Armed Activated T-Cells for Pancreatic Cancer

Not currently recruiting at 1 trial location

Overseen By Eileen M O'Reilly, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: Brain metastasis, Immunodeficiency, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EGFR-BATs (anti-EGFR-bispecific antibody armed activated T-cells), which are special activated T-cells, to determine the safest dose and identify any side effects. It targets individuals with advanced pancreatic cancer who have tried standard chemotherapy but require further assistance. Participants should have pancreatic cancer that has spread and have experienced disease progression during or shortly after chemotherapy. This trial offers an opportunity for those who have already undergone at least one round of chemotherapy and seek additional treatment options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, giving participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

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 treatment.

Is there any evidence suggesting that anti-EGFR-bispecific antibody armed activated T-cells are likely to be safe for humans?

Research has shown that treatment using EGFR-BATs, special immune cells designed to target cancer, is generally safe. Studies indicate that patients tolerate these infusions well. These cells assist the body's immune system in fighting cancer cells, potentially extending patients' lives. Previous studies have reported no major safety issues. However, as this is an early phase study, the primary goal is to determine the safest dose and monitor for any side effects. While past results are encouraging, the treatment is still undergoing careful safety testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Unlike the standard treatments for pancreatic cancer, which typically include chemotherapy and radiation, the anti-EGFR-bispecific antibody armed activated T-cells offer a novel approach. These treatments work by harnessing the body's immune system, combining T-cells with an antibody that targets the EGFR protein often overexpressed in cancer cells. This dual-targeting mechanism could potentially enhance the precision of cancer cell destruction while sparing healthy cells. Researchers are excited because this approach might improve effectiveness and reduce side effects compared to traditional therapies.

What evidence suggests that anti-EGFR-bispecific antibody armed activated T-cells might be an effective treatment for pancreatic cancer?

Research has shown that a new treatment using anti-EGFR-bispecific antibody-armed activated T-cells may help fight advanced pancreatic cancer. In one study, patients who received these T-cells lived for a median of 31 months, with some experiencing stable disease for over two years. This treatment transforms T-cells, part of the immune system, into cancer-fighting cells that target specific proteins on cancer cells. While traditional chemotherapy often proves ineffective, this new approach offers hope for a more effective treatment. ^{2 3 6 7 8}

Who Is on the Research Team?

Kenneth H Yu, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced pancreatic cancer who've had first-line chemo. They should have stable or progressing disease after treatment, good performance status (able to carry out daily activities), and adequate organ function. Pregnant women can't join, nor those breastfeeding or with certain medical conditions that could affect compliance.

Inclusion Criteria

My diagnosis is pancreatic cancer, confirmed by lab tests.

Your body has enough white blood cells to fight off infections.

Your disease can be measured and evaluated using specific criteria.

Exclusion Criteria

I have a serious health condition that could worsen with this treatment.

You are allergic to cetuximab or other similar drugs for EGFR.

I have an ongoing liver condition like cirrhosis or hepatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EGFR-BATs to determine the safest dose and identify side effects

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• anti-EGFR-bispecific antibody armed activated T-cells

Trial Overview

The study tests EGFR-BATs (anti-EGFR-bispecific antibody armed activated T-cells) in patients to determine the safest dose and side effects. Participants must have previously received standard chemotherapy for their condition.

How Is the Trial Designed?

Group I: Pancreatic Adenocarcinoma Experimental Treatment 1 Intervention

Participants have metastatic pancreatic cancer who have received at least first line chemotherapy and have disease progression during or within 6 months of treatment.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

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]

Bispecific antibodies have demonstrated the ability to selectively target and effectively eliminate malignant T cells in both laboratory (in vitro) and living organism (in vivo) settings.

This selectivity and efficacy suggest that bispecific antibodies could be a promising therapeutic approach for treating cancers involving T cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell Malignancies Can Be Targeted by Bispecific Antibody Treatments. [2021]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Clinical and immune responses to anti-CD3 x anti-EGFR ...

Arming anti-CD3 activated T cells with anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) turns each activated T cell into a specific cytotoxic T ...

2.

ascopubs.org

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

Targeting advanced pancreatic cancer with activated t cells ...

In the phase II study, two pts have stable disease at 2.3 and 21.5 months, respectively. The median OS is 31.0 months for all 9 patients.

3.

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. Arming anti-CD3 ...

4.

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 ...

5.

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 ...

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.

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 ...

8.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.4135

Clinical and immune responses using anti-CD3 x ...

Infusions of BATs are safe and induce endogenous adaptive anti-tumor responses. Targeting PC with BATs may stabilize disease, leading to improved OS.