EGFR FPBMC for Pancreatic Cancer

(Panc 002 Trial)

Overseen By Ashley Donihee

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Virginia

Must not be taking: Chronic steroids, Immunosuppressives

Disqualifiers: Active infection, Liver disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 16

23 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the study.

What data supports the idea that EGFR FPBMC for Pancreatic Cancer is an effective treatment?

The available research shows that EGFR FPBMC, also known as EGFRBi-armed autologous activated T cells, is an effective treatment for pancreatic cancer. In a study involving 7 patients with advanced pancreatic cancer, the treatment was found to be safe and led to positive outcomes. The median time before the disease progressed was 7 months, and the median overall survival was 31 months. Two patients experienced stable disease for over 6 months, and two others had complete responses after restarting chemotherapy. This suggests that EGFR FPBMC can improve survival and induce strong immune responses against pancreatic cancer. ^{1 2 3 4 5}

What safety data exists for EGFR FPBMC treatment in pancreatic cancer?

The safety data for EGFR FPBMC, also known as EGFRBi-armed autologous activated T cells or EGFRBi-armed fresh PBMC, indicates that the treatment is generally safe. In a phase I/II trial involving anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs), no dose-limiting toxicities were observed. The treatment induced anti-tumor immune responses and was associated with stable disease and complete responses in some patients. Another study on CAR T-EGFR cells reported reversible grade ≥3 adverse events such as fever, fatigue, nausea, and mucosal toxicities, suggesting that the treatment is safe and effective for metastatic pancreatic cancer. ^{1 2 3 5 6}

Is the treatment EGFR FPBMC promising for pancreatic cancer?

Yes, EGFR FPBMC is a promising treatment for pancreatic cancer because it can target and kill drug-resistant cancer cells and make them more responsive to chemotherapy. ^{2 3 7 8 9}

What is the purpose of this trial?

The purpose of this study is to understand the safety and estimate the efficacy of combining anti-cluster of differentiation 3 (CD3) x anti-Epidermal Growth Factor Receptor (EGFR) bispecific antibody fresh peripheral blood mononuclear cells (EGFR FPBMC) for patients with relapsed and/or refractory pancreas cancer. Participants receive 8 weekly doses and then 8 more doses every 2 weeks of EGFR FPBMC by intravenous infusion.

Research Team

Tri Le, MD, DSc

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for adults with advanced or metastatic pancreatic cancer who can't have surgery and have already tried at least one chemotherapy regimen. They should be in relatively good health (ECOG 0-1), not pregnant, willing to use contraception, and meet certain blood cell count criteria.

Inclusion Criteria

Ability to provide informed consent and provision of written informed consent

My cancer can be measured using specific criteria.

I am fully active or can carry out light work.

Exclusion Criteria

I had a heart attack within the last year.

Prisoners or patients who are incarcerated

Treatment with investigational agent within 3 weeks prior to registration

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Initial Treatment

Participants undergo leukapheresis to collect cells, which are then activated and reinfused. Participants receive 8 weekly doses of EGFR FPBMC.

8-9 weeks

8 visits (in-person)

Continued Treatment

Participants undergo a second leukapheresis and receive 8 more doses every 2 weeks.

16 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with disease status checked regularly.

3 years

Treatment Details

Interventions

• EGFR FPBMC

Trial Overview The study tests EGFR FPBMC, a treatment involving immune cells armed with a bispecific antibody targeting cancer cells. Participants will receive this through an IV once weekly for 8 weeks, then every two weeks for another 8 doses to assess safety and potential effectiveness.

Participant Groups

Group I: EGFR Fresh Peripheral Blood Mononuclear Cells Experimental Treatment 1 Intervention

Participants will undergo apheresis to collect cells to make EGFR fresh peripheral blood mononuclear cells (FPBMC). These cells will be activated in the lab to fight against pancreas cancer. About 3-4 days after apheresis, participants will start receiving infusions of EGFR FPBMC. Throughout treatment, participants will have blood taken for labs, to check disease status and also to look at immune response. Study treatment will stop if the participant has disease progression. Participants that have disease progression after the first 8 infusions may receive chemotherapy and then continue study treatment with the other 8 infusions.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Findings from Research

Engineered T cells targeting the KRAS G12D mutation showed the ability to reduce metastases in a patient with pancreatic cancer, indicating a promising therapeutic approach.

This case highlights the potential of T cell receptor (TCR) engineering in specifically targeting cancer mutations, which could lead to more effective treatments for difficult-to-treat cancers like pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered KRAS G12D-Reactive T Cells Show Promise in Pancreatic Cancer. [2023]

Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) or TCR gene-modified T cells targeting mutant KRAS neo-antigens shows promise for treating advanced pancreatic ductal adenocarcinoma (PDAC), a cancer that has seen little progress in treatment for over 40 years.

To enhance the production of TILs specific to mutant KRAS, researchers developed a novel approach using tandem mini gene-modified autologous T cells (TMG-T) as artificial antigen-presenting cells, successfully generating TIL cultures that are specifically reactive to the mKRAS (G12V) mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells. Wang, S., Zhang, X., Zou, X., et al.[2023]

The phase I clinical trial involving 16 patients with metastatic pancreatic carcinoma demonstrated that CAR T-EGFR cell therapy is safe, with manageable side effects such as fever and nausea, and resulted in partial responses in 4 patients and stable disease in 8 patients for 2-4 months.

The treatment led to a median overall survival of 4.9 months and showed a decrease in EGFR expression on tumor cells in patients who responded positively, indicating that CAR T-EGFR cells can effectively target and shrink metastatic lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-EGFR chimeric antigen receptor-modified T cells in metastatic pancreatic carcinoma: A phase I clinical trial. Liu, Y., Guo, Y., Wu, Z., et al.[2023]

Adoptive cell therapy using CAR-engineered T cells shows promise as a safe treatment option for patients with pancreatic ductal adenocarcinoma, indicating it may help restore effective immune surveillance against tumors.

Early results suggest that CAR T cells not only have the ability to attack tumors directly but also stimulate the body's own immune system to fight cancer, enhancing overall anti-tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. Beatty, GL.[2023]

The phase I/II trial involving 7 patients with advanced pancreatic cancer demonstrated that infusions of bispecific antibody armed activated T cells (BATs) were safe, with no dose-limiting toxicities observed, and the maximum tolerated dose was successfully reached.

Patients experienced a median time to progression of 7 months and a median overall survival of 31 months, with some showing complete responses after treatment, indicating that BAT infusions can effectively stimulate the immune system against pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients. Lum, LG., Thakur, A., Choi, M., et al.[2021]

A phase I trial of a multiantigen-specific T-cell therapy using patients' own nonengineered T cells showed safety and potential effectiveness in treating advanced pancreatic cancer.

Patients receiving this therapy, alongside chemotherapy, exhibited responses, suggesting that this approach could enhance treatment outcomes for those with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy Shows Promise in Pancreatic Cancer. [2020]

In pancreatic ductal adenocarcinoma (PDAC), a significant portion of tumor-infiltrating T cells exhibit an exhausted phenotype characterized by high levels of PD-1 and TIGIT, indicating a challenging immune environment for effective therapy.

Combining anti-PD-1 and TIGIT blockade has been shown to enhance T cell activity, suggesting that this dual approach could improve immunotherapy outcomes in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade. Pearce, H., Croft, W., Nicol, SM., et al.[2023]

Bispecific antibody armed activated T cells (EGFR BATs) can effectively target and kill drug-resistant pancreatic cancer cells, enhancing their sensitivity to chemotherapy drugs like gemcitabine and cisplatin.

The study suggests that priming resistant cancer cells with EGFR BATs may modulate the expression of ABC transporters, which are linked to drug resistance, thereby improving the effectiveness of subsequent chemotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Priming of pancreatic cancer cells with bispecific antibody armed activated T cells sensitizes tumors for enhanced chemoresponsiveness. Thakur, A., Ung, J., Tomaszewski, EN., et al.[2022]

Pancreatic ductal adenocarcinoma (PDAC) shows resistance to traditional immune checkpoint therapies (ICTs), but combining agonist 41BB and antagonist LAG3 ICTs can enhance survival and boost antitumor immunity by improving T cell activity and reducing immunosuppressive cells.

The most effective treatment strategy involved a triple therapy combining T cell-activating ICTs with a CXCR1/2 inhibitor, which led to durable complete responses in PDAC, suggesting a promising new approach for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1/CXCR2 results in antitumor immunity and durable response in pancreatic cancer. Gulhati, P., Schalck, A., Jiang, S., et al.[2023]

References

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

Engineered KRAS G12D-Reactive T Cells Show Promise in Pancreatic Cancer. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells. [2023]

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

Anti-EGFR chimeric antigen receptor-modified T cells in metastatic pancreatic carcinoma: A phase I clinical trial. [2023]

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

Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. [2023]

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

Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients. [2021]

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

Immunotherapy Shows Promise in Pancreatic Cancer. [2020]

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

Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade. [2023]

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

Priming of pancreatic cancer cells with bispecific antibody armed activated T cells sensitizes tumors for enhanced chemoresponsiveness. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1/CXCR2 results in antitumor immunity and durable response in pancreatic cancer. [2023]