What is the mechanism of action of this treatment?

Common treatments for ovarian cancer, such as adoptive cell therapy and immune checkpoint inhibitors, work by enhancing the body's immune response against cancer cells. Adoptive cell therapy, like ADP A2M4CD8, involves engineering T-cells to target specific cancer antigens, such as MAGE-A4, thereby improving the immune system's ability to attack the cancer. Nivolumab, a PD-1 inhibitor, blocks the PD-1 pathway that cancer cells use to evade immune detection, reactivating T-cells to recognize and destroy cancer cells. These targeted therapies are significant for ovarian cancer patients as they offer more precise and potentially more effective treatment options compared to traditional methods.

What side effects are associated with this type of intervention?

Common treatments for ovarian cancer, such as adoptive cell therapy (e.g., ADP A2M4CD8) and PD-1 inhibitors (e.g., Nivolumab), have notable side effects. Adoptive cell therapy can cause cytokine release syndrome (CRS) with symptoms like fever, fatigue, and muscle pain, as well as neurotoxicity, which may present as confusion or seizures. Nivolumab often leads to immune-related adverse events, including fatigue, rash, diarrhea, and endocrinopathies like hypothyroidism. Severe side effects can include pneumonitis, colitis, hepatitis, and nephritis. Both treatments necessitate careful monitoring and management of these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for ovarian cancer, including chemotherapies, targeted therapies, and immunotherapies. While adoptive cell therapies like ADP A2M4CD8 targeting MAGE-A4 are still under investigation, PD-1 inhibitors such as Nivolumab have shown promise in various cancers, including ovarian cancer. Nivolumab, a PD-1 inhibitor, works by enhancing the immune system's ability to fight cancer cells. Other immunotherapies, such as Pembrolizumab (another PD-1 inhibitor), have also been explored for ovarian cancer treatment. These therapies represent a shift towards leveraging the body's immune system to combat cancer more effectively.

What other types of research exist?

Promising alternatives for ovarian cancer treatment in 2024 include: 1) Pembrolizumab (another PD-1 inhibitor) which has shown efficacy in various cancers and is being explored in ovarian cancer. 2) Atezolizumab (PD-L1 inhibitor) which is being tested in combination with other agents for ovarian cancer. 3) PARP inhibitors like Olaparib and Niraparib, especially for patients with BRCA mutations or homologous recombination deficiency. 4) Bevacizumab (anti-VEGF) in combination with chemotherapy, which has been effective in prolonging progression-free survival. These alternatives offer different mechanisms of action and may be suitable based on individual patient profiles.

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CAR T-cell Therapy

ADP-A2M4CD8 + Nivolumab for Ovarian Cancer

Phase 2

Recruiting

Research Sponsored by Adaptimmune

Eligibility Criteria Checklist

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

Must have

Subjects will be assessed for eligibility prior to leukapheresis AND prior to lymphodepleting chemotherapy (unless otherwise noted) and must meet all specified criteria for study participation.

The initial therapy must have included at least 3 cycles of a prior platinum and taxane based chemotherapy regimen for primary disease, possibly including intraperitoneal therapy, consolidation, or extended therapy (maintenance/consolidation).

Must not have

Requirement for oxygen support (due to cardiac or pulmonary disease)

Known family history or congenital history of prolonged QT syndrome or history of torsade de pointes

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3.6 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a treatment using modified immune cells alone or with an immune-boosting drug in patients with recurrent ovarian cancer who have a specific genetic marker. The treatment aims to help the immune system better identify and destroy cancer cells.

Who is the study for?

This trial is for adults aged 18-75 with HLA-A2+ and MAGE-A4 positive recurrent ovarian cancer who've had specific prior treatments, including platinum-based chemotherapy. They must have an ECOG performance status of 0 or 1, be fit for leukapheresis, not pregnant, agree to contraception if applicable, and have adequate organ function. Exclusions include certain heart conditions, uncontrolled illnesses, active infections like HIV/HBV/HTLV or hepatitis C virus (HCV), autoimmune diseases unless stable on treatment, recent major surgery without full recovery from any related toxicities.

What is being tested?

The study tests ADP A2M4CD8 cells alone and combined with Nivolumab in patients with ovarian cancer that expresses a protein called MAGE-A4. It's an open-label phase 2 trial where participants are randomly assigned to receive either the monotherapy or combination therapy to assess clinical outcomes.

What are the potential side effects?

Potential side effects may include immune system reactions due to genetically modified cells or Nivolumab causing inflammation in organs; infusion-related reactions; fatigue; blood disorders; increased risk of infection; allergic responses similar to those seen with fludarabine and cyclophosphamide used during the study.

Eligibility Criteria

Inclusion Criteria

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

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I meet all the requirements for the study before my leukapheresis and chemotherapy.

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My first treatment included at least 3 rounds of platinum and taxane chemotherapy.

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I have a BRCA mutation and have been treated with a PARP inhibitor.

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My tumor shows high MAGE-A4 levels as confirmed by a central lab.

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

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My heart pumps blood effectively, meeting the minimum health standard.

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I am between 18 and 75 years old.

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I have received bevacizumab treatment.

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I have a confirmed diagnosis of advanced ovarian, peritoneal, or fallopian tube cancer.

Exclusion Criteria

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

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I need oxygen support for heart or lung issues.

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I have a family or personal history of prolonged QT syndrome or torsade de pointes.

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My high blood pressure is not controlled, even with medication.

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I have not had significant bleeding or blood disorders in the last 2 months.

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My heart or the sac around it has been affected by cancer.

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I've needed fluid drained from my abdomen or chest twice in the last month.

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I have heart rhythm problems that are not well-controlled.

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I have an active hepatitis C infection confirmed by a test.

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I have severe heart failure.

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I haven't had a stroke or similar brain event in the past 6 months.

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I was hospitalized for a blocked intestine in the last 2 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3.6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3.6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3.6 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

To evaluate the anti-tumor activity of genetically modified autologous T-cells (ADP-A2M4CD8) as monotherapy and in combination with nivolumab in HLA-A*02 positive subjects with MAGE-A4 positive recurrent ovarian cancer

Secondary study objectives

Durable Response (DR)

Duration of Response (DOR)

Levels of serum CA125

+7 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Autologous genetically modified ADP-A2M4CD8 cells in combination with NivolumabExperimental Treatment1 Intervention

Group II: Autologous genetically modified ADP-A2M4CD8 cellsExperimental Treatment1 Intervention

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, such as adoptive cell therapy and immune checkpoint inhibitors, work by enhancing the body's immune response against cancer cells. Adoptive cell therapy, like ADP A2M4CD8, involves engineering T-cells to target specific cancer antigens, such as MAGE-A4, thereby improving the immune system's ability to attack the cancer. Nivolumab, a PD-1 inhibitor, blocks the PD-1 pathway that cancer cells use to evade immune detection, reactivating T-cells to recognize and destroy cancer cells. These targeted therapies are significant for ovarian cancer patients as they offer more precise and potentially more effective treatment options compared to traditional methods.