TAA-T Cells + Nivolumab for Lymphoma

Overseen By Fahmida Hoq, MBBS, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Catherine Bollard

Must be taking: Nivolumab

Must not be taking: ATG, Campath

Disqualifiers: Uncontrolled infections, Active HIV, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with certain types of lymphoma that have returned or are difficult to treat. It combines TAA-T cells, specialized immune cells targeting cancer, with Nivolumab, a drug that enhances the immune system's ability to attack cancer. Researchers aim to determine the safety of this combination and identify potential side effects. The trial seeks participants who have not succeeded with other treatments for Hodgkin Lymphoma or Diffuse Large B-Cell Lymphoma, or those at high risk of relapse after a stem cell transplant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment combination.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a requirement for a two-week washout period (time without taking certain medications) for those receiving Granulocyte colony-stimulating factor (G-CSF) before procurement.

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

Research has shown that using TAA-T cells with Nivolumab is generally safe for people with relapsed or hard-to-treat Hodgkin's lymphoma. Studies found that this combination does not cause major side effects that would require stopping the treatment. In the trials, patients handled the treatment well, and many showed positive responses. The treatment worked for a while without causing serious harm. Although still under investigation, early findings suggest this treatment is promising for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard lymphoma treatments that typically involve chemotherapy and radiation, the combination of Nivolumab and TAA-T cells offers a unique approach by harnessing the body’s immune system. Nivolumab is an immune checkpoint inhibitor that helps T-cells attack cancer cells more effectively, while TAA-T cells are specially engineered to target specific tumor-associated antigens. This dual mechanism not only aims to directly engage and destroy cancer cells but also potentially provides longer-lasting protection against the disease. Researchers are excited because this approach could lead to more personalized and less toxic lymphoma treatments.

What evidence suggests that this trial's treatments could be effective for relapsed lymphoma?

This trial will evaluate the combination of Nivolumab with TAA-T cells for treating relapsed lymphomas. Research has shown that this combination may help treat relapsed lymphomas. In one study, 7 out of 8 patients with active disease experienced no worsening of their cancer six weeks after receiving TAA-T cells. Another study found that using Nivolumab in different situations led to an 85% survival rate at six months. Nivolumab alone has proven safe and effective for various types of lymphoma, with high survival rates in some trials. These findings suggest that using Nivolumab with TAA-T cells could effectively treat hard-to-treat lymphomas. ^{1 4 6 7 8}

Who Is on the Research Team?

Boyu Hu, MD

Principal Investigator

UTAH

Are You a Good Fit for This Trial?

This trial is for people over 12 with certain types of lymphoma that have come back or didn't respond to treatment. They should not be pregnant, have HIV, or had a solid organ transplant. Participants need a minimum level of physical ability and blood cell counts, haven't used some therapies recently, and agree to use birth control.

Inclusion Criteria

I have mild side effects from Nivolumab, manageable with treatment.

You have Hodgkin's lymphoma.

Pregnancy or lactating

Exclusion Criteria

I do not have any infections that are not responding to treatment.

I have mild or noticeable side effects from previous treatments.

You have received any experimental treatments within 28 days before being screened for this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Safety Monitoring

Initial safety monitoring or DLT group with 6 patients enrolled to evaluate safety of TAA-T cells and Nivolumab

6 weeks

Multiple visits for safety assessments

Treatment

Patients receive Nivolumab at least 8 weeks prior to first TAA-T cell infusion, followed by two TAA-T cell infusions given 2 weeks apart

12 weeks

Regular visits every 2 weeks for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including tumor response assessment

1 year

Periodic imaging and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• TAA-T cells

Trial Overview The study tests TAA-T cells combined with the PD-1 inhibitor Nivolumab in two groups: those with measurable disease after relapse (Group A) and as additional therapy post-stem cell transplant for high-risk patients (Group B). It aims to assess safety and potential benefits against lymphoma.

How Is the Trial Designed?

Group I: Nivolumab with TAA-T cell Experimental Treatment 2 Interventions

Patients will receive doses of Nivolumab at a minimum of 8 weeks prior to first TAA-T cell infusion and additional dose(s) of Nivolumab will be given after 4 weeks following second TAA-T cell infusion starting at week 7 from first infusion of TAA-T.If patient meets eligibility criteria for TAA-T cell infusion, the patient will receive two TAA-T cell infusions given 2 weeks apart

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

13

Recruited

290+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8791594/

Tumor-associated antigen–specific T cells with nivolumab ... Although efficacy was not the primary end point of this study, 7 of 8 patients with active disease achieved SD at 6 weeks after the TAA-T infusion. One patient ...

2. astctjournal.org astctjournal.org/article/S2666-6367(24)00692-4/fulltext

Addition of Nivolumab Tailored by Expansion of CAR-T ... The cumulative incidence of overall survival at 6 and 12 months were 85% (95% CI 72%-98%) and 51% (95% CI 31%-71%), respectively. Nivolumab ...

3. researchgate.net researchgate.net/figure/Safety-and-Outcomes-of-patients-receiving-TAA-T-Nivolumab_tbl2_354456341

Safety and Outcomes of patients receiving TAA-T± ... Despite these advances, upwards of 10% of patients experience progressive disease after initial therapy with an even higher percentage relapsing. Until recently ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/hodgkin-lymphoma-nivolumab-avd-first-line

Nivolumab and AVD the New Standard in Hodgkin ... Two years after starting treatment, about 92% of trial participants randomly assigned to the nivolumab–AVD group were alive without their cancer ...

5. ashpublications.org ashpublications.org/ashclinicalnews/news/2728/Nivolumab-Safe-and-Effective-for-Treatment-of

Nivolumab Safe and Effective for Treatment of Various ... Recent results from a phase Ib study published in the Journal of Clinical Oncology show that the drug was well tolerated in patients with a variety of lymphoma ...

6. innovationdistrict.childrensnational.org innovationdistrict.childrensnational.org/t-cell-therapy-with-nivolumab-safe-for-hodgkins-lymphoma/

T-cell therapy with nivolumab safe for Hodgkin's lymphoma It is safe for patients with relapsed or refractory Hodgkin's lymphoma (HL) to receive a novel tumor-associated antigen specific T-cell therapy (TAA-T)

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118723914

Tumor Associated Antigen Specific T Cells Given in ... TAA-T cells given in combination with Nivolumab were safe when administered to patients with rel/ref HL with prolonged clinical responses (ranging from SD to ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34495306/

Tumor-associated antigen-specific T cells with nivolumab are ... The infusions were safe with no clear dose-limiting toxicities. Patients receiving TAA-Ts as adjuvant therapy remain in continued remission at 3 ...