Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Prostatic Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Carcinoma, Transitional Cell

Ovarian Cancer

Ovarian Epithelial Cancer

Transitional Cell Carcinoma

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Analgesics

Antibodies

Antibodies, Monoclonal

Aldesleukin

Immunomodulating Agents

Nivolumab

Immunoglobulins

Interleukin-2

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Single dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses.

Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days.

The investigational agent in this protocol is NeoTCR P1, an autologous adoptive T cell therapy (ACT) for patients with solid cancer. NeoTCR P1 is composed of apheresis derived CD8 and CD4 T cells that are precision genome engineered to express one autologous TCR of native sequence that targets a neoepitope (neoE) presented by human leukocyte antigen (HLA) receptors exclusively on the surface of that patient's tumor cells and not on other cells in the body.

NeoTCR-P1 adoptive cell therapy

Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody

nivolumab

IL-2 is a biologic response modifier. It is a type of protein called a cytokine.

IL-2

This is a first in human, single arm, open label, Phase 1a/1b study to determine the safety, feasibility, and efficacy of a single dose of NeoTCR-P1 T cells in participants with solid tumors.

A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors

A Phase 1a/1b, Open-label First-in-human Study of the Safety, Tolerability and Feasibility of Gene-edited Autologous NeoTCR-T Cells (NeoTCR-P1) Administered as a Single Agent or in Combination With Anti-PD-1 to Patients With Locally Advanced or Metastatic Solid Tumors

Dose limiting toxicity (DLT) is defined as protocol-defined adverse events that occur within 28 days following infusion of Neo-TCR-P1 administered as a single agent without or with IL-2, or in combination with nivolumab.

Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Cytokine release syndrome (CRS) and neurotoxicity associated with NeoTCR-P1 will be graded according to ASBMT consensus grading.

The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level.

Percent of screened patients that enroll on study and receive NeoTCR-P1

ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator

Duration of response, defined as time from the first occurrence of a documented objective response to the time of relapse or death from any cause

PFS is defined from date of administration of NeoTCR-P1 cell infusion to the date of disease progression per the RECIST v1.1 or death as a result of any cause. Subjects who do not meet criteria for progression by the analysis data cut-off date will be censored at their last evaluable disease assessment date

OS will be measured from the date of administration of NeoTCR-P1 to the date of death. Subjects who have not died by the analysis data cut-off date will be censored at their last date of contact.

PACT Pharma, Inc.

Digestive System Diseases

Adenocarcinoma

Pancreatic Neoplasms

Cholangiocarcinoma

Adenocarcinoma of Lung

Endometrial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Pancreatic Cancer

Bile Duct Cancer

Lung Adenocarcinoma

Phase I: Dose-escalation of TCR-T Cell Drug Product

Phase II: Single dose of TCR-T Cell Drug Product after MTD/RP2D determine in Phase I portion of the study

Phase I: Dose-escalation of TCR-T Cell Drug Product with Aldesleukin (IL-2)

Phase II: Single dose of TCR-T Cell Drug Product with Aldesleukin (IL-2) after MTD/RP2D determine in Phase I portion of the study

Phase I:

Ascending dose, single Infusion of TCR+ Cells

Phase II:

Single infusion at the RP2D

Neoantigen specific TCR-T cell drug product

To support growth and activation of TCR-T cell drug product

Aldesleukin (IL-2)

Scott Kopetz, MD, PhD

A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors

A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors.

An HLA Typing and Tumor Neoantigen Mutation Testing Protocol (Protocol # TCR001-002) has been used to identify patients for potential enrollment into this Study Protocol. Subjects who have completed the HLA Typing and Tumor Neoantigen Mutation Testing Protocol, i.e., subjects for whom a TCR matching the subject's somatic mutation(s) and HLA type restriction combination is available in Alaunos' TCR library will be eligible for enrollment on this study.

The Phase I part of this study is a prospective, open-label, dose-escalation study of TCR-T cell drug product in patients with progressive or recurrent solid tumors who have failed standard therapy. The Phase II part is a prospective, open-label, single dose portion of the study. The Phase II part will begin once the MTD/RP2D in the Phase I part has been determined.

Subjects with one of the following histologically confirmed solid tumors will be included:

* Cohort 1: Gynecologic cancer (e.g., ovarian, endometrial)
* Cohort 2: Colorectal cancer
* Cohort 3: Pancreatic cancer
* Cohort 4: Non-small cell lung cancer (NSCLC); NSCLC includes but is not limited to squamous cell carcinoma, adenosquamous carcinoma or adenocarcinomas
* Cohort 5: Cholangiocarcinoma

Subject must have a tumor mutation and HLA typing combination that matches to at least one of the following TCRs in the Alaunos' library (mutation \& HLA type):

* KRAS G12D \& HLA-A\*11:01
* KRAS G12D \& HLA-C\*08:02
* KRAS G12V \& HLA-A\*11:01
* KRAS G12V \& HLA-C\*01:02
* TP53 R175H \& HLA-A\*02:01
* TP53 R175H \& HLA-DRB1\*13:01
* TP53 R248W \& HLA-A\*68:01
* TP53 Y220C \& HLA-A\*02:01
* TP53 Y220C \& HLA-DRB3\*02:02
* EGFR E746-A750del \& HLA-DPA1\*02:01, DPB1\*01:01

Phase I/II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors

Phase I/II Study of Autologous T Cells Engineered Using the Sleeping Beauty System to Express T-Cell Receptors (TCRs) Reactive Against Cancer-specific Mutations in Subjects With Solid Tumors

Determine the Objective response rate (ORR) per RECIST v1.1 and iRECIST

TCR-T cellular persistence in peripheral blood (e.g., Cmax, Tmax, AUCD0-D28, etc.) over time determined by VCN.

Insertion-site clonality of TCR-T cell drug product will be measured by tracking the transposon insertion-site(s) of gene-modified cells in peripheral blood samples.

Serum cytokine concentrations including, but not limited to IFN-γ, IL-6, TNF-α, GM-CSF, IL-2, IL-7, and IL-15 will be determined by multiplex immunoassay.

Immunogenicity elicited against the transgenic components of the TCR therapy (i.e., anti-drug antibody and T-cell responses) will be assessed by immunoassay of peripheral blood and serum samples.

Objective Response Rate (ORR) is defined as the proportion of FAS subjects achieving a confirmed PR or CR according to iRECIST during study.

The collection of tumor tissue samples is to enable the investigation of all T cells (T cell and TCR-T cell infiltration) in the tumor.

To evaluate the levels of blood-based tumor neoantigen biomarkers, peripheral blood samples collected from all subjects according to the schedule shown in may be analyzed.

An estimate of the ORR is determined by the proportion of confirmed objective responses and will be summarized separately for each of the tumor type subgroup.

Arm A: To define the incidence of DLT and the MTD of TCR-T cell drug product delivered as a single administration.

Arm B: To determine the MTD/MAD/RP2D of TCR-T cell drug product delivered as a single administration followed by IL-2 administration.

Objective Response Rate (ORR) is defined as the proportion of FAS subjects achieving a confirmed PR or CR according to RECIST v1.1 during study.

Treatment-emergent AEs through 28 days after last protocol therapy will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) Version 13.1 (or higher) System Organ Class and preferred term. The incidences and percentages of participants experiencing each AE preferred term will be summarized with descriptive statistics. AEs will also be summarized by NCI CTCAE, Version 5.0, by grade and by causality (attribution to study treatment).

The number of subjects who have undergone apheresis for TCR-T cell manufacturing and for whom the product was successfully released for infusion

Determine the TCR-T persistence, defined by the duration of TCR-T cell drug product measurable by vector copy number (VCN) in peripheral blood samples

Alaunos Therapeutics

Uterine Cervical Neoplasms

Uterine Cervical Diseases

Bor-Ching Sheu, MD, PhD

In this study proposal, the investigators will extend their previous studies and examine the kinetic cytotoxic activity with concordant expression of inhibitory natural killer (NK) receptors (iNKR) on activated T cells. The inhibitory role of cytokines will be defined by utilizing the investigators' previously established models of mixed lymphocytes and tumor cells coculture to analyze the expression and activity of cytokines involved in the regulation of iNKRs on cancer-encountered T cells.

In our extended studies, we have directly examined the expressions of various inhibitory natural killer cell Receptors (iNKRs) on Tumor-infiltrating lymphocytes (TILs) derived from human Cervical cancer (CC) by triple-color flow cytometry with combination of different surface markers. We found up-regulated expression of certain iNKRs (CD94/NKG2A) in TILs and in mixed lymphocyte-cancer cell cocultures. In our previous studies, we demonstrated that certain cytokines, including IL-10, TGF-beta (Sheu et al, Journal of Immunology, 2001, 167:2972-2978), and IL-15 (Sheu et al, Cancer Research, 2005, 65:2921-2929) can be expressed by CC cells. We further demonstrated that activated T cells bear iNKRs which inhibit cytotoxic activity. iNKRs are proposed to restrain the T cell receptor (TCR)-mediated cytolysis. We found that CC cells had altered HLA-A, -B, and -C molecules in a cancer microenvironment. The acquisition of both NK-like activity and expression of iNKRs by these T cells is parallel to prevent damage to normal host cells. However, there is also limited knowledge about the regulatory role of iNKR expression in T cell cytotoxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors	NCT03970382	Solid Tumor	NeoTCR-P1 adopt... nivolumab IL-2	18 Years -	PACT Pharma, Inc.
Phase I/II Study of Autologous T Cells to Express T-Cell Receptors (TCRs) in Subjects With Solid Tumors	NCT05194735	Gynecologic Can... Colorectal Canc... Pancreatic Canc... Non-small Cell ... Cholangiocarcin... Ovarian Cancer Endometrial Can... Ovarian Carcino... Ovary Neoplasm Squamous Cell L... Adenocarcinoma ... Adenosquamous C...	Neoantigen spec... Aldesleukin (IL...	18 Years -	Alaunos Therapeutics
Cytokine Regulation of Natural Killer Receptors in Inhibiting Activated T Cell Function	NCT00173290	Cervical Cancer Breast Cancer Endometrial Can... Cancer		18 Years - 50 Years	National Taiwan University Hospital
Cytokine Regulation of Natural Killer Receptors in Inhibiting Activated T Cell Function	NCT00173290	Cervical Cancer Breast Cancer Endometrial Can... Cancer		18 Years - 50 Years	National Taiwan University Hospital

Spots Global Cancer Trial Database for t lymphocyte

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