Allogeneic CAR-T Cells for Cancer

Recruiting at 14 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

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new therapy using modified immune cells in adults with advanced cancers. The treatment aims to target and destroy cancer cells with a specific marker found in various cancers, including breast cancer.

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.

What data supports the idea that Allogeneic CAR-T Cells for Cancer (also known as: P-MUC1C-ALLO1 CAR-T cells, P-MUC1C-ALLO1) is an effective treatment?

The available research shows that Allogeneic CAR-T Cells for Cancer, specifically targeting MUC1, have demonstrated effectiveness in controlling tumor growth in various cancer models. For instance, CAR T cells targeting the Tn glycoform of MUC1 showed strong tumor-killing ability in models of T cell leukemia and pancreatic cancer. Additionally, in breast cancer models, CAR T cells targeting MUC1 exhibited high efficiency and specificity against cancer cells, with improved performance when using a specific signaling domain. These findings suggest that this treatment can effectively target and reduce cancer cells in different types of tumors. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment P-MUC1C-ALLO1 CAR-T cells for cancer?

Research shows that CAR T cells targeting MUC1, a protein often found in high amounts on cancer cells, can effectively attack and control tumor growth in various cancers, including breast and pancreatic cancer. These studies suggest that targeting MUC1 with CAR T cells, like P-MUC1C-ALLO1, could be a promising approach for treating cancers that express this protein. ^{1 2 3 4 5}

What safety data is available for Allogeneic CAR-T Cells for Cancer?

The provided research does not contain specific safety data for Allogeneic CAR-T Cells, including P-MUC1C-ALLO1 CAR-T cells. The studies focus on immune checkpoint inhibitors and their associated immune-related adverse events, which are not directly related to CAR-T cell therapies. Therefore, no relevant safety data for Allogeneic CAR-T Cells is available in the provided research. ^{6 7 8 9 10}

Is the treatment P-MUC1C-ALLO1 CAR-T cells a promising treatment for cancer?

Yes, P-MUC1C-ALLO1 CAR-T cells are a promising treatment for cancer. They target a specific protein called MUC1, which is found in many types of cancer cells. This treatment has shown the ability to specifically attack and kill cancer cells, control tumor growth, and enhance the immune response against tumors. It has been effective in various cancer models, including breast, pancreatic, and lung cancers, making it a hopeful option for treating these diseases. ^{1 2 11 12 13}

What makes the P-MUC1C-ALLO1 treatment unique for cancer?

P-MUC1C-ALLO1 is unique because it uses allogeneic (donor-derived) CAR-T cells to target the MUC1 protein, which is often overexpressed and altered in many cancers. This approach aims to overcome the challenges of the tumor microenvironment that typically suppresses immune responses, making it a novel strategy compared to traditional treatments. ^{1 2 11 12 13}

Research Team

Rajesh Belani, M.D.

Principal Investigator

Sponsor Executive Medical Director

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

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

Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. [2022]

3. Egypt pubmed.ncbi.nlm.nih.gov

An In Vitro Comparison of Costimulatory Domains in Chimeric Antigen Receptor T Cell for Breast Cancer Treatment. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Identification and characterization of agonist epitopes of the MUC1-C oncoprotein. [2021]

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

MUC1-C promotes the suppressive immune microenvironment in non-small cell lung cancer. [2021]

6. Japan 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. [2023]

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

Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors. [2021]

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

Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis. [2018]

10. Singapore pubmed.ncbi.nlm.nih.gov

Management of immune checkpoint inhibitor-related adverse events: A review of case reports. [2021]

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

Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. [2022]

12. United States 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. [2020]

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

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells. [2021]