ADP-A2M4CD8 + Nivolumab for Ovarian Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the effectiveness of a new cell therapy, ADP-A2M4CD8, both alone and combined with the medication nivolumab, in treating recurrent ovarian cancer. It targets patients whose cancer is positive for a specific protein called MAGE-A4 and who carry certain genetic markers (HLA-A2+). Suitable candidates have high-grade serous or endometrioid ovarian cancer that has returned after specific previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to significant advancements in ovarian cancer therapy.

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.

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

Research has shown that ADP-A2M4CD8, a genetic therapy using the patient’s own cells, is generally safe for individuals with various cancers, including ovarian cancer. Studies have found that most patients tolerate this treatment well, although some side effects can occur, as with any treatment. For instance, trials with head and neck cancer patients demonstrated that the treatment was safe and side effects were manageable.

When combined with Nivolumab, an immunotherapy drug, ADP-A2M4CD8 has also shown promising safety results. Previous studies on this combination found that patients generally tolerated it well, though specific side effects were not detailed. Nivolumab is already approved for other cancers, indicating that its safety is well understood.

In this trial phase, the researchers are confirming the treatment's safety, and early results are positive. This indicates that the treatment has passed initial safety tests, instilling confidence in its safety for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ADP-A2M4CD8 for ovarian cancer because it uses a cutting-edge approach called adoptive cell therapy. This treatment involves genetically modifying a patient's own T-cells to better recognize and attack cancer cells, offering a more personalized approach than traditional chemotherapy or surgery. When combined with Nivolumab, an immune checkpoint inhibitor, it may enhance the immune system's ability to fight the cancer, potentially leading to improved outcomes. Unlike standard treatments that often have broad effects on the body, this combination aims to target the cancer more specifically, which could lead to fewer side effects and better quality of life for patients.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that ADP-A2M4CD8 yields promising results in treating certain tumors. In one study, patients with advanced ovarian cancer who had already undergone multiple treatments experienced a 44% response rate with just one dose of ADP-A2M4CD8. Nearly half of these patients saw their tumors shrink. In this trial, some participants will receive ADP-A2M4CD8 alone, while others will receive it with Nivolumab to determine if it can enhance results. This combination targets a protein called MAGE-A4, commonly found in cancer cells, and aims to help the immune system fight cancer more effectively. Although more research is needed, early results offer hope for those with recurring ovarian cancer. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.TPS363

A phase 2, open-label study of ADP-A2M4CD8 SPEAR T ... SURPASS-2 (NCT04752358) is a phase 2, open-label, single-arm trial to assess safety and efficacy of ADP-A2M4CD8 SPEAR T-cells in HLA-A*02–positive patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11815873/

Adoptive T Cell Therapy Targeting MAGE-A4 - PMC Though the ADP A2M4 TCR demonstrated excellent effectiveness against certain MAGE A4-associated tumors in recent trials, further advances in the development of ...

3. jitc.bmj.com jitc.bmj.com/content/8/Suppl_3/A231.1

379 Initial safety, efficacy, and product attributes from the ... Conclusions ADP-A2M4CD8 SPEAR T-cells have shown an acceptable safety profile and pts with EGJ cancer and head and neck cancer have demonstrated ...

4. adaptimmune.com adaptimmune.com/investors-and-media/news-center/press-releases/detail/231/adaptimmune-reports-positive-data-in-its-surpass-trial

Adaptimmune Reports Positive Data in its SURPASS Trial 44% Objective Response Rate (ORR) with a single dose of ADP-A2M4CD8 in 25 heavily pre-treated patients with late-stage ovarian, urothelial, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04044859

NCT04044859 | ADP-A2M4CD8 as Monotherapy or in ... This study will investigate the safety and tolerability of ADP-A2M4CD8 T-cell therapy in subjects who have the appropriate human leukocyte antigen (HLA) and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04044859

NCT04044859 | ADP-A2M4CD8 as Monotherapy or in ... This study will investigate the safety and tolerability of ADP-A2M4CD8 T-cell therapy in subjects who have the appropriate human leukocyte antigen (HLA) and ...