Trial Outcomes & Findings for Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated (NCT NCT01332721)

Last Updated: 2018-12-05

Results Overview

Three patients will be initially enrolled and treated at each dose level. If none of these 3 patients experiences a dose-limiting toxicity (DLT) during the 28-day evaluation period, dose escalation will proceed following review of safety data with appropriate site staff including the principal investigators at all sites. If 1 of 3 patients experiences DLT, the cohort will be expanded to 6 patients. The maximum tolerated dose (MTD) will have been exceeded if ≥ 33% of patients experience DLT in a given cohort. DLT will have occurred when a patient has 1 or more toxicity listed in the table below that is at least possibly related to the combination of bevacizumab and TRC105 during the first 28 days (cycle 1).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

38 participants

Primary outcome timeframe

1.5 years

Results posted on

2018-12-05

Participant Flow

Participant milestones

Participant milestones
Measure	TRC105 and Bevacizumab Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.
Overall Study STARTED	38
Overall Study COMPLETED	38
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TRC105 and Bevacizumab n=38 Participants Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.
Age, Continuous	63 Years n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Prior VEGF inhibitor treatment Prior VEGF inhibitor treatment	30 participants n=5 Participants
Prior VEGF inhibitor treatment No prior VEGF inhibitor treatment	8 participants n=5 Participants

PRIMARY outcome

Timeframe: 1.5 years

Outcome measures

Outcome measures
Measure	TRC105 and Bevacizumab n=38 Participants Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.
Determine Maximum Tolerated Dose of TRC105 in Combination With Bevacizumab	10 mg/kg

SECONDARY outcome

Timeframe: 1.5 years

Plasma TRC105 concentrations will be measured at specified timepoints.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1.5 years

HAMA and HACA titers will be measured at specified time-points.

Outcome measures

Outcome measures
Measure	TRC105 and Bevacizumab n=26 Participants Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.
Immune Response to TRC105 HAMA POSITIVE	3 participants
Immune Response to TRC105 HAMA NEGATIVE	23 participants
Immune Response to TRC105 HACA POSITIVE	4 participants
Immune Response to TRC105 HACA NEGATIVE	22 participants

SECONDARY outcome

Timeframe: 1.5 years

The best response according to RECIST 1.1 for each patient with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type

Outcome measures

Outcome measures
Measure	TRC105 and Bevacizumab n=31 Participants Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.
Objective Response According to RECIST 1.1 RECIST 1.1 defined response	2 participants
Objective Response According to RECIST 1.1 Tumor burden decreases	14 participants

Adverse Events

TRC105 and Bevacizumab

Serious events: 9 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TRC105 and Bevacizumab n=38 participants at risk Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.
Gastrointestinal disorders Ileus	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Infections and infestations Cellulitis of Left Foot	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Respiratory, thoracic and mediastinal disorders Recurrent pneumothorax	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Nervous system disorders Headache	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
General disorders disease progression	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Infections and infestations Pneumonia	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Infections and infestations MRSA Sepsis	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Infections and infestations Sepsis	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Infections and infestations Brain Absces	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Gastrointestinal disorders Small Bowel Obstruction	2.6% 1/38 • Number of events 1 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.

Other adverse events

Other adverse events
Measure	TRC105 and Bevacizumab n=38 participants at risk Escalating doses of TRC105 were studied in combination with standard dose bevacizumab. In accordance with the original protocol, patients in cohorts 1 and 2 received TRC105 on day 1, day 8, and day 15 and bevacizumab on day 1 of each 3 week cycle. Cohort 3 and 4 patients received TRC105 on days 8, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle), and cohort 4a and 5 patients received TRC105 on days 8, 11, 15, and 22 and bevacizumab on days 1 and 15 of cycle 1 (4 week cycle). Beyond cycle 1, patients in cohorts 3, 4, 4a, and 5 received TRC105 on days 1, 8, 15 and 22 and bevacizumab on days 1 and 15 of each 4 week cycle.
Blood and lymphatic system disorders Anaemia	28.9% 11/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Endocrine disorders Hypothyroidism	5.3% 2/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Eye disorders Periorbital oedema	5.3% 2/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Gastrointestinal disorders Gingival pain	10.5% 4/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Gastrointestinal disorders Nausea	7.9% 3/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Gastrointestinal disorders Oral pain	7.9% 3/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Gastrointestinal disorders Vomiting	5.3% 2/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
General disorders Face oedema	10.5% 4/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
General disorders Fatigue	26.3% 10/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Injury, poisoning and procedural complications Infusion related reaction	28.9% 11/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Metabolism and nutrition disorders Decreased appetite	10.5% 4/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Nervous system disorders Headache	81.6% 31/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Nervous system disorders Migraine	7.9% 3/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Nervous system disorders Sinus headache	5.3% 2/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 2/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.9% 3/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Skin and subcutaneous tissue disorders Rash	7.9% 3/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Vascular disorders Epistaxis	65.8% 25/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Vascular disorders Flushing	21.1% 8/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Vascular disorders Gingival bleeding	31.6% 12/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.
Vascular disorders Telangiectasia	50.0% 19/38 • The adverse event reporting period for this trial started when a given patient had the first dose of bevacizumab and/or TRC105 study drug and ended 28 days after the last dose of bevacizumab and/or TRC105 study drug was administered whichever was later. In addition, any known untoward event that occurred beyond the adverse event reporting period that the Investigator assessed as possibly related to TRC105 and/or bevacizumab was reported as an adverse event.

Additional Information

Dr Charles Theuer

TRACON Pharmaceuticals

Phone: 8585500780

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60