Carboplatin + Mirvetuximab for Ovarian Cancer

Overseen By Rebecca Arend, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: IV antibiotics

Disqualifiers: Corneal disorders, Cardiac 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 21 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study design is a single arm Phase II trial to document the feasibility of carboplatin-mirvetuximab - in patients with advanced-stage EOC. Patients with biopsy confirmed, newly diagnosed, advanced-stage serous EOC deemed appropriate for NACT will have their tumors evaluated for FRα receptor over-expression via a centralized immunohistochemical assay (IHC) and identified as appropriate for study participation if IHC staining is PS2+ in \>75% of cells (40% of all serous patients). Eligible patients will receive NACT with one cycle of carboplatin, followed by mirvetuximab + carboplatin (if FRα +) every 21 days for three cycles prior to interval cytoreductive surgery (iCRS). A total of 70 will be included in the study. Following completion of 4 cycles total of NACT and after allowing for appropriate recovery of cycle # 4, patients eligible for surgery, will undergo an iCRS. Patients will then complete 3 more cycles of mirvetuximab + carboplatin for a total of 7 intended cycles of treatment. It is up to the treating physician if they want to add bevacizumab to the last 2 cycles or use any type of maintenance therapy. The decision to add bevacizumab or use maintenance therapy does not need to be made upfront. Patients will sign a screening consent form prior to tissue biopsy. If a patient is found to be FRα negative, their treating physician can select the treatment they deem appropriate and the patient will be declared a screen failure. Patients with BRCA mutations are not excluded from this trial and are allowed to receive standard of care maintenance therapy including bevacizumab and/or PARP inhibitors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What data supports the effectiveness of the drug Mirvetuximab Soravtansine for ovarian cancer?

Mirvetuximab Soravtansine has shown effectiveness in treating ovarian cancer, particularly in patients with high folate receptor alpha (FRα) expression. In a trial, it achieved a 32.4% response rate in patients with platinum-resistant ovarian cancer, and when combined with bevacizumab, it showed a 64% response rate in patients with recurrent ovarian cancer. ^{1 2 3 4 5}

What safety information is available for the treatment Carboplatin + Mirvetuximab for Ovarian Cancer?

Mirvetuximab soravtansine, also known as Elahere, has been associated with risks of eye problems, lung inflammation, nerve damage, and potential harm to unborn babies. These safety concerns are important to consider when evaluating its use in combination with carboplatin for ovarian cancer. ^{1 2 4 5 6}

What makes the drug Mirvetuximab Soravtansine unique for ovarian cancer treatment?

Mirvetuximab Soravtansine is unique because it is an antibody-drug conjugate (ADC) that specifically targets folate receptor alpha (FRα), which is often overexpressed in ovarian cancer cells, delivering a potent cancer-killing agent directly to the tumor. This targeted approach can lead to better outcomes for patients with high FRα expression, especially those with platinum-resistant ovarian cancer. ^{1 2 3 5 7}

Research Team

Rebecca C. Arend

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for women with advanced-stage ovarian, fallopian tube, or primary peritoneal cancer who haven't had previous systemic anti-cancer therapy. They must have high-grade serous epithelial ovarian cancer that's positive for FRα expression and be fit enough to undergo chemotherapy and surgery. Women of childbearing potential must use effective contraception and not be pregnant or breastfeeding.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

My tumor is mostly positive for a specific protein marker.

Women of childbearing potential must have a negative pregnancy test within 4 days before starting the study drug.

Exclusion Criteria

I have had hepatitis B or C in the past.

I have previously been treated with MIRV or drugs targeting FRα.

I have a history of MS, another demyelinating disease, or Lambert-Eaton syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive neoadjuvant chemotherapy with carboplatin and mirvetuximab soravtansine for 7 cycles, with the first cycle being carboplatin alone and subsequent cycles including mirvetuximab

21 weeks

7 visits (in-person, every 21 days)

Interval Cytoreductive Surgery (iCRS)

Eligible patients undergo interval cytoreductive surgery after completion of neoadjuvant chemotherapy

3-4 weeks for recovery

1 visit (in-person)

Post-Surgery Treatment

Participants complete 3 more cycles of mirvetuximab and carboplatin, with optional addition of bevacizumab

9 weeks

3 visits (in-person, every 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with radiographic assessments and survival follow-up

2 years

Every 3 months (in-person or virtual)

Treatment Details

Interventions

• Mirvetuximab Soravtansine

Trial Overview The study tests a combination of Carboplatin with Mirvetuximab Soravtansine (MIRV) in patients whose tumors over-express the FRα receptor. Participants will receive this treatment every three weeks before surgery, followed by additional cycles after surgery. The option to add Bevacizumab or maintenance therapy later on is at the physician's discretion.

Participant Groups

Group I: Arm A: alpha receptor positive_neoadjuvant chemotherapy regimen Experimental Treatment 1 Intervention

* IV Carboplatin AUC 5 (Q21 days) 7 cycles (first cycle is Carbo alone, dosing for C1D1 will be provider's choice) * IV Mirvetuximab 6 mg/kg (adjusted ideal body weight) day 1 (Q21 days) 6 cycles (starting with cycle #2)

Group II: Arm B: alpha receptor negative Active Control 1 Intervention

If a patient is found to be negative for FRα expression, they will be ineligible to receive the study treatment under the main study (Arm A). FRα negative patients will be enrolled under the biomarker-only arm (Arm B), and their treating physician can select the treatment they deem appropriate.

Mirvetuximab Soravtansine is already approved in United States for the following indications:

Approved in United States as Elahere for:

• Platinum-resistant epithelial ovarian cancer
• Fallopian tube cancer
• Primary peritoneal cancer

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

In a study involving 18 patients with recurrent ovarian cancer, the combination of mirvetuximab soravtansine and carboplatin showed a high objective response rate of 71%, indicating significant antitumor activity.

The treatment was generally well-tolerated, with most adverse events being mild, suggesting a favorable safety profile for this combination therapy in patients with platinum-sensitive ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer. Moore, KN., O'Malley, DM., Vergote, I., et al.[2019]

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]

The combination of mirvetuximab soravtansine and bevacizumab shows promising efficacy in treating women with recurrent ovarian cancer that has high folate receptor alpha (FRα) expression, achieving a 64% objective response rate.

Patients treated with this combination therapy experienced a median progression-free survival of 10.6 months, indicating a significant benefit regardless of their platinum sensitivity status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Significant Activity" for ADC in Ovarian Cancer. [2022]

The combination of mirvetuximab soravtansine and bevacizumab showed significant antitumor activity in patients with platinum-resistant ovarian cancer, achieving an objective response rate of 44% among 94 patients, with a median duration of response of 9.7 months.

The treatment was well-tolerated, with common side effects like blurred vision, diarrhea, and nausea being mostly mild, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gilbert, L., Oaknin, A., Matulonis, UA., et al.[2023]

Mirvetuximab soravtansine-gynx (Elahere) has received accelerated approval for treating adult patients with folate receptor α-positive, platinum-resistant ovarian cancer after one to three prior treatments, indicating its efficacy in a challenging patient population.

The drug carries significant safety warnings, including risks of ocular toxicity, pneumonitis, peripheral neuropathy, and embryo-fetal toxicity, which are important considerations for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Treats Female Reproductive Cancers. Aschenbrenner, DS.[2023]

Mirvetuximab soravtansine-gynx received accelerated FDA approval for treating FRα-positive, platinum-resistant ovarian cancer, showing an overall response rate of 31.7% in a study of 104 patients, with a median response duration of 6.9 months.

The treatment carries significant safety warnings, including risks of severe ocular toxicity, pneumonitis, and peripheral neuropathy, highlighting the importance of monitoring for these adverse effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRα-Positive, Platinum-Resistant Ovarian Cancer. Dilawari, A., Shah, M., Ison, G., et al.[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]

References

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

Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer. [2019]

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

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

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

"Significant Activity" for ADC in Ovarian Cancer. [2022]

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

Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. [2023]

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

New Drug Treats Female Reproductive Cancers. [2023]

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

FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRα-Positive, Platinum-Resistant Ovarian Cancer. [2023]

7. 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]