ADP-A2M4CD8 + Nivolumab for Ovarian Cancer

Recruiting at 35 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Adaptimmune

Must be taking: Bevacizumab, PARP inhibitors

Must not be taking: Corticosteroids, Immunosuppressive therapy

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: Unknown

Duration: 3.6 years

66 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for various treatments before starting the study. For example, cytotoxic chemotherapy requires a 3-week washout, and corticosteroids require a 2-week washout. It's best to discuss your specific medications with the study team to understand any necessary adjustments.

What data supports the effectiveness of the treatment ADP-A2M4CD8 + Nivolumab for ovarian cancer?

Research shows that combining immune therapies like adoptive cell therapy (using a patient's own immune cells) with checkpoint inhibitors (drugs that help the immune system attack cancer) can be safe and potentially effective in ovarian cancer. In one study, this combination led to disease stabilization in several patients, suggesting it might help control the cancer. ^{1 2 3 4 5}

What safety data exists for ADP-A2M4CD8 + Nivolumab treatment?

Nivolumab, also known as Opdivo, has been shown to provide long-term survival benefits in advanced melanoma patients, indicating it is generally safe for use in humans. However, specific safety data for ADP-A2M4CD8 or its other names in ovarian cancer is not provided in the available research. ^{1 2 6 7 8}

What makes the treatment ADP-A2M4CD8 + Nivolumab unique for ovarian cancer?

ADP-A2M4CD8 (uza-cel) is a novel treatment that uses engineered T-cells to specifically target and attack cancer cells, which is different from traditional chemotherapy or standard immunotherapy. When combined with Nivolumab, an anti-PD-1 antibody that helps the immune system recognize and fight cancer, this treatment offers a unique approach by enhancing the body's immune response against ovarian cancer. ^{1 5 6 9 10}

Eligibility Criteria

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.

Inclusion Criteria

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

My ovarian cancer worsened within 6 months after my last platinum-based treatment.

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

Exclusion Criteria

I need oxygen support for heart or lung issues.

I have active hepatitis B or need prophylaxis for viral reactivation.

I do not have any infections that could worsen from a medical procedure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ADP-A2M4CD8 as monotherapy or in combination with nivolumab

3.6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Treatment Details

Interventions

• ADP-A2M4CD8
• Nivolumab

Trial Overview 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.

Participant Groups

Group I: Autologous genetically modified ADP-A2M4CD8 cells in combination with Nivolumab Experimental Treatment 1 Intervention

Group II: Autologous genetically modified ADP-A2M4CD8 cells Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Adaptimmune

Lead Sponsor

Trials

25

Recruited

10,000+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Findings from Research

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a murine model of advanced ovarian cancer, carboplatin treatment alone significantly improved overall survival compared to the combination of carboplatin and anti-PD-L1 monoclonal antibody, indicating that carboplatin may be more effective as a standalone treatment in this context.

Both carboplatin and the combination treatment increased the presence of antitumor CD4+ and CD8+ T cells while reducing immunosuppressive cells, suggesting that carboplatin enhances the immune response against tumors, which could inform future cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model. Zhu, X., Xu, J., Cai, H., et al.[2018]

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

References

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

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

Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation. [2023]

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

PD-1 and PD-L1 expression on TILs in peritoneal metastases compared to ovarian tumor tissues and its associations with clinical outcome. [2021]

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

Adoptive cell therapy in combination with checkpoint inhibitors in ovarian cancer. [2020]

5. Australia pubmed.ncbi.nlm.nih.gov

Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model. [2018]

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

Tissue-Resident Memory-like Lymphocytes Demonstrate Effector Activity in Ovarian Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Tissue-Specific Expression of TIGIT, PD-1, TIM-3, and CD39 by γδ T Cells in Ovarian Cancer. [2022]

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

Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. [2022]