IMGN853 for Endometrial Cancer

Overseen By Alessandro Santin

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Alessandro Santin

Must not be taking: Folate supplements

Disqualifiers: Cardiac disease, Stroke, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Variable, based on individual response

50 Participants Needed

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. ^{1 2 3 4 5}

What 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. ^{1 2 4 6 7}

What 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. ^{1 4 5 8 9}

Research Team

Alessandro Santin

Principal Investigator

Yale University

Eligibility 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

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.

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

Treatment Details

Interventions

• Mirvetuximab Soravtansine (IMGN853)

Trial Overview 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.

Participant Groups

Group I: IMGN853 Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Alessandro Santin

Lead Sponsor

Trials

4

Recruited

140+

ImmunoGen, Inc.

Industry Sponsor

Trials

33

Recruited

4,000+

Findings from Research

Mirvetuximab soravtansine is an antibody-drug conjugate that received FDA accelerated approval for treating recurrent platinum-resistant high-grade serous ovarian cancer (HGSOC), showing an overall response rate of 32.4% and a median duration of response of 6.9 months in the SORAYA trial.

The treatment has a favorable safety profile, with primarily low-grade ocular and gastrointestinal toxicities, making it a promising option for patients with high FRα expression in their tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirvetuximab soravtansine for platinum-resistant epithelial ovarian cancer. Porter, RL., Matulonis, UA.[2023]

In a phase III study involving 366 patients with platinum-resistant epithelial ovarian cancer, mirvetuximab soravtansine (MIRV) did not significantly improve progression-free survival compared to standard chemotherapy, but showed better outcomes in secondary measures for patients with high folate receptor alpha (FRα) expression.

MIRV demonstrated a more favorable safety profile, with fewer severe treatment-related adverse events and lower rates of dose reductions and treatment discontinuations compared to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Moore, KN., Oza, AM., Colombo, N., et al.[2021]

Mirvetuximab soravtansine, an antibody-drug conjugate targeting the folate receptor alpha, has shown promising clinical activity in treating platinum-resistant ovarian cancer, which is known for poor outcomes with standard chemotherapy.

This treatment combines a targeted approach with the cytotoxic effects of a chemotherapy agent, potentially offering a new strategy to overcome drug resistance in ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirvetuximab Soravtansine in Platinum-Resistant Ovarian Cancer. Gonzalez-Ochoa, E., Veneziani, AC., Oza, AM.[2023]

Mirvetuximab soravtansine is an antibody-drug conjugate specifically designed to target folate receptor α (FRα) in cancers, combining an antibody with a microtubule inhibitor for effective treatment.

In November 2022, it received FDA approval for treating adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer after 1-3 prior treatments, highlighting its efficacy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mirvetuximab Soravtansine: First Approval. Heo, YA.[2023]

In a study of 90 endometrioid and uterine serous carcinoma samples, 41% of patients showed overexpression of the folic acid receptor alpha (FRα), indicating it as a potential target for treatment with IMGN853 (mirvetuximab soravtansine).

Preclinical results demonstrated that IMGN853 significantly improved tumor resolution and increased median survival in xenograft models of endometrial cancer with high FRα expression, suggesting it could be an effective option for patients with chemotherapy-resistant or recurrent endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers. Altwerger, G., Bonazzoli, E., Bellone, S., et al.[2020]

Mirvetuximab soravtansine, an antibody-drug conjugate for treating platinum-resistant ovarian cancer, can cause reversible low-grade ocular side effects, such as blurred vision and keratopathy, in about 40% of patients, but no severe ocular events were reported.

Using corticosteroid eye drops as a preventive measure during treatment led to fewer dose reductions and no discontinuations due to ocular adverse events, suggesting that this approach may help manage the ocular toxicity associated with mirvetuximab soravtansine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Prophylactic Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the Antibody-Drug Conjugate Mirvetuximab Soravtansine. Matulonis, UA., Birrer, MJ., O'Malley, DM., et al.[2020]

Mirvetuximab soravtansine, a new treatment for folate receptor-α positive ovarian cancer, was studied in 543 patients, showing that it can be administered safely at a standard dose of 6 mg/kg without needing adjustments for most patients, including those with mild to moderate renal or hepatic impairment.

The pharmacokinetic model developed in this study indicates that factors like body weight, serum albumin, and age do not necessitate dose adjustments, ensuring consistent efficacy and safety across diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of mirvetuximab soravtansine in patients with folate receptor-α positive ovarian cancer: The antibody-drug conjugate, payload and metabolite. Tu, YP., Hanze, E., Zhu, F., et al.[2023]

In a phase 1 study involving 44 patients with FRα-positive solid tumors, mirvetuximab soravtansine (IMGN853) showed a manageable safety profile, with most side effects being mild (grade 1 or 2) such as fatigue and blurred vision.

The study found encouraging preliminary clinical activity, particularly in patients with ovarian cancer, with a recommended phase 2 dose established at 6.0 mg/kg every three weeks, and two patients achieving partial tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors. Moore, KN., Borghaei, H., O'Malley, DM., et al.[2019]

Mirvetuximab soravtansine (IMGN853) demonstrated a manageable safety profile in patients with platinum-resistant ovarian cancer, with most adverse events being mild and primarily consisting of diarrhea, blurred vision, nausea, and fatigue.

The treatment showed clinical activity, with a confirmed objective response rate of 26% overall, and a higher response rate of 39% in patients who had received three or fewer prior lines of therapy, indicating potential effectiveness in earlier treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Moore, KN., Martin, LP., O'Malley, DM., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Mirvetuximab soravtansine for platinum-resistant epithelial ovarian cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Mirvetuximab Soravtansine in Platinum-Resistant Ovarian Cancer. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Mirvetuximab Soravtansine: First Approval. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

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]

6. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Prophylactic Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the Antibody-Drug Conjugate Mirvetuximab Soravtansine. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of mirvetuximab soravtansine in patients with folate receptor-α positive ovarian cancer: The antibody-drug conjugate, payload and metabolite. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

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]