NCT01567891

CT Antigen TCR-redirected T Cells for Ovarian Cancer.

Completed Phase 1, PHASE2 Results posted Last updated 27 June 2019

What this trial tests

Phase 1, PHASE2 trial testing NYESO-1c259 T cells in Ovarian Cancer in 9 participants. Completed in 6 June 2017.

Timeline

9 July 2013

Primary endpoint
6 June 2017

6 June 2017

Quick facts

Lead sponsor	Adaptimmune
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	9
Start date	9 July 2013
Primary completion	6 June 2017
Estimated completion	6 June 2017
Sites	5 locations across United States

Drugs / interventions tested

• NYESO-1c259 T cells — full drug profile →

Conditions studied

• Ovarian Cancer — all drugs for Ovarian Cancer →

Sponsor

Adaptimmune — full company profile →

Who can join

18 and older, any sex, with Ovarian Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Adverse Events Related to Study Treatment Primary · Up to 12 months

Number of Participants with Adverse Events related to study treatment

Group	Value	95% CI
NY-ESO-1ᶜ²⁵⁹T	5

Tumor Response Secondary · Change from baseline, every 4 weeks until month 3 and then every 3 month until disease progression

Number of participants with response as assessed by Immune-related Response Criteria (irRC)

Group	Value	95% CI
NY-ESO-1ᶜ²⁵⁹T	0

Peak Persistence of Modified T-cells in the Peripheral Blood Secondary · Days: 1, 2-4, weeks 1 to 4, Week 8, 12 and Month 6, then every 3 months thereafter until progression then during LTFU

Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood

Group	Value	95% CI
NY-ESO-1ᶜ²⁵⁹T	85862.6	27,310 – 169,753

Determine Functional Properties and Phenotype of Modified T-cells From Peripheral Blood. Secondary · Weeks 4 and 8 post T-cell infusion

Percentage of CD4+pentamer+ or CD8+pentamer+ cells expressing LAG-3, PD-1, TIM-3 in the functionality of NY-ESO-1ᶜ²⁵⁹T cells in the manufactured product and post-treatment blood.

%LAG-3

Group	Value	95% CI
Manufactured Product -Mean % CD4+Pentamer+	4
Week 4 Post-treatment- Mean % CD4+Pentamer+	3
Week 8 Post-treatment - Mean % CD4+Pentamer+	0
Manufactured Product - Mean % CD8+Pentamer+	3
Week 4 Post-treatment - Mean % CD8+Pentamer+	0
Week 8 Post-treatment - Mean % CD8+Pentamer+	0

%PD-1

Group	Value	95% CI
Manufactured Product -Mean % CD4+Pentamer+	6
Week 4 Post-treatment- Mean % CD4+Pentamer+	0
Week 8 Post-treatment - Mean % CD4+Pentamer+	3
Manufactured Product - Mean % CD8+Pentamer+	1
Week 4 Post-treatment - Mean % CD8+Pentamer+	1
Week 8 Post-treatment - Mean % CD8+Pentamer+	4

%TIM-3

Group	Value	95% CI
Manufactured Product -Mean % CD4+Pentamer+	97
Week 4 Post-treatment- Mean % CD4+Pentamer+	17
Week 8 Post-treatment - Mean % CD4+Pentamer+	11
Manufactured Product - Mean % CD8+Pentamer+	97
Week 4 Post-treatment - Mean % CD8+Pentamer+	24
Week 8 Post-treatment - Mean % CD8+Pentamer+	7

Correlate NY-ESO-1 Expression in Tumor Tissue Before Treatment With Archival Tumor Tissue to Assess Impact of Therapy on Expression of NY-ESO-1 Protein Secondary · Screening and at Baseline

NY-ESO-1 expression as determined by Histoscore (H score). Histoscore (0-300) represents the amount of NY-ESO-1 protein present in the tissue sample. H-Score formula: \[1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)\] (It is not clearly established if NY-ESO-1 H score has an association with prognosis.)

Screening/Archival

Group	Value	95% CI
Subject 1	50
Subject 2	100

Baseline

Group	Value	95% CI
Subject 1	15
Subject 2	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Start of lymphodepletion to end of intervention phase (up to 12 months post T-cell infusion). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

NY-ESO-1ᶜ²⁵⁹T

Serious: 5/6 (83%)

Deaths: 6/6

Serious adverse events (7 terms)

Reaction	System	NY-ESO-1ᶜ²⁵⁹T
Febrile neutropenia	Blood and lymphatic system disorders	—
Cytokine Release Syndrome	Immune system disorders	—
Dehydration	Metabolism and nutrition disorders	—
Disease Progression	General disorders	—
Pancytopenia	Blood and lymphatic system disorders	—
Presyncope	Nervous system disorders	—
Pyrexia	General disorders	—

Other adverse events (65 terms — click to expand)

Reaction	System	NY-ESO-1ᶜ²⁵⁹T
White blood cell count decreased	Investigations	—
Neutrophil count decreased	Investigations	—
Nausea	Gastrointestinal disorders	—
Abdominal Pain	Gastrointestinal disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Dry Skin	Skin and subcutaneous tissue disorders	—
Fatigue	General disorders	—
Alopecia	Skin and subcutaneous tissue disorders	—
Anemia	Blood and lymphatic system disorders	—
Ascites	Gastrointestinal disorders	—
Confusional state	Psychiatric disorders	—
Constipation	Gastrointestinal disorders	—
Diarrhea	Gastrointestinal disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Headache	Nervous system disorders	—
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	—
Pyrexia	General disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Sinus Tachycardia	Cardiac disorders	—
Alanine aminotransferase increased	Investigations	—
Anal incontinence	Gastrointestinal disorders	—
Anxiety	Psychiatric disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Asparate aminotransferase increased	Investigations	—
Back Pain	Musculoskeletal and connective tissue disorders	—
Blood alkaline phosphatase increased	Investigations	—
Blood creatinine increased	Investigations	—
Bone Pain	Musculoskeletal and connective tissue disorders	—
Chills	General disorders	—
Conjunctivitis	Immune system disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Dermatitis allergic	Skin and subcutaneous tissue disorders	—
Dizziness	Nervous system disorders	—
Facial Pain	General disorders	—
Hyperglycemia	Metabolism and nutrition disorders	—
Hypernatremia	Metabolism and nutrition disorders	—
Hypersensitivity	Immune system disorders	—
Hypokalemia	Metabolism and nutrition disorders	—
Hypomagnesemia	Metabolism and nutrition disorders	—
Hypotension	Vascular disorders	—

Most-reported serious reactions: Febrile neutropenia, Cytokine Release Syndrome, Dehydration, Disease Progression, Pancytopenia, Presyncope, Pyrexia.

Data from ClinicalTrials.gov NCT01567891 adverse events section.

Sponsor's own description

This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. These new T cells are called "engineered T cells" because the new gene is causing them to become directed toward the ovarian cancer cells rather than their usual targets. These are also called "gene-modified T cells". For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY-ESO-1". After putting this new gene in T cells (a procedure called "gene therapy") the investigators will grow the cells in the laboratory and give these cells back to subjects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. T cells in health and disease.
   Sun L, Su Y, Jiao A, Wang X, et al · · 2023 · cited 717× · PMID 37332039 · DOI 10.1038/s41392-023-01471-y
2. Advances in ovarian cancer therapy.
   Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. · · 2018 · cited 417× · PMID 29249039 · DOI 10.1007/s00280-017-3501-8
3. T cell receptor (TCR) signaling in health and disease.
   Shah K, Al-Haidari A, Sun J, Kazi JU. · · 2021 · cited 414× · PMID 34897277 · DOI 10.1038/s41392-021-00823-w
4. NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives.
   Thomas R, Al-Khadairi G, Roelands J, Hendrickx W, et al · · 2018 · cited 298× · PMID 29770138 · DOI 10.3389/fimmu.2018.00947
5. Immunotherapy in ovarian cancer.
   Odunsi K. · · 2017 · cited 292× · PMID 29232467 · DOI 10.1093/annonc/mdx444
6. Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant.
   Yang C, Xia BR, Zhang ZC, Zhang YJ, et al · · 2020 · cited 246× · PMID 33123161 · DOI 10.3389/fimmu.2020.577869
7. Driving gene-engineered T cell immunotherapy of cancer.
   Johnson LA, June CH. · · 2017 · cited 211× · PMID 28025979 · DOI 10.1038/cr.2016.154
8. Heterogeneity of the tumor immune microenvironment and its clinical relevance.
   Jia Q, Wang A, Yuan Y, Zhu B, et al · · 2022 · cited 176× · PMID 35461288 · DOI 10.1186/s40164-022-00277-y