EGFR BATs for Pancreatic Cancer

Overseen By Ashley Donihee

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Virginia

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: HIV, Hepatitis, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 16

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with locally advanced or metastatic pancreatic cancer who have already undergone chemotherapy. The treatment, called EGFR BATs, uses specially modified T-cells to target cancer cells. The goal is to determine if this approach can safely control cancer growth. This trial may suit those whose pancreatic cancer has not responded well to previous chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that EGFR BATs are likely to be safe for humans?

Research has shown that EGFR BATs, a new treatment for pancreatic cancer, have been well-tolerated in earlier studies. Patients receiving these specially designed T cells did not experience serious side effects that would halt treatment, indicating they could handle the treatment without major issues.

The treatment boosts the body's immune system to fight cancer cells. Early reports suggest it might help people with pancreatic cancer live longer. Since this clinical trial is in its early stages, it primarily aims to confirm the treatment's safety in humans. These trials typically determine a safe dose before progressing to larger studies to test efficacy.

These findings suggest that EGFR BATs are generally safe for patients, but like all treatments, there may be some risks. It's always important to consult a healthcare professional about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about EGFR BATs for pancreatic cancer because it represents a novel approach that harnesses the power of the immune system. Unlike traditional chemotherapy treatments, which directly target and kill cancer cells, EGFR BATs use a patient's own T-cells that are activated and armed with EGFR Biarmed T-cells to seek out and attack cancer cells. This method has the potential to be more precise and less harmful to healthy cells, potentially leading to fewer side effects. Moreover, by using the body’s immune system, EGFR BATs could offer a more sustainable and robust defense against cancer recurrence.

What evidence suggests that EGFR BATs might be an effective treatment for pancreatic cancer?

Research has shown that EGFR BATs, the treatment under study in this trial, may help treat pancreatic cancer. In one study, all five patients who received EGFR BATs lived for more than a year. Another study found that two patients had their disease remain stable for over two months and nearly two years, respectively. EGFR BATs target specific cancer cells in the pancreas, aiming to harness the body's immune system to fight cancer more effectively. These early results suggest that EGFR BATs could be a promising treatment option for advanced pancreatic cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Tri Le, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

Adults with pancreatic adenocarcinoma who've had at least one chemo treatment can join this trial. They should have a life expectancy of over 3 months, be in good physical condition, and not planning to get pregnant or father a child. People with serious health issues, recent surgeries, active infections, certain drug treatments within the last few weeks or other cancers in the past 5 years are excluded.

Inclusion Criteria

I have pancreatic cancer that has spread and received chemotherapy.

You are expected to live for at least 3 more months.

I am willing to use effective birth control.

Exclusion Criteria

Treatment with any investigational agent within 14 days prior to first study intervention (apheresis) for protocol therapy

Capability of being compliant, as determined by the PI and investigator team

History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3-4 weeks

1 visit (in-person)

Leukapheresis and T-cell Activation

White blood cells are collected and T-cells are activated and armed with bispecific antibodies

2 weeks

1 visit (in-person)

Bridging Chemotherapy

Participants receive one dose of chemotherapy prior to EGFR BATs infusion

1-2 weeks

1 visit (in-person)

Treatment

Participants receive EGFR BATs infusions twice weekly or weekly for a total of 8 or 4 infusions respectively

4 weeks

8 visits (in-person) or 4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

5 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• EGFR BATs

Trial Overview The trial is testing EGFR BATs (a type of immune cell therapy) after standard chemotherapy for pancreatic cancer. Phase Ib will find a safe dose through 8 infusions twice weekly for up to 6 subjects. Phase II will assess how well this works in about 22 patients.

How Is the Trial Designed?

Group I: EGFR BATs after standard of care chemo Experimental Treatment 1 Intervention

Subjects will undergo apheresis to collect peripheral blood mononuclear cells. Cells will be cultured for up to 2 weeks before activated T-cells will be harvested, armed with EGFR Biarmed activated T-cells, washed to remove unbound EGFRBi, and cryopreserved. Subjects will then receive one dose of standard of care chemotherapy prior to receiving EGFR BATs.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

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]

EGFR inhibitors significantly improve objective response rates (ORR), disease control rates (DCR), and progression-free survival (PFS) in advanced non-small cell lung cancer patients with EGFR mutations compared to non-targeted chemotherapy, based on a review of 21 studies involving 4,250 patients.

Despite the improved response and control rates with EGFR inhibitors, overall survival (OS) did not show significant differences compared to non-targeted chemotherapy or older EGFR inhibitors, indicating that better short-term outcomes do not necessarily translate to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis. Dang, A., Dang, S., Vallish, BN.[2021]

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance progression-free and overall survival in patients with non-small cell lung cancer (NSCLC) who have activating mutations in the EGFR gene.

Despite their efficacy, EGFR-TKIs can cause several adverse events, such as diarrhea, liver toxicity, and skin issues, which can negatively impact patients' quality of life and adherence to treatment; therefore, managing these side effects is crucial for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of EGFR-TKIs for EGFR mutation-positive non-small cell lung cancer. Zhou, JY., Liu, SY., Wu, YL.[2021]

In a pooled analysis of 21 clinical trials involving 1468 patients with EGFR mutation-positive non-small cell lung cancer, afatinib was found to cause significantly more severe adverse events, such as rash and diarrhea, compared to erlotinib and gefitinib.

Gefitinib was associated with a higher frequency of severe hepatotoxicity compared to the other two drugs, while the overall rates of severe interstitial lung disease were low and similar across all three EGFR-TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Takeda, M., Okamoto, I., Nakagawa, K.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03269526

BATs Treatment for Pancreatic Cancer, Phase Ib/II This protocol will confirm toxicities and estimate the clinical efficacy of combining anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7480816/

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

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.4108

Targeting advanced pancreatic cancer with activated t cells ... In summary, 5 of 5 pts in the phase I survived > 1 year. In the phase II study, two pts have stable disease at 2.3 and 21.5 months, respectively ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-00623

EGFR-BATs in Treating Participants with Locally Advanced ... The EGFR-BATs antibody is able to react against pancreatic cancer. It works by seeking out certain tumor cells like on pancreatic tumor cells that have a ...

5. clinicaltrial.be clinicaltrial.be/en/details/4566?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

A Study of Armed, Activated T-Cells in Patients With Adva... The purpose of this study is to find the safest dose and identify any bad side effects of EGFR-BATs (bispecific antibody-armed activated T ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32939319/

Clinical and immune responses to anti-CD3 x anti-EGFR ... Conclusions: Infusions of BATs are safe, induce endogenous adaptive anti-tumor responses, and may have a potential to improve overall survival.

7. asco.org asco.org/abstracts-presentations/ABSTRACT211431

Targeting advanced pancreatic cancer with activated t cells ... Background: Conventional chemotherapy (CT) for advanced pancreatic cancer (PC) is associated with dismal response rates and poor survival.

8. tandfonline.com tandfonline.com/doi/full/10.1080/2162402X.2020.1773201

Clinical and immune responses to anti-CD3 x anti-EGFR ... Results: There were no dose-limiting toxicities (DLTs), and the targeted dose of 80 × 109 BATs was met. The median TTP is 7 months, and the ...