What side effects are associated with this type of intervention?

Common treatments for ovarian cancer, particularly antibody-drug conjugates (ADCs) like XMT-1536 (upifitamab rilsodotin), often cause side effects such as fatigue, nausea, anemia, and gastrointestinal issues. Targeted therapies, including PARP inhibitors like olaparib, also frequently result in nausea, fatigue, vomiting, and anemia. These side effects are typically manageable and vary in severity.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of ovarian cancer, including antibody-drug conjugates (ADCs) and PARP inhibitors. One notable ADC is mirvetuximab soravtansine, which targets the folate receptor alpha and has shown efficacy in ovarian cancer. Additionally, PARP inhibitors like olaparib, niraparib, and rucaparib have been approved for maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer, particularly those with BRCA mutations. These therapies represent significant advancements in the targeted treatment of ovarian cancer, similar to the investigational ADC XMT-1536 (upifitamab rilsodotin) targeting NaPi2b.

What other types of research exist?

Promising novel alternatives to XMT-1536 for ovarian cancer patients include: 1) Mirvetuximab soravtansine, an antibody-drug conjugate targeting folate receptor alpha, which has shown efficacy in platinum-resistant ovarian cancer. 2) PARP inhibitors like olaparib, niraparib, and rucaparib, especially for patients with BRCA mutations or homologous recombination deficiency. 3) Immunotherapies such as pembrolizumab, an anti-PD-1 antibody, which has shown promise in combination with other agents. 4) Bevacizumab, an anti-VEGF antibody, used in combination with chemotherapy for advanced ovarian cancer. These alternatives offer targeted approaches and have demonstrated potential in improving outcomes for ovarian cancer patients.

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Monoclonal Antibodies

Upifitamab Rilsodotin for Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for ovarian cancer include chemotherapy, PARP inhibitors, and antibody-drug conjugates (ADCs). Chemotherapy works by targeting rapidly dividing cells, causing cell death, but it can also affect healthy cells, leading to side effects. PARP inhibitors, such as olaparib and rucaparib, exploit the concept of synthetic lethality by targeting cancer cells with BRCA mutations, leading to DNA damage and cell death. ADCs, like XMT-1536 (upifitamab rilsodotin), combine an antibody specific to a cancer cell marker (NaPi2b) with a cytotoxic drug, delivering the drug directly to cancer cells and minimizing damage to healthy cells. These targeted therapies are crucial for ovarian cancer patients as they offer more precise treatment options, potentially improving efficacy and reducing side effects.

Phase 1 & 2

Waitlist Available

Research Sponsored by Mersana Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Platinum-resistant disease

One to 4 prior lines of systemic therapy for ovarian cancer

Must not have

Subjects not in sinus rhythm at screening with HR >45- <100

Prior history of liver disease such as liver cirrhosis, hepatic fibrosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every 8 weeks until disease progression or up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new medicine for patients with certain hard-to-treat cancers. The medicine aims to help patients whose cancers do not respond to standard treatments.

Who is the study for?

This trial is for adults with platinum-resistant ovarian cancer or non-small cell lung cancer who have measurable disease and are in good physical condition (ECOG 0 or 1). They must have adequate organ function, no severe heart rhythm problems, and not be on certain medications that affect liver enzymes. Pregnant women, those with untreated brain metastases, active infections like HIV or hepatitis B/C, severe diseases that could interfere with the study, a history of other cancers within 2 years (with some exceptions), or recent major surgery cannot participate.

What is being tested?

The trial tests upifitamab rilsodotin (XMT-1536), an antibody-drug conjugate given intravenously every four weeks to patients whose tumors likely express NaPi2b. It includes dose escalation for safety assessment and expansion segments specifically for patients with platinum-resistant ovarian cancer and adenocarcinoma subtype of non-small cell lung cancer.

What are the potential side effects?

Potential side effects include reactions related to the infusion process itself as well as possible impacts on various organs due to the drug's mechanism of action. Specific side effects aren't listed but would typically relate to how this type of drug affects cells.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition did not improve with platinum-based chemotherapy.

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I have had 1 to 4 treatments for ovarian cancer.

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I have high-grade serous ovarian, fallopian tube, or peritoneal cancer that has spread or come back.

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I have had bevacizumab as part of my first or second line of treatment.

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I am fully active or can carry out light work.

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My blood tests and kidney function are within normal ranges, and I can make my own medical decisions.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart rate is between 45 and 100, and I don't have a normal heart rhythm.

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I have a history of liver disease.

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I do not have any severe illnesses that could affect my trial participation.

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I have had lung inflammation or scarring.

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I am not taking medication that strongly affects liver enzyme activity.

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I have a heart valve problem that is more than moderate.

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My cancer did not respond to platinum-based chemotherapy.

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I am taking medication that strongly affects liver enzyme levels and cannot stop while on the study treatment.

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I have previously been treated with a drug similar to mirvetuximab soravtansine.

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I have brain metastases that haven't been treated or a history of cancer spreading to my brain's lining.

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I haven't had major surgery or cancer treatment recently.

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I do not have an active infection with HIV, hepatitis B, or hepatitis C.

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I use oxygen therapy regularly.

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My heart does not have uncontrolled irregular rhythms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 weeks after first response and every 8 weeks until disease progression or up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 weeks after first response and every 8 weeks until disease progression or up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 weeks after first response and every 8 weeks until disease progression or up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

DES and EXP: Safety and Tolerability

DES: Maximum tolerated dose or recommended Phase 2 dose

EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin)

+2 more

Secondary study objectives

DES and EXP: Anti-drug antibody and neutralizing antibody

DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin)

DES and EXP: Maximum concentration of XMT-1536 (upifitamab rilsodotin)

+8 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: QTc Sub-StudyExperimental Treatment1 Intervention

For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536. This cohort is closed to enrollment.

Group II: Pivotal Cohort (UPLIFT)Experimental Treatment1 Intervention

Patients with platinum-resistant ovarian cancer will receive XMT-1536 (upifitamab rilsodotin) to further confirm the efficacy. This cohort is closed to enrollment.

Group III: Dose Expansion - Ovarian CancerExperimental Treatment1 Intervention

Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose. This cohort is closed to enrollment.

Group IV: Dose Expansion - NSCLC adenocarcinomaExperimental Treatment1 Intervention

Group V: Dose EscalationExperimental Treatment1 Intervention

XMT-1536 (upifitamab rilsodotin) treatment is administered in groups of patients who will receive doses that increase over time. This cohort is closed to enrollment.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

upifitamab rilsodotin

2017

Completed Phase 1

~210

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for ovarian cancer include chemotherapy, PARP inhibitors, and antibody-drug conjugates (ADCs). Chemotherapy works by targeting rapidly dividing cells, causing cell death, but it can also affect healthy cells, leading to side effects. PARP inhibitors, such as olaparib and rucaparib, exploit the concept of synthetic lethality by targeting cancer cells with BRCA mutations, leading to DNA damage and cell death. ADCs, like XMT-1536 (upifitamab rilsodotin), combine an antibody specific to a cancer cell marker (NaPi2b) with a cytotoxic drug, delivering the drug directly to cancer cells and minimizing damage to healthy cells. These targeted therapies are crucial for ovarian cancer patients as they offer more precise treatment options, potentially improving efficacy and reducing side effects.

Integrating Precision Medicine into the Contemporary Management of Gynecologic Cancers.