What side effects are associated with this type of intervention?

Common side effects of cancer treatments similar to T-cell receptor gene-engineered T cells (TCR-T) targeting tumor-specific antigens with CD40 activation and PD-1 blockade include immune-related adverse events such as skin reactions (rash, pruritus), gastrointestinal issues (diarrhea, colitis), endocrine dysfunctions (thyroiditis, adrenal insufficiency), and pulmonary complications (pneumonitis). Patients may also experience fatigue, fever, and infusion-related reactions. Severe side effects, though less common, can include cytokine release syndrome and neurotoxicity.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for cancer treatment that are similar to the TCR-T trial. Notably, chimeric antigen receptor (CAR) T-cell therapies, such as axicabtagene ciloleucel and tisagenlecleucel, target specific antigens on cancer cells. Additionally, immune checkpoint inhibitors like pembrolizumab and nivolumab, which block PD-1, have been approved for various cancers. While CD40 activation is less commonly targeted, the combination of these approaches represents a promising area of cancer immunotherapy.

What other types of research exist?

Promising alternatives to TCR-T therapy for cancer patients include: 1) Dabrafenib and Trametinib for BRAF V600-mutant anaplastic thyroid cancer, 2) Larotrectinib and Entrectinib for TRK fusion-positive cancers, 3) Pembrolizumab and Nivolumab for PD-1/PD-L1 positive tumors, 4) Sipuleucel-T for castration-resistant prostate cancer, and 5) Combination therapies like lenvatinib/pembrolizumab for various advanced cancers. These therapies have shown efficacy in targeting specific genetic mutations and enhancing immune response against tumors.

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CAR T-cell Therapy

Personalized TCR-T Cell Therapy for Cancer

Phase 1

Waitlist Available

Led By Eric Tran, PhD

Research Sponsored by Providence Health & Services

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

Patients positive for hepatitis B core antibody (anti-HBc, total), are eligible only if HBV DNA is non-detectable by qPCR.

Must not have

Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, uncontrolled ischemic or severe valvular heart disease. Patients with a history of myocardial infarction, cerebral vascular accident, thrombosis or pulmonary embolus within 12 months prior to the first dose of study treatment are excluded from this study.

Active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

All Individual Drugs Already Approved

Summary

This trial tests a new treatment for patients with incurable cancers. It uses modified immune cells and two supportive drugs to help the immune system better target and attack cancer cells. The goal is to see if this approach is safe and effective.

Who is the study for?

This trial is for adults with advanced epithelial cancers deemed incurable, who have a life expectancy over 12 weeks and specific immune cells suitable for gene therapy. They must not be pregnant or planning pregnancy, agree to contraception, and have adequate organ function. Excluded are those with certain medical conditions, recent malignancies other than treated skin cancer or in situ carcinomas, severe heart disease, active infections like hepatitis B/C unless undetectable by qPCR, HIV-positive patients not on stable treatment, or anyone unable to follow the study protocol.

What is being tested?

The trial tests TCR-transduced T cells combined with CDX-1140 (a CD40 agonist) and Pembrolizumab (PD-1 blockade) in patients with incurable cancers. It's a phase I/Ib study starting with safety assessments followed by efficacy evaluations using Simon's Two-Stage design to determine if these treatments can safely enhance the body's immune response against cancer.

What are the potential side effects?

Potential side effects include reactions related to the infusion of engineered T-cells such as fever and chills; autoimmune-like symptoms due to increased immune activity; fatigue; possible organ inflammation from CDX-1140; and pembrolizumab may cause immune system-related side effects affecting various organs.

Eligibility Criteria

Inclusion Criteria

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

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

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I have hepatitis B but my viral load is undetectable.

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I have hepatitis C but my viral load is undetectable.

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I am 18 or older with advanced cancer that cannot be cured.

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My lab tests show I'm eligible for a specific gene therapy.

Exclusion Criteria

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

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I do not have severe heart problems or a history of heart attack or stroke in the last year.

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I do not have an active tuberculosis infection.

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I have or had lung inflammation not caused by an infection.

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I haven't taken any experimental cancer treatments or anti-CD40 therapy recently.

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I am on high doses of steroids for an autoimmune disease.

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I am able to follow the study's requirements and attend all follow-up visits.

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I had severe side effects from previous immunotherapy that required stopping the treatment or long-term steroids.

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I have had an organ or stem cell transplant.

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I have had cancer spread to the lining of my brain and spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events

Severity of adverse events

Secondary study objectives

Clinical benefit rate

Duration of response

Objective response rate

+1 more

Awards & Highlights

No Placebo-Only Group

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

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

1Treatment groups

Experimental Treatment

Group I: CDX-1140 + TCR-T + PembroExperimental Treatment3 Interventions

Patients will receive CDX-1440, TCR-T, and pembrolizumab.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

CDX-1140

2017

Completed Phase 2

~160

Pembrolizumab

FDA approved

0 / 14Eligibility 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 cancer treatments include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Chemotherapy uses drugs to kill rapidly dividing cells, while radiation therapy uses high-energy particles to destroy cancer cells. Targeted therapy focuses on specific molecules involved in cancer growth, and immunotherapy enhances the body's immune system to fight cancer. Treatments like T-cell receptor gene-engineered T cells (TCR-T) are a form of immunotherapy that involves modifying T cells to target tumor-specific antigens, activating CD40 to enhance immune response, and blocking PD-1 to prevent immune evasion by cancer cells. These mechanisms are crucial for cancer patients as they offer more precise and potentially effective treatment options, reducing damage to healthy cells and improving overall outcomes.

Propelling Immunotherapy Combinations Into the Clinic.