What is the mechanism of action of this treatment?

Common treatments for esophageal cancer include mTOR inhibitors, immune checkpoint inhibitors, and adoptive T cell therapies. mTOR inhibitors like temsirolimus work by blocking the mTOR pathway, which is crucial for cancer cell growth and proliferation, thereby slowing tumor progression. Immune checkpoint inhibitors, such as those targeting PD-1/PD-L1, enhance the immune system's ability to recognize and attack cancer cells by preventing the 'off' signals that tumors use to evade immune detection. Adoptive T cell therapies, like the RAPA-201 cells, involve reprogramming a patient's own T cells to be more effective against cancer. These cells are engineered to resist immunosuppressive signals within the tumor microenvironment and are polarized to a Th1/Tc1 phenotype, which is more effective in killing cancer cells. These mechanisms are significant for esophageal cancer patients as they offer targeted approaches that can potentially improve survival and reduce tumor burden, especially in cases where traditional therapies have failed.

What side effects are associated with this type of intervention?

Common treatments for esophageal cancer, particularly those involving immunotherapy and chemotherapy agents like carboplatin and paclitaxel, as well as mTOR inhibitors like temsirolimus, have several known side effects. Immunotherapy can cause fatigue, rash, diarrhea, and pneumonitis. Chemotherapy agents like carboplatin and paclitaxel often result in nausea, vomiting, neutropenia, thrombocytopenia, and peripheral neuropathy. Temsirolimus may lead to hyperglycemia, hyperlipidemia, rash, and mucositis.

What prior FDA approvals exist?

FDA-approved treatments for esophageal cancer include immune checkpoint inhibitors such as pembrolizumab (Keytruda), which targets PD-1, and nivolumab (Opdivo), which also targets PD-1. These treatments enhance the body's immune response against cancer cells. While there are no direct FDA approvals for therapies exactly like RAPA-201, which involves adoptive transfer of checkpoint-deficient polyclonal T cells, the use of immune checkpoint inhibitors represents a similar approach in leveraging the immune system to combat esophageal cancer.

What other types of research exist?

Promising novel alternatives to RAPA-201 cells for esophageal cancer patients include: 1) Toripalimab plus chemotherapy, which has shown superior progression-free survival and overall survival in the JUPITER-06 trial for advanced esophageal squamous cell carcinoma. 2) Pembrolizumab and nivolumab, which are PD-1 inhibitors providing durable antitumor activity in PD-L1-expressing esophagogastric cancers. 3) Sintilimab combined with chemotherapy, as demonstrated in the ORIENT-15 trial, which has shown efficacy in locally advanced or metastatic esophageal squamous cell carcinoma.

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CAR T-cell Therapy

RAPA-201 Immunotherapy for Solid Cancers

Phase 1 & 2

Recruiting

Research Sponsored by Rapa Therapeutics LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Exposure to an anti-PD-(L)1 monoclonal antibody therapeutic in the most recent line of prior therapy

Must have a potential source of autologous T cells potentially sufficient to manufacture RAPA-201 cells, as defined by a circulating absolute lymphocyte count (ALC) of ≥ 300 cells/μL

Must not have

NYHA class III/IV congestive heart failure

Other active malignancy (except non-melanoma skin cancer)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up one (1) year after the last dose of rapa-201 cells.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment using RAPA-201 cells for patients with advanced solid tumors that have not responded to previous treatments. These reprogrammed immune cells are designed to survive better in tumors and attack cancer cells more effectively. The study aims to see if this new approach can help control tumor growth in these patients.

Who is the study for?

This trial is for adults with advanced solid tumors that have not responded to prior treatments including anti-PD-(L)1 therapy. Participants must be in relatively good health, with a performance status of ≤ 2 and adequate organ function. They should not have central nervous system metastasis or other active cancers, and must agree to use contraception if applicable.

What is being tested?

The study tests RAPA-201 T cell therapy combined with standard chemotherapy (carboplatin + paclitaxel). It's designed for patients whose tumors didn't respond to checkpoint inhibitor therapies. The goal is to see if this new treatment can shrink the tumors in patients who've already tried other treatments.

What are the potential side effects?

Potential side effects include typical chemotherapy-related issues like fatigue, nausea, low blood counts leading to increased infection risk, as well as possible immune-related reactions from the novel T cell therapy which could affect different organs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I was treated with an anti-PD-(L)1 drug in my last treatment.

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My blood has enough lymphocytes to make a specific cancer treatment.

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My heart pumps well, with an ejection fraction of 40% or higher.

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I do not have a history of unusual bleeding.

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My kidneys are functioning well.

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My cancer has returned or spread and cannot be removed by surgery after at least one treatment.

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My solid tumor is treatable with carboplatin and paclitaxel before T cell therapy.

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My cancer did not respond or came back within a year after treatment with an anti-PD-(L)1 drug.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe heart failure.

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I do not have any active cancer except for non-melanoma skin cancer.

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I am of childbearing age and not willing to use birth control.

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My brain metastasis has been treated.

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My high blood pressure is not under control.

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I have not had a stroke in the last 6 months.

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I have uncontrolled chest pain due to heart disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ one (1) year after the last dose of rapa-201 cells.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~one (1) year after the last dose of rapa-201 cells.

This trial's timeline: 3 weeks for screening, Varies for treatment, and one (1) year after the last dose of rapa-201 cells. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety of RAPA-201 Cell Therapy

Secondary study objectives

Overall Response Rate

Progression Free Survival (PFS) and Overall Survival (OS)

Quality of Life (QOL)

Other study objectives

T Cell Immune Reconstitution

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Administration of RAPA-201 cellsExperimental Treatment2 Interventions

RAPA-201 cells will be administered at a target flat dose of 400 x 10\^6 cells per infusion.

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for esophageal cancer include mTOR inhibitors, immune checkpoint inhibitors, and adoptive T cell therapies. mTOR inhibitors like temsirolimus work by blocking the mTOR pathway, which is crucial for cancer cell growth and proliferation, thereby slowing tumor progression. Immune checkpoint inhibitors, such as those targeting PD-1/PD-L1, enhance the immune system's ability to recognize and attack cancer cells by preventing the 'off' signals that tumors use to evade immune detection. Adoptive T cell therapies, like the RAPA-201 cells, involve reprogramming a patient's own T cells to be more effective against cancer. These cells are engineered to resist immunosuppressive signals within the tumor microenvironment and are polarized to a Th1/Tc1 phenotype, which is more effective in killing cancer cells. These mechanisms are significant for esophageal cancer patients as they offer targeted approaches that can potentially improve survival and reduce tumor burden, especially in cases where traditional therapies have failed.

Antiproliferative effect of a novel mTOR inhibitor temsirolimus contributes to the prolonged survival of orthotopic esophageal cancer-bearing mice.