Allogeneic CAR-T Cells for Cancer

Not currently recruiting at 15 trial locations

Overseen By Angie Schinkel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Poseida Therapeutics, Inc.

Must not be taking: Immunosuppressants, Corticosteroids, Monoclonal antibodies

Disqualifiers: Active infection, Autoimmune disease, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called P-MUC1C-ALLO1 CAR-T cells, a type of immunotherapy, to determine its effectiveness for people with advanced or metastatic epithelial-derived cancers. The study will evaluate different doses to identify the safest and most effective amount for patients. It is open to adults who have tried other cancer treatments without success or cannot undergo surgery. Participants should have a cancer diagnosis that cannot be surgically removed or has spread to other parts of the body.

As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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

Yes, you may need to stop some medications. You can't have taken anticancer medications within 2 weeks before starting lymphodepletion, immunosuppressive medications within 2 weeks before receiving P-MUC1C-ALLO1, or systemic corticosteroids within 1 week before receiving P-MUC1C-ALLO1.

Will I have to stop taking my current medications?

The trial requires that you stop taking anticancer medications at least 2 weeks before starting the study's lymphodepletion treatment. You also need to stop taking immunosuppressive medications 2 weeks before and systemic corticosteroids 1 week before the study drug is given.

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

Research has shown that P-MUC1C-ALLO1 CAR-T cells, a therapy using donor cells, have a manageable safety profile. In studies involving patients with advanced or spreading cancers, this treatment has generally been well-tolerated. The therapy targets a specific protein, MUC1-C, found in many cancer cells.

Safety data from trials suggest that while some side effects occur, they can be managed. This is promising for patients who have already tried many other cancer treatments. So far, no severe or unexpected safety issues have been reported. Participants in these studies have experienced typical side effects related to CAR-T cell therapies, but these have been considered manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about P-MUC1C-ALLO1 CAR-T cells because they offer a novel approach to targeting cancer. Unlike traditional cancer treatments like chemotherapy and radiation, which broadly attack rapidly-dividing cells, CAR-T therapy is designed to specifically target cancer cells by using modified T-cells to recognize and destroy them. P-MUC1C-ALLO1 CAR-T cells are allogeneic, meaning they are derived from healthy donors rather than the patient, potentially making them more accessible and quicker to administer. Additionally, the use of Rimiducid in these treatments provides a safety switch, allowing doctors to control and potentially reverse the activity of the CAR-T cells if needed, which adds an extra layer of safety not available in many standard treatments.

What evidence suggests that this trial's treatments could be effective for advanced or metastatic epithelial derived solid tumors?

Research has shown that P-MUC1C-ALLO1 CAR-T cells have strong potential in fighting cancer. In studies, these cells effectively killed cancer cells while leaving normal cells unharmed. Participants in this trial will receive P-MUC1C-ALLO1 CAR-T cells in various dosing regimens, including single and multiple doses, to evaluate their effectiveness. These CAR-T cells are specially designed to target cancer cells with a protein called MUC1-C, common in many solid tumors. Early results suggest that this method may help slow cancer growth. ^{1 2 4 6 7}

Who Is on the Research Team?

Simon Heidegger, M.D.

Principal Investigator

Lead Medical Director, Oncology, Genentech Research Early Development

Are You a Good Fit for This Trial?

Adults with advanced or metastatic solid tumors from a variety of cancers, who have not responded to standard treatments. Participants must be willing to use birth control, have good organ function, and an ECOG performance status of 0-1. They cannot join if they have significant CNS disease, active infections, recent corticosteroid therapy, other malignancies (except low-risk skin cancer), autoimmune diseases, severe heart issues or psychiatric disorders that affect protocol adherence.

Inclusion Criteria

My cancer has grown or spread after my last treatment and can be measured.

You need to have a sample of your tumor stored or agree to have a small piece of your tumor removed for testing.

I am mostly active and can care for myself.

Exclusion Criteria

I have a genetic predisposition to HLH/MAS.

I have a history of serious liver problems.

I have taken or will need immunosuppressive drugs recently or during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive P-MUC1C-ALLO1 CAR-T cells in single or multiple dose cohorts, following lymphodepletion regimen

4 weeks

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety, tolerability, and response after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• P-MUC1C-ALLO1 CAR-T cells

Trial Overview The trial is testing P-MUC1C-ALLO1 CAR-T cells combined with Rimiducid in adults with certain types of advanced cancers. It's a Phase 1 study which means it's early in the clinical trials process and focuses on finding the right dose while checking for safety.

How Is the Trial Designed?

Group I: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M) Experimental Treatment 2 Interventions

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Group II: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E) Experimental Treatment 2 Interventions

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Group III: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C) Experimental Treatment 2 Interventions

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.

Group IV: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1) Experimental Treatment 2 Interventions

* Single ascending A1 dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.

Group V: P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A) Experimental Treatment 2 Interventions

* Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.

Group VI: P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F) Experimental Treatment 2 Interventions

* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen. * Rimiducid may be administered as indicated.

Group VII: P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D) Experimental Treatment 2 Interventions

* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2. * Rimiducid may be administered as indicated.

Group VIII: P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B) Experimental Treatment 2 Interventions

* Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1. * Rimiducid may be administered as indicated.

Who Is Running the Clinical Trial?

Poseida Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

780+

Published Research Related to This Trial

CAR T cells engineered to express the TR2.41BB receptor can effectively overcome the immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) in breast cancer, leading to enhanced tumor cell killing and reduced tumor growth in mouse models.

The TR2.41BB CAR T cells not only restored the cytotoxic activity of CAR T cells against MUC1+ breast cancer cells but also improved T cell proliferation and persistence at the tumor site, suggesting a promising strategy for targeting solid tumors with challenging microenvironments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selectively targeting myeloid-derived suppressor cells through TRAIL receptor 2 to enhance the efficacy of CAR T cell therapy for treatment of breast cancer. Nalawade, SA., Shafer, P., Bajgain, P., et al.[2022]

A retrospective review of adverse events reported to the FDA revealed that PD-1 and PD-L1 inhibitors are associated with an increased risk of tuberculosis (TB) and atypical mycobacterial infection (AMI), with 72 cases of TB and 13 cases of AMI identified among users of these drugs.

The risk of developing TB was found to be 1.79 times higher and the risk of AMI was 5.49 times higher in patients treated with PD-1/PD-L1 inhibitors compared to other FDA-approved drugs, indicating that while these therapies can be effective for cancer, they carry significant risks that clinicians should monitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors. Anand, K., Sahu, G., Burns, E., et al.[2021]

Genetically modified T cells, known as CAR T cells, can effectively target abnormal self-antigens like the Tn glycoform of MUC1, which is found in various cancers, showing promise for solid tumor treatment.

In xenograft models of T cell leukemia and pancreatic cancer, CAR T cells targeting Tn-MUC1 demonstrated significant tumor growth control, highlighting their potential therapeutic efficacy against solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. Posey, AD., Schwab, RD., Boesteanu, AC., et al.[2022]

The study developed a chimeric antigen receptor (CAR) targeting MUC1, a protein commonly overexpressed in over 80% of human cancers, which showed strong binding and effective T cell activation against tumor cells.

In a tumor xenograft model, treatment with engineered T cells targeting MUC1 significantly delayed tumor growth, demonstrating the potential efficacy of this CAR T cell therapy in combating MUC1-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. Wilkie, S., Picco, G., Foster, J., et al.[2022]

Ipilimumab, an antibody that enhances T-cell activation, is effective for treating metastatic melanoma but can cause immune-mediated side effects, including rare cases of ileitis without colitis, as seen in a 54-year-old patient.

The study highlights the need for further research into genetic and epigenetic factors to personalize treatment and minimize adverse effects associated with ipilimumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis. Venditti, O., De Lisi, D., Caricato, M., et al.[2018]

This study highlights the potential of CAR T cell therapies targeting prostate stem cell antigen (PSCA) and mucin 1 (MUC1) in treating non-small-cell lung cancer (NSCLC), showing effective tumor suppression in patient-derived xenograft (PDX) mouse models.

The combination of PSCA- and MUC1-targeting CAR T cells demonstrated enhanced antitumor efficacy, suggesting that targeting multiple antigens could improve treatment outcomes for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells. Wei, X., Lai, Y., Li, J., et al.[2021]

In a study of 16 patients with non-small cell lung cancer receiving immune checkpoint inhibitors (ICIs), higher baseline levels of CD86+ plasmacytoid dendritic cells (pDCs) were linked to the occurrence of immune-related adverse events (irAEs), suggesting a potential biomarker for predicting these side effects.

Additionally, a significant decrease in CD86+pDC levels at weeks 2 and 8 after starting ICIs was observed in patients who experienced irAEs, while higher levels of natural killer (NK) cells were associated with a better overall response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between increased peripheral blood CD86-positive plasmacytoid dendritic cells and immune-related adverse events in patients with non-small cell lung cancer. Karayama, M., Mizoguchi, Y., Inoue, Y., et al.[2023]

Mucin-specific cytotoxic T cells (CTLs) from breast and pancreatic cancer patients can effectively recognize and respond to tumor-associated antigens, specifically those derived from the MUC1 gene, indicating a potential for targeted immunotherapy.

The study successfully established mucin-specific CTL lines using autologous or allogeneic B cells transfected with mucin, demonstrating that these modified B cells can present tumor antigens and be targeted by CTLs, which could enhance the understanding and development of cancer immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA. Jerome, KR., Domenech, N., Finn, OJ.[2020]

Anti-PD-1 treatment can enhance anti-tumor immune responses, but about 50% of patients experience immune-related adverse events (irAEs), which can limit its clinical effectiveness.

Single-cell RNA sequencing revealed that specific T cell populations are linked to different irAEs, suggesting that analyzing these T cells before treatment could help predict which patients are at higher risk for specific toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors. Bukhari, S., Henick, BS., Winchester, RJ., et al.[2023]

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, can lead to immune-related adverse events (irAEs) due to their mechanism of enhancing the immune response against cancer, which can sometimes mistakenly target healthy tissues.

This study reviewed 128 reports involving 239 cases of toxicities associated with these treatments, highlighting the need for careful management of irAEs, as there is currently no standardized approach based on prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. Si, X., Song, P., Ni, J., et al.[2021]

CAR T cells targeting the MUC1 antigen, which is overexpressed in breast cancer, demonstrated high effectiveness in recognizing and attacking MUC1+ cancer cells, showing strong antitumor activity in laboratory tests.

The study found that CAR T cells with the 41BB signaling domain outperformed those with the CD28 domain by enhancing T cell proliferation and reducing suppressive signals, suggesting that 41BB-based CAR T cells could be more effective for treating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment. Khuisangeam, N., Jewmoung, S., Thaiwong, R., et al.[2022]

The study identifies nine potential CD8⁺ T-cell epitopes from the MUC1 oncoprotein, particularly from its C-terminus, which is linked to poor prognosis in various cancers, suggesting a promising target for immunotherapy.

Agonist peptides derived from these epitopes are more effective than native peptides in generating T-cell responses and lysing tumor cells, indicating their potential for enhancing cancer vaccine strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification and characterization of agonist epitopes of the MUC1-C oncoprotein. Jochems, C., Tucker, JA., Vergati, M., et al.[2021]

Targeting the MUC1-C oncoprotein in non-small cell lung cancer (NSCLC) using the inhibitor GO-203 led to decreased levels of PD-L1 and increased levels of interferon-γ (IFN-γ), suggesting a mechanism to enhance immune response against tumors.

The treatment resulted in improved activation and function of CD8+ tumor-infiltrating lymphocytes (TILs), which are crucial for tumor killing, indicating that MUC1-C could be a promising target for reprogramming the tumor microenvironment to improve immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MUC1-C promotes the suppressive immune microenvironment in non-small cell lung cancer. Bouillez, A., Adeegbe, D., Jin, C., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05239143

NCT05239143 | P-MUC1C-ALLO1 Allogeneic CAR-T Cells ... This is an open label, multi-center Phase 1 study that will follow a 3 + 3 design of dose-escalating cohorts of single and multiple doses of P-MUC1C-ALLO1 ...

2. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A761

728 Phase 1 study of P-MUC1C-ALLO1 allogeneic CAR-T ... Results To date, three patients have been treated with P-MUC1C-ALLO1 (esophageal adenocarcinoma, colorectal adenocarcinoma, and breast cancer).

3. poseida.com poseida.com/wp-content/uploads/2023/04/Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting-2021_MUC1C-Poster.pdf

P-MUC1C-ALLO1: A Fully Allogeneic Stem Cell Memory T ... P-MUC1C-ALLO1 demonstrates potent cytotoxicity against tumor cells, and minimal killing of normal MUC1-C-positive human primary cells. In a triple-negative ...

4. esmoiotech.org esmoiotech.org/article/S2590-0188(24)00158-8/fulltext

50P Phase I trial of P-MUC1C-ALLO1 allogeneic CAR-T ... Most adverse events (AEs) were LD or cancer related. The most common Grade ≥3 treatment emergent AEs were neutropenia (88%), leukopenia (47%), lymphopenia (33%) ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02081

Chimeric Antigen Receptor-T Cells in Colorectal Cancer In CRC, allogeneic CAR-T cells have shown promise in early-phase clinical trials. Notably, P-MUC1C-ALLO1 is an allogeneic CAR-T cell product ...

6. poseida.com poseida.com/wp-content/uploads/2023/04/Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting-2022_MUC1C-Phase-1-study.pdf

Phase 1 Study of P-MUC1C-ALLO1 Allogeneic CAR-T ... We have developed a fully allogeneic CAR-T cell therapy, called P-MUC1C-ALLO1, targeting the MUC1-C epitope that is manufactured using non-viral transposon- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12553175/

Genome-edited allogeneic CAR-T cells - PubMed Central - NIH P-MUC1C-ALLO1 is an allogenic CAR-T targeting MUC1-C that uses the ... Early safety results of P-BCMA-ALLO1, a fully allogeneic ...