Carboplatin + Mirvetuximab for Ovarian Cancer

Recruiting at 8 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for advanced ovarian cancer, specifically examining the effectiveness of carboplatin and mirvetuximab (also known as Elahere or Mirvetuximab soravtansine-gynx) together. The focus is on patients whose tumors exhibit high levels of a specific protein, FRα, which aids cancer growth. Those with advanced-stage serous ovarian cancer and FRα-positive tumors might be suitable candidates. Participants will receive a combination of chemotherapy and the new drug, followed by surgery, to assess the approach's effectiveness. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that mirvetuximab soravtansine is generally well-tolerated by patients with ovarian cancer. Studies indicate it has a manageable safety profile, even for those who have undergone many treatments. Most side effects, such as tiredness, nausea, or vision changes, are manageable, and serious issues are rare.

Carboplatin, a common cancer treatment, is also part of the study. It is effective but can cause side effects like low blood counts and hair loss. Doctors closely monitor these expected effects.

Overall, previous studies suggest that the treatment combination in this trial appears safe. Patients should always consult their doctor about any concerns for personalized advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about Mirvetuximab Soravtansine for ovarian cancer because it targets the folate receptor alpha (FRα) on cancer cells, which is not typically addressed by standard chemotherapy. Most treatments for ovarian cancer involve drugs like Paclitaxel and Carboplatin, which attack dividing cells but don't specifically target cancer cell markers. Mirvetuximab Soravtansine uses an antibody-drug conjugate approach, where an antibody specifically binds to FRα, delivering a potent anti-cancer agent directly to the tumor cells. This precision could potentially lead to more effective treatment with fewer side effects compared to conventional chemotherapy.

What evidence suggests that carboplatin and mirvetuximab could be effective for ovarian cancer?

Research has shown that combining mirvetuximab soravtansine with carboplatin may offer promise for treating ovarian cancer. In this trial, participants with FRα-positive ovarian cancer will receive this combination treatment. Studies have found that mirvetuximab soravtansine helps patients with FRα-positive, platinum-resistant ovarian cancer live longer compared to those receiving standard chemotherapy. Specifically, a previous study revealed that about 26% of patients experienced tumor shrinkage, indicating the treatment could be effective for those with advanced ovarian cancer, especially when their tumors have the FRα receptor. ^{3 5 6 7 8}

Who Is on the Research Team?

Rebecca C. Arend

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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-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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11921575/

Mirvetuximab soravtansine: current and future applications In platinum-resistant ovarian cancer, the Phase I study (NCT01609556) demonstrated a 26.1% objective response rate and a median progression-free ...

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/fda-elahere-platinum-resistant-ovarian-cancer

Mirvetuximab Soravtansine-Gynx Approved for Ovarian ... Results showed that people with FR-α-positive, platinum-resistant ovarian tumors who were treated with Elahere lived longer overall than people ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825825008893

Safety and efficacy of mirvetuximab soravtansine, a folate ... Patients with epithelial ovarian cancer (EOC) have poor outcomes; most tumors will relapse within several years and develop resistance to platinum-based therapy ...

4. elaherehcp.com elaherehcp.com/efficacy/confirmatory-study-data

ELAHERE® efficacy and success rate for FRα positive ovarian ... Phase 3 MIRASOL trial: updated overall survival results of mirvetuximab soravtansine (MIRV) versus investigator's choice (IC) chemotherapy in patients (pts) ...

5. international-journal-of-gynecological-cancer.com international-journal-of-gynecological-cancer.com/article/S1048-891X(25)01136-3/fulltext

Mirvetuximab soravtansine in the ovarian cancer treatment ... The MIRASOL trial demonstrated that mirvetuximab significantly improves progression-free and overall survival compared to standard chemotherapy, with ocular ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40700855/

Safety and efficacy of mirvetuximab soravtansine, a folate ... Conclusions: MIRV plus pembrolizumab demonstrated anti-cancer efficacy and a tolerable safety profile in heavily pretreated patients with PROC.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309169

Mirvetuximab Soravtansine in FRα-Positive, Platinum- ... Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with ...

8. onclive.com onclive.com/view/final-piccolo-data-underscore-mirvetuximab-soravtansine-s-efficacy-in-later-line-fr-platinum-sensitive-ovarian-cancer

Final PICCOLO Data Underscore Mirvetuximab ... Mirvetuximab soravtansine continues to show efficacy and safety in final analysis of the phase 2 PICCOLO study.