Actively Recruiting

Phase 2
Age: 18Years - 72Years
All Genders
NCT03412877

Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer

Led by National Cancer Institute (NCI) · Updated on 2026-05-08

285

Participants Needed

1

Research Sites

498 weeks

Total Duration

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AI-Summary

What this Trial Is About

Background: A person s tumor is studied for mutations. When cells are found that can attack the mutation in a person s tumor, the genes from those cells are studied to find the parts that make the attack possible. White blood cells are then taken from the person s body, and the gene transfer occurs in a laboratory. A type of virus is used to transfer the genes that make those white blood cells able to attack the mutation in the tumor. The gene transfer therapy is the return of those white blood cells back to the person. Objective: To see if gene transfer therapy of white blood cells can shrink tumors. Eligibility: People with certain metastatic cancer for which standard treatments have not worked. Design: Participants may complete screening under another protocol. Screening includes: * Getting tumor cells from a previous procedure * Medical history * Physical exam * Scans * Blood, urine, heart, and lung tests The study has 8 stages: 1. Screening tests repeated over 1-2 weeks. Participants will have leukapheresis: Blood is removed by a needle in one arm. A machine removes white blood cells. The rest of the blood is returned by a needle in the other arm. 2. Care at home over approximately 12 weeks. 3. Stopping therapy for 4-6 weeks while their cells are changed in a lab. 4. Hospital stay approximately 3-4 weeks for treatment. An IV catheter will be placed in the chest to administer drugs. 5. Patients on Arm 2 of the study will receive the first dose of pembrolizumab while in the hospital. Three additional doses will be given after the cell infusion 3 weeks apart. 6. Receiving changed cells by catheter. Then getting a drug over 1-5 days to help the cells live longer. 7. Recover in the hospital for 1-2 weeks. Participants will get drugs and have blood and urine tests. 8. Participants will take an antibiotic and maybe an antiviral for at least 6 months after treatment. They will have repeat screening tests at visits every few months for the first year, every 6 months for the second year, then as determined.

CONDITIONS

Official Title

Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer

Who Can Participate

Age: 18Years - 72Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 18 and 72 years
  • Metastatic solid cancer measurable and in one of five cohorts: gastrointestinal/genitourinary; breast, ovarian, and other solid cancers; non-small cell lung cancer; endocrine/neuroendocrine tumors; multiple myeloma with measurable solid tumors
  • Documented cancer diagnosis
  • Cancer refractory to approved standard systemic therapies per cohort-specific treatments
  • Three or fewer asymptomatic brain metastases less than 1 cm or stable treated brain lesions
  • Clinical performance status of ECOG 0 or 1
  • Willingness to use birth control during and after treatment if of child-bearing potential
  • Negative pregnancy test if applicable
  • Seronegative for HIV, hepatitis B antigen, and hepatitis C antibody (with additional testing if hepatitis C antibody positive)
  • Adequate blood counts and organ function within specified limits
  • Completed prior systemic therapy at enrollment
  • Ability to understand and sign informed consent and durable power of attorney
  • Co-enrollment on protocol 03-C-0277
Not Eligible

You will not qualify if you...

  • Pregnant or nursing
  • Concurrent systemic steroid therapy
  • Active systemic infections or major uncompensated medical illnesses
  • Major bronchial occlusion or bleeding not treatable for non-small cell lung cancer cohort
  • Primary immunodeficiency disorders
  • History of major organ autoimmune disease
  • For Arm 2: Grade 3 or 4 major organ immune-related adverse events from prior PD-1/PD-L1 treatment
  • Opportunistic infections
  • Severe hypersensitivity to cyclophosphamide, fludarabine, or aldesleukin
  • Medical history compromising ability to tolerate high-dose aldesleukin (except low-dose allowed for some)
  • History of coronary revascularization or ischemic symptoms
  • Reduced heart function (LVEF ≤ 45%) or lung function (FEV1 ≤ 50%) if clinically indicated
  • Use of other investigational agents

AI-Screening

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Trial Site Locations

Total: 1 location

1

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

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Research Team

N

NCI SB Immunotherapy Recruitment Center

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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