Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Neoplasm Metastasis

Uterine Cervical Neoplasms

Vaginal Neoplasms

Vulvar Neoplasms

Anus Neoplasms

Carcinoma, Adenosquamous

Squamous Cell Carcinoma of Head and Neck

Oropharyngeal Neoplasms

Penile Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Head and Neck Neoplasms

Vaginal Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Genital Neoplasms, Male

Genital Diseases, Male

Penile Diseases

Male Urogenital Diseases

Vulvar Diseases

Vaginal Cancer

Penile Cancer

Anal Cancer

Vulvar Cancer

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunomodulating Agents

Subjects will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin.

Participants will receive a conditioning regimen (cyclophosphamide and fludarabine), E7 TCR-T cells as a single infusion, and adjuvant high-dose aldesleukin.

E7 TCR-T cells

Carrie Snyder

Christian Hinrichs, MD

This is a phase II clinical trial to assess the clinical activity of immunotherapy with E7 TCR-T cells for metastatic HPV-associated cancers. HPV-associated cancers in include cervical, throat, penile, vulvar, vaginal, anal, and other cancers. Participants will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin. Clinical response to treatment will be determined.

This study will determine the tumor response rate for the treatment of HPV-associated cancers with E7 TCR-T cells. E7 TCR-T cells are autologous gene-engineered T cells that target HPV16 E7 through a T cell receptor (TCR). E7 is an HPV oncoprotein that is present in HPV-associated cancers. Participants must have the HLA-A\*02:01 allele, which is required for tumor targeting by the E7 TCR. Treatment consists of a conditioning regimen (cyclophosphamide and fludarabine), a single infusion of E7 TCR-T cells, and adjuvant aldesleukin. Tumor response rate and response duration will be determined. Safety data will also be collected.

This is a single-arm phase II clinical trial.

E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers

A Phase II Trial of T Cell Receptor Gene Therapy Targeting Human Papillomavirus ( HPV) 16 E7 for HPV-Associated Cancers

Primary and secondary endpoint data will be shared.

Objective tumor response as measured by RECIST

Christian Hinrichs

Chief, Section of Cancer Immunotherapy

Recurrence

Carcinoma, Hepatocellular

Liver Neoplasms

Liver Diseases

The number of TIL is decided by dose escalation experiment.

Tumor infiltrating lymphocytes were isolated from tumor tissues from tumor biopsy or operation. These TILs were cultured in human IL-2 medium for 4 to 5 weeks. 10e9 to 10e10 TILs were yielded. The phenotype, function and sterile were detected before these TILs infused patients.

Tumor infiltrating lymphocyte

Early clinical trials on evaluating the tolerance, safety and efficacy of autologous TILs in high-risk recurrent primary hepatocellular carcinoma

A Clinical Study in Patients With High-risk Recurrent Primary Hepatocellular Carcinoma Using Autologous TILs

Early Clinical Trials on Evaluating the Tolerance, Safety and Efficacy of Autologous TILs in High-risk Recurrent Primary Hepatocellular Carcinoma

To evaluate the tolerability and safty of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.

To evaluate the efficacy of autologous TILs in high-risk recurrent primary hepatocellular carcinoma.

Eastern Hepatobiliary Surgery Hospital

CAR-T (Shanghai) Cell Biotechnology Co., Ltd.

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Lung Neoplasms

Vaccines

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Non-myeloablative, lymphocyte depleting preparative regimen, followed by KK-LC-1 TCR T cells plus aldesleukin at escalating doses

dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15 minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses).

IL-2 (Aldesleukin)

30 mg/kg IV infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5)

KK-LC-1 TCR

25 mg/m2 IV infusion over 30 minutes (+ 10 min) To be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2)

Monica E Epstein, R.N.

Scott M Norberg, D.O.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

Researchers have found a new way to treat cancer using T cell therapy. The therapy used in this study is T Cell Receptor (TCR) Gene Therapy Targeting KK-LC-1, a cancer germline antigen that is expressed by certain cancers. This therapy is a type of treatment in which a participant s T cells (a type of immune system white blood cell) are changed in the laboratory to attack cancer cells and given back to the participant. This treatment might help people with KK-LC-1 positive cancers which may include gastric, breast, cervical, lung and other epithelial Cancers. Epithelial cancers are cancers that begin in the cells that line an organ.

Objective:

The purpose of this study is to determine the safety of different doses of KK-LC-1 TCR T cells plus aldesleukin to treat metastatic or refractory/recurrent KK-LC-1 positive cancers.

Eligibility:

Adults aged 18 and older with metastatic or refractory/recurrent KK-LC-1 positive epithelial cancer.

Design:

Participants will be screened with HLA typing (a blood test needed for eligibility) and KK-LC-1 testing of the cancer tumor (to determine if the cancer is KK-LC-1 positive). A new biopsy may be needed if tumor from an outside location is not available for KK-LC-1 testing. Eligible participants will come to the NIH campus to have a screening evaluation which will include physical exam, review of medical history and current medications, blood and heart tests, imaging (X-ray, CT scan, MRI or PET scan), and evaluation of participant s veins that are used for drawing blood.

If the participant is eligible for the study based on the screening evaluation, they will have a baseline evaluation prior to receiving the experimental treatment which may include additional laboratory or imaging tests.

Participants will have a large IV catheter inserted into a vein to undergo a procedure called leukapheresis. Leukapheresis is the removal of the blood by a machine to collect specific white blood cells. The remaining blood is returned to the body. This procedure is needed to collect the cells that will be modified to target the cancer. The cells are grown in the lab and given back to the participant through an injection into the participant's tumor. It takes 11-15 days to grow the cells.

While the cells are growing, the participant will be admitted to the hospital about one week

before the cell infusion to receive 2 types of chemotherapy through an IV catheter over 5 days. The main purpose of the chemotherapy is to make the cells more effective in fighting the cancer tumors. The cells will be given 1-2 days after the last dose of chemotherapy. Within 24 hours after the cell infusion, participants will be given a cell growth factor called aldesleukin through an IV for up to 4 days. Aldesleukin is thought to help the cells live longer in the participant s body. Participants will recover in the hospital until they are well enough to go home, which is usually about 7-12 days after the cell infusion or last dose of aldesleukin.

Participants will have a follow-up visit at approximately 40 days after the date of cell infusion. This visit will be to evaluate the safety of the cell therapy and the response of the cancer to the treatment which will include physical examination, lab tests, and imaging studies. If a participant has stable disease or their cancer has responded to the treatment, they will be seen again at 12 weeks post cell infusion, every 3 months x 3 visits, and then every 6 months x 5 years. If a participant s cancer progresses after this therapy, they will be return to their home doctor for further management.

After receiving cell therapy, participants will be followed on a long-term gene therapy protocol. Participants will have blood drawn periodically to test if the cells have grown or changed. These blood tests will take place immediately before the cells, and then at 3, 6, and 12 months for the first year and possibly annually thereafter based on the results. These tests can be drawn locally and sent to the NIH. After a participant is off the study, they will be contacted by telephone or mailed questionnaire for a total of 15 years after cell therapy....

Background:

KK-LC-1 is a cancer germline (CG) antigen with expression restricted to germ cells (which lack MHC class I expression) in adults and epithelial cancers including lung, breast and gastric.

This limited expression pattern makes it an ideal target for T Cell Receptor (TCR) gene therapy.

TCR T cell therapy targeting CG antigens has been shown to induce objective responses without autoimmunity or off-target toxicity in participants with melanoma, synovial sarcoma and cervical cancer

T cells genetically engineered with a TCR targeting KK-LC-1 display specific reactivity against HLA-A01:01, KK-LC-1 target cells.

KK-LC-1 TCR T cells can mediate tumor regression in pre-clinical mouse models of cancer

Objective:

To determine the maximally tolerated dose of KK-LC-1 TCR T cells plus aldesleukin for the treatment of metastatic KK-LC-1 positive epithelial cancers.

Eligibility:

Participants greater than or equal to 18 years old with metastatic or refractory/recurrent KK-LC-1 positive epithelial cancer.

Prior first line systemic therapy is required unless the participant declines standard treatment.

Participants must be HLA-A-01:01-positive.

Design:

This is a phase I clinical trial that will test the safety and efficacy of escalating doses of KK-LC-1 TCR T cells.

Participants will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of KK-LC-1 TCR T cells and high-dose aldesleukin.

Re-treatment will be allowed for a small number of subjects

T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers

A Phase I Trial of T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers

.IPD recorded in the medical record will be shared with intramural investigators upon request.

The fraction of patients who experience a DLT will be identified at a given dose level, with information reported about the number and grade of each type of DLT identified.

National Cancer Institute (NCI)

Carcinoma, Non-Small-Cell Lung

Melanoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Colonic Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy

LYL845 is an autologous tumor infiltrating lymphocyte (TIL) enhanced via Epi-R, a proprietary epigenetic reprogramming technology

LYL845

Lauren Levine, MD

Laura Molnar

Naseem Esteghamat, MD

J. Randolph Hecht, MD

Chris Hannigan

Michael Hurwitz, MD, PhD

Jialing Zhang

Geoffrey Gibney, MD

Stephanie Wagner

Asad Javed, MD

Donald Lawrence, MD

Jordan Weiss

Elizabeth Buchbinder, MD

Martin Gutierrez, MD

Celina Joco

Sarah Weiss

Xiaoru Chen

Brent Hanks, MD

CCI Clinical Trials Office

Cara Dauch

Joal Beane, MD

Clinical Trials Line

Robert Eil

Yazan Samhouri, MD

Sanjay Chandrasekaran, MD

John Hyngstrom, MD

Kaitlin Stephens

Fred Hutch Intake

This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).

This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). During the dose-escalation phase of the study (Part A), participants with melanoma will be enrolled. Once a safe recommended Phase 2 dose range (RP2DR) has been established in Part A, enrollment will be expanded (Part B) to include additional participants with melanoma, NSCLC and CRC.

Single-arm, open-label, dose-escalation and -expansion study

A Study to Investigate LYL845 in Adults With Solid Tumors

A Phase 1 Study to Assess the Safety and Efficacy of LYL845 in Adults With Relapsed and/or Refractory Metastatic or Locally Advanced Melanoma and Selected Solid Tumor Malignancies

Evaluate incidence of dose-limiting toxicities (DLTs)

Evaluate incidence of treatment-emergent adverse events (TEAEs)

Evaluate severity of treatment-emergent adverse events (TEAEs)

Determine the recommended Phase 2 dose range (during dose-escalation phase)

Evaluate anti-tumor activity of LYL845 based on overall response rate (ORR) by RECIST, version 1.1

Lyell Immunopharma, Inc.

Melanoma, Cutaneous Malignant

Ocular Melanoma

Intraocular Melanoma

Pembrolizumab

Oxaliplatin

Irinotecan

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC.

Patients with advanced, metastatic colorectal adenocarcinoma who have failed or are intolerant to at least one line of therapy that included either irinotecan or oxaliplatin.

Patients with advanced, metastatic uveal melanoma.

Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor.

Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers	NCT05686226	Cervical Cancer Throat Cancer Oropharynx Canc... Anal Cancer Vulva Cancer Vaginal Cancer Penile Cancer Metastatic Canc... HPV-Related Mal... HPV-Related Car... HPV-Related Cer... HPV-Related Squ... HPV-Related Ade... HPV Positive Or... HPV-Associated ... HPV-Related Ade... HPV-Related End... HPV-Related Ana... HPV-Related Pen... HPV-Related Vul... HPV Positive Re...	E7 TCR-T cells	18 Years -	Rutgers, The State University of New Jersey
A Clinical Study in Patients With High-risk Recurrent Primary Hepatocellular Carcinoma Using Autologous TILs	NCT04538313	Hepatic Carcino...	Tumor infiltrat...	18 Years -	CAR-T (Shanghai) Cell Biotechnology Co., Ltd.
T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers	NCT05035407	Kita-kyushu Lun...	IL-2 (Aldesleuk... Cyclophosphamid... KK-LC-1 TCR Fludarabine	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
A Study to Investigate LYL845 in Adults With Solid Tumors	NCT05573035	Melanoma Non-small Cell ... Colorectal Canc...	LYL845	18 Years - 75 Years	Lyell Immunopharma, Inc.
A Study of TBio-4101 (TIL) and Pembrolizumab in Patients With Advanced Solid Tumors	NCT05576077	Breast Cancer Colorectal Canc... Uveal Melanoma Cutaneous Melan... Non-Small Cell ... Head and Neck S...	TBio-4101 Pembrolizumab	18 Years - 70 Years	Turnstone Biologics, Corp.
A Study of DeTIL-0255 in Adults With Advanced Malignancies	NCT05107739	Platinum-resist... Endometrial Can... Cervical Cancer	Drug Product De...	18 Years - 70 Years	Nurix Therapeutics, Inc.
A Study to Investigate LYL845 in Adults With Solid Tumors	NCT05573035	Melanoma Non-small Cell ... Colorectal Canc...	LYL845	18 Years - 75 Years	Lyell Immunopharma, Inc.
Study on TIL for the Treatment of Advanced Hepatobiliary-Pancreatic Cancers	NCT05098197	Advanced Liver ... Tumor Infiltrat... Treatment Side ... Effects of Immu... Advanced Pancre...	Tumor Infiltrat...	18 Years - 75 Years	Shanghai Juncell Therapeutics

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