Trial Outcomes & Findings for Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma (NCT NCT01112293)
NCT ID: NCT01112293
Last Updated: 2020-04-10
Results Overview
The fraction of subjects surviving 3 months without disease progression.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
14 participants
Primary outcome timeframe
3 months
Results posted on
2020-04-10
Participant Flow
Participant milestones
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Overall Study
STARTED
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14
|
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Overall Study
COMPLETED
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14
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma
Baseline characteristics by cohort
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=14 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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3 Participants
n=5 Participants
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Age, Categorical
>=65 years
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11 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
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2 Participants
n=5 Participants
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Sex: Female, Male
Male
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12 Participants
n=5 Participants
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Region of Enrollment
United States
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14 participants
n=5 Participants
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PRIMARY outcome
Timeframe: 3 monthsPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
The fraction of subjects surviving 3 months without disease progression.
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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3-month Progression Free Survival Rate
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3 Participants
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SECONDARY outcome
Timeframe: 18 monthsPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
The toxicity and safety of systemic infusion of anti-TGF antibody at three-week dosing intervals. Number subjects with Grade 2 and Grade 3/4 treatment related toxicities.
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Toxicity and Safety of Systemic Infusion of Anti-TGF Antibody
Grade 2 Treatment Related Toxicities
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4 participants
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Toxicity and Safety of Systemic Infusion of Anti-TGF Antibody
Grade 3/4 Treatment Related Toxicities
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3 participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 18 monthsPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
Assessment of time to disease progression and overall survival
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Time to Progression and Overall Survival
Overall Survival
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12 Months
Interval 7.17 to 14.43
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Time to Progression and Overall Survival
Time to Progression
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1.4 Months
Interval 1.2 to
Data was reported as a one sided Confidence Interval, so there is no upper limit interval reported
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OTHER_PRE_SPECIFIED outcome
Timeframe: 18 monthsPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
Response and progression will be evaluated in this study using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in RECIST. The response assessment is based on the presence, absence, or unequivocal progression of the lesions.
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Response Rate Using Modified RECIST Criteria for Mesothelioma
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0 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 18 monthsPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
Evaluation of changes after treatment therapy to a number of potential blood biomarkers of TGF-β effect (serum osteopontin, serum hyaluronan, serum MMP-1, serum MMP-7, serum IL-6, plasma CCL18, plasma VEGF, and plasma PAI-1). Animal models predict acute changes in TGF-β levels in blood associated with changes in serum biomarkers.
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in serum osteopontin after treatment
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0 Participants
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in serum hyaluronan after treatment
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0 Participants
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in serum MMP-1 after treatment
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0 Participants
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in serum MMP-7 after treatment
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0 Participants
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in serum IL-6 V after treatment
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0 Participants
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in plasma CCL18 v after treatment
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0 Participants
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in plasma VEGF after treatment
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0 Participants
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Number of Participants With a Change of Serum Biomarkers After Therapy
Change in plasma PAI-1 after treatment
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0 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 18 monthsPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
Comparing antibody bands in pre-treatment versus post-treatment serum
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Number of Participants With Systemic Humoral Anti-tumor Immune Response After Repeated Anti-TGFβ Antibody Instillation
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6 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 18 monthsPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
The number of participants with significant change in percentage of circulating CD4+ T regulatory cells, marked by expression of FOXP3 after treatment. TGFβ has been implicated in the formation of T regulatory cells, and the blockade of TGFβ in animal models can inhibit the formation of T regulatory cells.
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Assessment of Systemic TGFβ After Repeated Anti-TGFβ Antibody Installation
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0 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: 3 weeksPopulation: Outcome analysis presented in manuscript of results of trial based on 13 participants.
Number of participants who demonstrated upregulation of NK cell receptors 3 weeks after treatment. There are data that show anti-TGFβ antibodies can upregulate NK cell receptors in patients with chronic viral infections. TGFβ blockade was measured in samples of serum tests and from pleural fluid or biopsy if available.
Outcome measures
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=13 Participants
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Biologic Response Measurements of TGFβ Blockade
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0 Participants
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Adverse Events
Investigational Drug infusion-for Safety and Effectiveness
Serious events: 6 serious events
Other events: 12 other events
Deaths: 12 deaths
Serious adverse events
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=14 participants at risk
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment.
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Gastrointestinal disorders
Nausea
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7.1%
1/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Metabolism and nutrition disorders
Hyponatremia
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7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Respiratory, thoracic and mediastinal disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Cardiac disorders
Fatigue
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7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Blood and lymphatic system disorders
Thrombosis
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7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Respiratory, thoracic and mediastinal disorders
Disease Progression
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14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Blood and lymphatic system disorders
Fever
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7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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General disorders
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7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Gastrointestinal disorders
Ileus
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7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Other adverse events
| Measure |
Investigational Drug infusion-for Safety and Effectiveness
n=14 participants at risk
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment.
GC1008: GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.
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|---|---|
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Metabolism and nutrition disorders
Anorexia
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42.9%
6/14 • Number of events 6 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Cardiac disorders
Fatigue
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64.3%
9/14 • Number of events 11 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Gastrointestinal disorders
Dysphagia
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14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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General disorders
Non-Cardiac Chest Pain
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21.4%
3/14 • Number of events 3 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Respiratory, thoracic and mediastinal disorders
Hoarseness
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7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Respiratory, thoracic and mediastinal disorders
Epistaxis
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21.4%
3/14 • Number of events 3 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Respiratory, thoracic and mediastinal disorders
Cough
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28.6%
4/14 • Number of events 5 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Gastrointestinal disorders
Constipation
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14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Gastrointestinal disorders
Dyspepsia
|
14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Injury, poisoning and procedural complications
Back Pain
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14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Infections and infestations
Lung Infection
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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|
Gastrointestinal disorders
Vomiting
|
14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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|
Gastrointestinal disorders
Nausea
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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|
Metabolism and nutrition disorders
Hyponatremia
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
Blood and lymphatic system disorders
Anemia
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
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Infections and infestations
Mucosal Infection
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
General disorders
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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|
Skin and subcutaneous tissue disorders
Dry Skin
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
General disorders
Pain
|
14.3%
2/14 • Number of events 2 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
General disorders
Edema Limbs
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
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Musculoskeletal and connective tissue disorders
Chest Wall Pain
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
Cardiac disorders
Pericardial effusion
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
Gastrointestinal disorders
Abdominal distension
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
|
|
Cardiac disorders
Chest Pain
|
7.1%
1/14 • Number of events 1 • Adverse event data was collected from time of first administration of study product until 30 days of the last administration of study product, approximately 1 year and 5 months.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place