Armed Activated T-Cells for Pancreatic Cancer

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

7 Participants Needed

Trial Summary

What is the purpose of this trial?

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 cells) for people with advanced pancreatic cancer who have already received first-line standard chemotherapy.

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.

What data supports the effectiveness of this treatment for pancreatic cancer?

Research shows that bispecific antibody armed activated T cells can target and kill drug-resistant pancreatic cancer cells and make them more responsive to chemotherapy, suggesting this treatment could be effective for pancreatic cancer. ^{1 2 3 4 5}

Is the treatment with armed activated T-cells generally safe for humans?

The research does not provide specific safety data for armed activated T-cells in humans, but it shows that similar bispecific antibodies have been used in preclinical models to target cancer cells effectively. This suggests potential for safety, but human-specific safety data is not available in the provided studies. ^{1 2 6 7 8}

How is the treatment with anti-EGFR-bispecific antibody armed activated T-cells different from other pancreatic cancer treatments?

This treatment is unique because it uses bispecific antibodies to specifically recruit and activate T-cells to target and kill cancer cells, potentially offering a more targeted approach compared to traditional therapies. It leverages the body's immune system to fight the cancer, which is different from standard chemotherapy or radiation treatments. ^{2 5 9 10 11}

Research Team

Kenneth H Yu, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

References

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

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

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

Overcoming resistance to HER2-targeted therapy with a novel HER2/CD3 bispecific antibody. [2021]

3. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer. [2023]

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

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

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

Novel bispecific antibodies increase γδ T-cell cytotoxicity against pancreatic cancer cells. [2021]

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

Immuno-targeting of pancreatic cancer stem cells: A new therapeutic strategy against a devastating disease? [2021]

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

Expression of inhibitory receptors on intratumoral T cells modulates the activity of a T cell-bispecific antibody targeting folate receptor. [2021]

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

Bispecific Antibodies Enable Synthetic Agonistic Receptor-Transduced T Cells for Tumor Immunotherapy. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

CD3 x CD28 cross-interacting bispecific antibodies improve tumor cell dependent T-cell activation. [2017]

11. Germany pubmed.ncbi.nlm.nih.gov

A Th1 cytokine-enriched microenvironment enhances tumor killing by activated T cells armed with bispecific antibodies and inhibits the development of myeloid-derived suppressor cells. [2021]