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Protocol Details

A Phase II Study Using the Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in Patients with Metastatic Cancer

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 72 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Gene Therapy;
Cell Therapy;
Adoptive Cell Therapy

Recruitment Keyword(s)



Endocrine Tumors;
Non-Small Cell Lung Cancer;
Ovarian Cancer;
Breast Cancer;
Gastrointestinal/Genitourinary Cancers;
Neuroendocrine Tumors;
Multiple Myeloma

Investigational Drug(s)

Individual Patient TCR-Transduced PBL

Investigational Device(s)



Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Aldesleukin
Biological/Vaccine: Individual Patient TCR-Transduced PBL
Drug: Pembrolizumab (KEYTRUDA )

Supporting Site

National Cancer Institute


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.


To see if gene transfer therapy of white blood cells can shrink tumors.


People with certain metastatic cancer for which standard treatments have not worked.


Participants may complete screening under another protocol. Screening includes:

-Getting tumor cells from a previous procedure

-Medical history

-Physical exam


-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.

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-Metastatic, solid cancer that can be measured, that falls into one of five cohorts: (1) gastrointestinal and genitourinary cancers; (2) breast, ovarian, and other solid cancers; (3) non-small cell lung cancer (NSCLC); (4) endocrine tumors including neuroendocrine tumors and, (5) multiple myeloma that includes measurable solid tumors (plasmacytomas). Participants with multiple myeloma are potentially eligible only if they have measurable multiple myeloma as defined in Section 16.7 after plasmacytoma resection.

Note: NSCLC includes but is not limited to squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinomas.

-Confirmation of diagnosis of cancer by the NCI Laboratory of Pathology.

-Refractory to approved standard systemic therapy. Specifically:

--Participants with metastatic colorectal cancer must have received oxaliplatin or irinotecan.

--Participants with breast and ovarian cancer must be refractory to both first- and second- line treatments.

--Participants with NSCLC must have received at least one platinum-based chemotherapy regimen and at least one FDA-approved targeted treatment (when appropriate).

-Participants with endocrine tumors including neuroendocrine tumors must be refractory to first-line therapy (e.g., lanreotide, octreotide) and must be refractory or have refused second-line treatments such as everolimus, sunitinib, or 177 Lu-Dotatate, if indicated.

-Participants with multiple myeloma must have received at least four prior lines of therapy that included at least one exposure to an immunomodulatory drug such as lenalidomide, a proteosome inhibitor, an anti-CD38 antibody treatment, and an autologous stem cell transplant.

-Participants with three (3) or fewer brain metastases that are < 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the participant to be eligible. Participants with surgically resected brain metastases are eligible.

-Age greater than or equal to 18 years and less than or equal to 72 years.

-Clinical performance status of ECOG 0 or 1.

-Participants of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.

-Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.


--Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

--Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.


-- ANC > 1000/mm^3 without the support of filgrastim

-- WBC greater than or equal to 2500/mm^3

-- Platelet count greater than or equal to 80,000/mm^3

--Hemoglobin > 8.0 g/dl. Subjects may be transfused to reach this cut-off.


--Serum ALT/AST less than or equal to 5.0 x ULN

--Serum creatinine less than or equal to 1.6 mg/dl.

--Total bilirubin less than or equal to 2.0 mg/dl, except in participants with Gilbert's Syndrome, who must have a total bilirubin less than or equal to 3.0 mg/dl.

-Participants must have completed any prior systemic therapy at the time of enrollment.

Note: Participants may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to grade 1 or less. In addition, participants with multiple myeloma may receive bridging therapy during the time between study enrollment and start of study therapy. This may be necessary due to the long time needed for cell production on this study. After bridging therapy and within 14 days of protocol treatment start, participants with multiple myeloma must still have measurable multiple myeloma.

-For Cohort 3: More than two weeks must have elapsed since any prior palliation for major bronchial occlusion or bleeding at the time the patient receives the preparative regimen, and patient s toxicities must have recovered to a grade 1 or less.

-Ability of subject to understand and the willingness to sign a written informed consent document.

-Willing to sign a durable power of attorney.

-Subjects must be co-enrolled on protocol 03-C-0277.


-Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

-Concurrent systemic steroid therapy.

-Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

-For Cohort 3: Any major bronchial occlusion or bleeding not amenable to palliation.

-Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).

-History of major organ autoimmune disease.

-For Arm 2: Grade 3 or 4 major organ irAEs following treatment with anti-PD-1/PD-L1, including but not limited to myocarditis and pneumonitis.

Note: Participants with grade 3 or 4 major organ irAEs may be enrolled on Arm 1 if all other eligibility criteria are met.

-Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)

-History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.

-For Cohorts 1, 2, or 4: Clinically significant participant history which in the judgment of the Principal Investigator (PI) would compromise the participants ability to tolerate high-dose aldesleukin.

Note: At the discretion of the PI, participants enrolled in Cohort 3 may receive low-dose aldesleukin.

-History of coronary revascularization or ischemic symptoms.

-For select participants with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.

-For select participants with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50% predicted.

-Participants who are receiving any other investigational agents.

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Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.

Lu YC, Yao X, Crystal JS, Li YF, El-Gamil M, Gross C, Davis L, Dudley ME, Yang JC, Samuels Y, Rosenberg SA, Robbins PF. Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions. Clin Cancer Res. 2014 Jul 1;20(13):3401-10. doi: 10.1158/1078-0432.CCR-14-0433.

Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, Lin JC, Teer JK, Cliften P, Tycksen E, Samuels Y, Rosenberg SA. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med. 2013 Jun;19(6):747-52. doi: 10.1038/nm.3161. Epub 2013 May 5.

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Principal Investigator

Referral Contact

For more information:

Steven A. Rosenberg, M.D.
National Cancer Institute (NCI)

NCI SB Immunotherapy Recruitment Center
National Cancer Institute (NCI)

(866) 820-4505

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
(866) 820-4505

Clinical Trials Number:


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