Trial Outcomes & Findings for Ticilimumab (CP-675,206) in Treating Patients With Stage IIIC or Stage IV Melanoma (NCT NCT00471887)
NCT ID: NCT00471887
Last Updated: 2020-10-26
Results Overview
Tumor infiltration of cluster of differentiation 4 and cluster of differentiation 8 (CD4+ and CD8+) cells (intratumoral and peritumoral) was assessed by immunohistochemistry of tumor tissue obtained through biopsy before and after administration of tremelimumab. Up to 10 randomly selected fields per sample were analyzed.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
pre treatment - post treatment at 24 months
Results posted on
2020-10-26
Participant Flow
Participant milestones
| Measure |
Treatment: CP-675,206 Monoclonal Antibody.
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Overall Study
STARTED
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32
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Overall Study
COMPLETED
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23
|
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Overall Study
NOT COMPLETED
|
9
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Reasons for withdrawal
| Measure |
Treatment: CP-675,206 Monoclonal Antibody.
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Overall Study
Adverse Event
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9
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Baseline Characteristics
Ticilimumab (CP-675,206) in Treating Patients With Stage IIIC or Stage IV Melanoma
Baseline characteristics by cohort
| Measure |
Treatment: CP-675,206 Monoclonal Antibody
n=32 Participants
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Age, Continuous
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52 years
n=5 Participants
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Sex: Female, Male
Female
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9 Participants
n=5 Participants
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Sex: Female, Male
Male
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23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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3 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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28 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
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Region of Enrollment
United States
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32 participants
n=5 Participants
|
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prior therapies
No Prior Therapy
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13 participants
n=5 Participants
|
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prior therapies
Biological Only
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4 participants
n=5 Participants
|
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prior therapies
Chemotherapy Based
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13 participants
n=5 Participants
|
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prior therapies
Other
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2 participants
n=5 Participants
|
|
Stage
IIIC
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4 participants
n=5 Participants
|
|
Stage
M1a
|
3 participants
n=5 Participants
|
|
Stage
M1b
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3 participants
n=5 Participants
|
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Stage
M1c
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22 participants
n=5 Participants
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PRIMARY outcome
Timeframe: pre treatment - post treatment at 24 monthsPopulation: 19 (4 Responders and 15 Non-responders) Outcome data summary: An increase in intratumoral infiltration of lymphocytes following administration of tremelimumab independent of clinical response is expected
Tumor infiltration of cluster of differentiation 4 and cluster of differentiation 8 (CD4+ and CD8+) cells (intratumoral and peritumoral) was assessed by immunohistochemistry of tumor tissue obtained through biopsy before and after administration of tremelimumab. Up to 10 randomly selected fields per sample were analyzed.
Outcome measures
| Measure |
Treatment: CP-675,206 Monoclonal Antibody
n=19 Participants
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Change in Tumor Infiltration by Cluster of Differentiation 8 (CD8) Positive Cytotoxic T Lymphocytes
Pre-Treatment (cell density)Intratumoral CD8+
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289 cells/mL
Standard Error 61
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Change in Tumor Infiltration by Cluster of Differentiation 8 (CD8) Positive Cytotoxic T Lymphocytes
Pre-Treatment (cell density)Intratumoral CD4+
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104 cells/mL
Standard Error 32
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Change in Tumor Infiltration by Cluster of Differentiation 8 (CD8) Positive Cytotoxic T Lymphocytes
Post-Treatment (cell density)Intratumoral CD8+
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955 cells/mL
Standard Error 191
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Change in Tumor Infiltration by Cluster of Differentiation 8 (CD8) Positive Cytotoxic T Lymphocytes
Post-Treatment (cell density)Intratumoral CD4+
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428 cells/mL
Standard Error 156
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SECONDARY outcome
Timeframe: pre treatment - post treatment at 24 monthsPopulation: 11 (3 Responders and 8 Non-responders)
HLA-DR is a surface marker of T cell activation after exposure to CTLA4 blocking antibodies. CD45RO is a maker of prior cognate antigen-exposed T cells. Together they mark cells with a surface phenotype of T effector or T effector memory cells. Ki67 is a marker of cell proliferation. The protein FOXP3 is involved in the regulation of the development and function of regulatory T cells, and serves as a marker of this cell type. Intratumoral expression of HLA-DR, CD45RO, Ki67 and FOXP3 was assessed by immunohistochemistry of tumor tissue obtained through biopsy before and after administration of tremelimumab.
Outcome measures
| Measure |
Treatment: CP-675,206 Monoclonal Antibody
n=11 Participants
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Change in Intratumoral Expression of the Proteins HLA-DR, CD45RO, Ki67 and FOXP3 and FOXP3"
HLA-DR/CD45RO
|
356.4 cells/mL
Standard Deviation 257.33
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Change in Intratumoral Expression of the Proteins HLA-DR, CD45RO, Ki67 and FOXP3 and FOXP3"
Ki67
|
-240.26 cells/mL
Standard Deviation 690.48
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Change in Intratumoral Expression of the Proteins HLA-DR, CD45RO, Ki67 and FOXP3 and FOXP3"
FOXP3
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132.15 cells/mL
Standard Deviation 160.35
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SECONDARY outcome
Timeframe: pre treatment - post treatment at 24 monthsPopulation: 21 (4 Responders and 17 Non-responders)
T cell receptor (TCR) usage was analyzed in genomic DNA from peripheral blood from patients before and after treatment with tremelimumab. High-throughput deep sequencing of the TCR Vβ CDR3 (Complementarity - determining region 3) region was analyzed to better characterize the expansion and clonality of the T cell repertoire. The frequency of circulating invariant natural killer T cells (iNKT) cell subsets were also characterized by flow cytometry in peripheral blood samples pre- and post-treatment. iNKT cells regulate the balance of Th1/Th2 immune responses.
Outcome measures
| Measure |
Treatment: CP-675,206 Monoclonal Antibody
n=21 Participants
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Differences in Morphological and Gene Expression Profiling Studies in Peripheral Blood Mononuclear Cells
CD4+iNKT pre-treatment
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104 cell density (number of cells/mm^2)
Standard Deviation 32
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Differences in Morphological and Gene Expression Profiling Studies in Peripheral Blood Mononuclear Cells
CD4+iNKT post-treatment
|
428 cell density (number of cells/mm^2)
Standard Deviation 156
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SECONDARY outcome
Timeframe: pre treatment - post treatment at 24 monthsPopulation: 21 (4 Responders and 17 Non-responders)
Th17 cells are CD4+ cells that are potent inducers of tissue inflammation and autoimmunity. The levels of this T cell subset were assessed in peripheral blood from patients before and after administration of tremelimumab. Th17 cells were assessed since the major dose limiting toxicities are inflammatory and autoimmune in nature. In addition, the phosphorylation of signaling molecules downstream of the TCR and cytokine receptors was evaluated in peripheral blood cells from patients before and after treatment with tremelimumab using intracellular flow cytometry. ab#cells = absolute number of cells
Outcome measures
| Measure |
Treatment: CP-675,206 Monoclonal Antibody
n=21 Participants
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Changes in the Protein Content in Peripheral Blood With an Increase in Proinflammatory Cytokines and Chemokines
Peripheral Blood Pre-treatment: pg/ml x 1E6cells
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73711 absolute number of cells
Interval 46912.0 to 100510.0
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Changes in the Protein Content in Peripheral Blood With an Increase in Proinflammatory Cytokines and Chemokines
Peripheral Blood Post-treatment: pg/ml x 1E6cells
|
101066 absolute number of cells
Interval 70644.0 to 131488.0
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Changes in the Protein Content in Peripheral Blood With an Increase in Proinflammatory Cytokines and Chemokines
Unstimulated CD4+Pre-Treatment
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0.46 absolute number of cells
Interval 0.22 to 0.7
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Changes in the Protein Content in Peripheral Blood With an Increase in Proinflammatory Cytokines and Chemokines
Unstimulated CD4+Post-Treatment
|
0.62 absolute number of cells
Interval 0.49 to 0.75
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SECONDARY outcome
Timeframe: pre treatment - post treatment at 24 monthsPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
Outcome measures
| Measure |
Treatment: CP-675,206 Monoclonal Antibody
n=31 Participants
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Overall Response (Complete or Partial Response) as Measured by RECIST Criteria
Progressive Disease
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27 participants
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Overall Response (Complete or Partial Response) as Measured by RECIST Criteria
Partial Response
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1 participants
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Overall Response (Complete or Partial Response) as Measured by RECIST Criteria
Complete Response
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3 participants
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SECONDARY outcome
Timeframe: pre treatment - post treatment at 24 monthsOutcome measures
| Measure |
Treatment: CP-675,206 Monoclonal Antibody
n=32 Participants
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Overall Safety Profile as Measured by NCI CTCAE v2.0
Seroius Adverse Event (SAE)SAE
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13 participants
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Overall Safety Profile as Measured by NCI CTCAE v2.0
Adverse Events (AE)
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13 participants
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Adverse Events
Treatment-CP-675,206
Serious events: 13 serious events
Other events: 13 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Treatment-CP-675,206
n=32 participants at risk
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Blood and lymphatic system disorders
Chronic Immune Thrombocytopenia
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
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Gastrointestinal disorders
Colitis
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28.1%
9/32 • Number of events 9 • From time of consent until 30 after last treatment. Up to 1 year.
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Skin and subcutaneous tissue disorders
Pruritius
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9.4%
3/32 • Number of events 3 • From time of consent until 30 after last treatment. Up to 1 year.
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Immune system disorders
Hypophysitis
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6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
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Skin and subcutaneous tissue disorders
Rash
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9.4%
3/32 • Number of events 3 • From time of consent until 30 after last treatment. Up to 1 year.
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Other adverse events
| Measure |
Treatment-CP-675,206
n=32 participants at risk
See intervention descriptions
CP-675,206: Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.
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|---|---|
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Blood and lymphatic system disorders
thrombocytopenia
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6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
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Respiratory, thoracic and mediastinal disorders
dyspena
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12.5%
4/32 • Number of events 4 • From time of consent until 30 after last treatment. Up to 1 year.
|
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Cardiac disorders
hypotension
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
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General disorders
tumor pain
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
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Cardiac disorders
tachycardia
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Skin and subcutaneous tissue disorders
rash
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18.8%
6/32 • Number of events 6 • From time of consent until 30 after last treatment. Up to 1 year.
|
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General disorders
ertherma biopsy site
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
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Infections and infestations
bronchitis
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Infections and infestations
fever
|
9.4%
3/32 • Number of events 3 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Skin and subcutaneous tissue disorders
pruritus
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6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
nausea
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9.4%
3/32 • Number of events 3 • From time of consent until 30 after last treatment. Up to 1 year.
|
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General disorders
insomnia
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
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General disorders
itchness
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Gastrointestinal disorders
diarrhea
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12.5%
4/32 • Number of events 4 • From time of consent until 30 after last treatment. Up to 1 year.
|
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Eye disorders
loss of right eye vision
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
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General disorders
lower back pain
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6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Renal and urinary disorders
nocturia
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3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
sleepiness
|
6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
night sweats
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
neck pain
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
anemia
|
6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
fatigue
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
asthenia
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
headaches
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
right hip pain
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Gastrointestinal disorders
colitis
|
6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
abdominal pain
|
6.2%
2/32 • Number of events 2 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
weight loss
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Renal and urinary disorders
acute renal failure
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
dizziness
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
depression
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
anxiety
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Infections and infestations
cold
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Eye disorders
diplopia
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Blood and lymphatic system disorders
hypophysitis
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
leg twitiching
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Gastrointestinal disorders
perforated colon
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
left side pain
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Nervous system disorders
brain metastasis
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
left nares maxilla swelling
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
left nares maxilla bleeding
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
shortness of breath
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
bleeding lesion
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
confusion
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
oozing from bulky right axillary mass
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
Skin and subcutaneous tissue disorders
groves disease
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
|
General disorders
edema left low extremity
|
3.1%
1/32 • Number of events 1 • From time of consent until 30 after last treatment. Up to 1 year.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place