Mirvetuximab + Olaparib for Ovarian Cancer

Overseen By Samantha Hopp

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Ocular 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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

53 Participants Needed

Trial Summary

What is the purpose of this trial?

The Principal Investigator hypothesizes the combination of MIRV and Olaparib is an effective, and tolerable, maintenance therapy strategy in platinum sensitive recurrent ovarian cancer.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for specific drugs. If you are taking strong or moderate CYP3A inhibitors, you need to stop them 2 weeks before starting the study treatment. If you are on strong or moderate CYP3A inducers, the washout period is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.

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

Research shows that Mirvetuximab Soravtansine has shown promising results in treating ovarian cancer, especially in patients who are resistant to platinum-based treatments. Olaparib is effective as a maintenance therapy for ovarian cancer that responds to platinum-based chemotherapy, even in patients without specific genetic mutations. ^{1 2 3 4 5}

What safety information is available for Mirvetuximab Soravtansine and Olaparib in treating ovarian cancer?

Mirvetuximab Soravtansine (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 treating ovarian cancer. ^{1 3 4 6 7}

How is the drug combination of Mirvetuximab and Olaparib unique for treating ovarian cancer?

The combination of Mirvetuximab and Olaparib is unique because it targets ovarian cancer with high folate receptor alpha expression and BRCA mutations, using Mirvetuximab's antibody-drug conjugate to deliver a toxic agent directly to cancer cells, while Olaparib inhibits DNA repair in cancer cells, potentially enhancing treatment effectiveness. ^{1 6 8 9 10}

Research Team

Bradley R. Corr

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for women over 18 with high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer that responded to platinum therapy. They must have completed 4-8 cycles of chemotherapy and not be pregnant or breastfeeding. Participants need normal organ function and can't join if they've had certain severe reactions to previous treatments, are taking drugs that interact poorly with the study medication, or have specific health conditions.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Provision to sign and date the consent form

My kidney function, measured by creatinine clearance, is good.

Exclusion Criteria

Women who are pregnant or breastfeeding, and who do not agree to use a highly effective contraceptive method(s) while on study drug and for at least 3 months after the last dose of MIRV

I have untreated or symptomatic brain metastases.

I am not taking strong or moderate CYP3A inhibitors.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead In

Initial phase to assess safety of the treatment combination

3 weeks

1 visit (in-person)

Treatment

Participants receive MIRV and Olaparib until progression, unacceptable toxicity, withdrawal, or death

12 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Mirvetuximab Soravtansine
• Olaparib

Trial Overview The trial tests a combination of Mirvetuximab Soravtansine (MIRV) and Olaparib as maintenance therapy in patients with recurrent ovarian cancer who previously responded well to platinum-based chemotherapy. The hypothesis suggests this combo could be effective and tolerable for keeping the cancer at bay after initial treatment success.

Participant Groups

Group I: Treatment Experimental Treatment 2 Interventions

All patients will receive MIRV at 5mg/kg AIBW administered through IV infusion on Day 1 of every 3-week cycle (Q3W). All patients will receive Olaparib at 300mg taken orally twice daily with or without food. Dosage and administration will follow current single-agent Olaparib package insert dosage and administration guidelines. Patients will continue to receive MIRV and Olaparib until PD, unacceptable toxicity, withdrawal of consent, or death, whichever comes first. If toxicity deems the patient to discontinue one drug, the patient may continue the other drug until PD, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.

Group II: Safety Lead In Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

ImmunoGen, Inc.

Industry Sponsor

Trials

33

Recruited

4,000+

Findings from Research

Mirvetuximab soravtansine (MIRV) demonstrated a 34.2% objective response rate and a progression-free survival of 5.82 months in 605 patients with advanced or recurrent ovarian cancer, indicating its efficacy as a second-line treatment.

The overall incidence of adverse events (AEs) was 87.4%, with 27.1% experiencing grade ≥3 AEs, primarily including vision blurring, nausea, and diarrhea, suggesting that while MIRV is effective, it does come with a notable risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and toxicity of mirvetuximab soravtansine, a novel antibody-drug conjugate, in the treatment of advanced or recurrent ovarian cancer: a meta-analysis. Xu, K., Wang, T., Pan, S., et al.[2023]

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

Mirvetuximab soravtansine is a promising antibody-drug conjugate that targets folate receptor-α, showing favorable tolerability and encouraging efficacy, particularly in patients with platinum-resistant ovarian cancer.

Ongoing Phase III and Phase Ib/II trials are currently assessing its effectiveness as a monotherapy and in combination treatments, which will clarify its potential role in treating advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer. Moore, KN., Martin, LP., O'Malley, DM., et al.[2019]

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]

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]

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]

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]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

References

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

The efficacy and toxicity of mirvetuximab soravtansine, a novel antibody-drug conjugate, in the treatment of advanced or recurrent ovarian cancer: a meta-analysis. [2023]

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

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

3. England pubmed.ncbi.nlm.nih.gov

A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer. [2019]

4. 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]

5. 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]

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

New Drug Treats Female Reproductive Cancers. [2023]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]