for patients with FRα-positive tumors.
14589Eligibility Criteria
This trial is for women with certain types of advanced endometrial cancer that have a protein called FRα. They must have tried ≤3 treatments, not be pregnant, agree to contraception, and can't have had certain heart issues, brain conditions or other serious health problems.Inclusion Criteria
Have signed the informed consent form, and willing to adhere to the study visit schedule and other protocol requirements
My tumor is FRα-positive.
Women of child bearing potential (WCBP), must agree to use effective contraceptive methods during study treatment and for at least twelve weeks after the last dose of IMGN853
+12 more
Exclusion Criteria
I have an ongoing eye condition affecting my cornea.
I do not have any serious illnesses or active infections.
I do not have serious heart or blood vessel problems.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive IMGN853 at a dose of 6 mg/kg administered intravenously once every 3 weeks until unacceptable toxicity or disease progression
Variable, based on individual response
Every 3 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Participant Groups
The study tests the effectiveness and safety of a drug named Mirvetuximab Soravtansine (IMGN853) in patients with type II endometrial cancers overexpressing folate receptor alpha. It's for those who've had previous treatments but still show signs of cancer.
1Treatment groups
Experimental Treatment
Group I: IMGN853Experimental Treatment1 Intervention
IMGN853 administered 6 mg/kg adjusted ideal body weight (AIBW) once every three weeks (Q3W)
Mirvetuximab Soravtansine (IMGN853) is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Elahere for:
- Platinum-resistant epithelial ovarian cancer
- Fallopian tube cancer
- Primary peritoneal cancer
🇪🇺 Approved in European Union as Elahere for:
- Epithelial ovarian cancer
- Fallopian tube cancer
- Primary peritoneal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Smilow Cancer Hospital at Yale New HavenNew Haven, CT
Loading ...
Who Is Running the Clinical Trial?
Alessandro SantinLead Sponsor
ImmunoGen, Inc.Industry Sponsor
References
Mirvetuximab soravtansine for platinum-resistant epithelial ovarian cancer. [2023]Mirvetuximab soravtansine (mirvetuximab) is an antibody drug conjugate (ADC) comprised of a humanized folate receptor alpha (FRα)-binding monoclonal antibody attached via a cleavable linker to the cytotoxic maytansinoid molecule, DM4. FRα is expressed in several epithelial cancers, including high grade serous ovarian cancer (HGSOC). Mirvetuximab received accelerated approval by the United States Food and Drug Administration (FDA) in November 2022 based on the results of the SORAYA trial, which tested mirvetuximab for the treatment of patients with recurrent platinum resistant HGSOC with high FRα expression and showed an overall response rate (ORR) of 32.4% and a median duration of response of 6.9 months. Mirvetuximab toxicities included low grade ocular and gastrointestinal toxicities. The National Comprehensive Cancer Network (NCCN) ovarian cancer 2023 guidelines adopted mirvetuximab as 2A, and mirvetuximab combined with bevacizumab as 2B, recommendations.
Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. [2021]Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).
Mirvetuximab Soravtansine in Platinum-Resistant Ovarian Cancer. [2023]Ovarian cancer is the second leading cause of death from gynecologic malignancies worldwide. Management of platinum-resistant disease is challenging and clinical outcomes with standard chemotherapy are poor. Over the past decades, significant efforts have been made to understand drug resistance and develop strategies to overcome treatment failure. Antibody drug conjugates (ADCs) are a rapidly growing class of oncologic therapeutics, which combine the ability to target tumor-specific antigens with the cytotoxic effects of chemotherapy. Mirvetuximab soravtansine is an ADC comprising an IgG1 monoclonal antibody against the folate receptor alpha (FRα) conjugated to the cytotoxic maytansinoid effector molecule DM4 that has shown promising clinical activity in patients with FR-α-positive ovarian cancer. This review summarizes current evidence of mirvetuximab soravtansine in platinum-resistant ovarian cancer, focusing on clinical activity, toxicity, and future directions.
Mirvetuximab Soravtansine: First Approval. [2023]Mirvetuximab soravtansine (mirvetuximab soravtansine-gynx; Elahere™) is an antibody-drug conjugate (ADC), which is comprised of a folate receptor α (FRα) directed antibody conjugated to a microtubule inhibitor via a cleavable linker. The ADC is being developed by ImmunoGen for the treatment of FRα expressing cancers. In November 2022, mirvetuximab soravtansine was approved in the USA for the treatment of adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens. This article summarizes the milestones in the development of mirvetuximab soravtansine leading to this first approval.
In Vitro and In Vivo Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers. [2020]Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. The in vitro cytotoxic activity and bystander effect were studied in primary uterine cancer cell lines expressing differential levels of FRα. In vivo antitumor efficacy of IMGN853 was evaluated in xenograft/patient-derived xenograft (PDX) models. Semiquantitative IHC analysis indicated that 41% of the USC patients overexpress FRα. Further, overexpression of FRα (i.e., 2+) was detected via flow cytometry in 22% (2/9) of primary endometrioid and in 27% (3/11) of primary USC cell lines. Increased cytotoxicity was seen with IMGN853 treatment compared with control in 2+ expressing uterine tumor cell lines. In contrast, tumor cell lines with low FRα showed no difference when exposed to IMGN853 versus control. IMGN853 induced bystander killing of FRα = 0 tumor cells. In an endometrioid xenograft model (END(K)265), harboring 2+ FRα, IMGN853 treatment showed complete resolution of tumors (P < 0.001). Treatment with IMGN853 in the USC PDX model (BIO(K)1), expressing 2+ FRα, induced twofold increase in median survival (P < 0.001). IMGN853 shows impressive antitumor activity in biologically aggressive FRα 2+ uterine cancers. These preclinical data suggest that patients with chemotherapy resistant/recurrent endometrial cancer overexpressing FRα may benefit from this treatment. Mol Cancer Ther; 17(5); 1003-11. ©2018 AACR.
Evaluation of Prophylactic Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the Antibody-Drug Conjugate Mirvetuximab Soravtansine. [2020]Reversible, low-grade ocular adverse events (AE) are associated with administration of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeted antibody-drug conjugate undergoing phase III clinical evaluation in platinum-resistant ovarian cancer. This study investigated the underlying mechanisms of ocular toxicity and evaluated primary prophylactic use of corticosteroid eye drops in patients receiving mirvetuximab soravtansine.
Population pharmacokinetics of mirvetuximab soravtansine in patients with folate receptor-α positive ovarian cancer: The antibody-drug conjugate, payload and metabolite. [2023]Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate recently approved for the treatment of folate receptor-α positive ovarian cancer. The aim of this study was to develop a population pharmacokinetic model to describe the concentration-time profiles of mirvetuximab soravtansine, the payload (DM4) and a metabolite (S-methyl-DM4).
Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors. [2019]Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors.
Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study. [2019]Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.