Trial Outcomes & Findings for Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma (NCT NCT03436732)

Last Updated: 2019-11-22

Results Overview

Here are the grade ≥3 adverse events at each dose level assessed by the Common Terminology Criteria in Adverse Events CTCAE v5.0. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is Severe or medically significant but not immediately life-threatening;hospitalization or prolongation of hospitalization indicated; disabling;limiting self care ADL (i.e., bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 is life-threatening consequences;urgent intervention indicated. Grade 5 is death related to adverse event.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

5 participants

Primary outcome timeframe

Day 85

Results posted on

2019-11-22

Participant Flow

1/5 participants enrolled was a screen failure following enrollment.

Participant milestones

Participant milestones
Measure	140 mcg/kg LMB-100 + SEL-110 Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	100 mcg/kg LMB-100 + SEL-110 Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles
Overall Study STARTED	4	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	140 mcg/kg LMB-100 + SEL-110 Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	100 mcg/kg LMB-100 + SEL-110 Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles
Overall Study Not treated-enrolled in different study	1	0
Overall Study Off study after cycle 1	1	0
Overall Study Adverse Event	2	0
Overall Study Death	0	1

Baseline Characteristics

Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Day 85

Outcome measures

Outcome measures
Measure	140 mcg/kg n=4 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	100 mcg/kg n=1 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles
Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg Grade 4 pericardial effusion	1 Participants	0 Participants
Number of Participants With Grade ≥3 Adverse Events Related to Study Drug at Dose Level 140 mcg/kg and 100 mcg/kg Grade 5 pneumonitis	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Day 21

Population: MTD was not found because the study was closed due to a fatal occurrence of pneumonitis that was attributed to one of the study drugs.

MTD is defined as the highest tested dose of LMB-100 and SEL-110 at which no more than 1 of 6 subjects experience a dose limiting toxicity. A dose limiting toxicity is defined as any of the following: Grade 4 neutropenia for a minimum duration of 7 days. Grade 4 thrombocytopenia (≤25.0 x 10(9) cells/L), Grade 3 thrombocytopenia associated with bleeding episodes, and Grade 4 anemia. Grade ≥3 non-hematological toxicity with the exception of Alopecia (any grade), Grade 3 nausea and vomiting lasting \> 48 hours despite appropriate treatment, Grade 3 diarrhea lasting for ≤ 2 days with no fever or dehydration, and laboratory values of ≥ grade 3 that are judged not clinically significant by the investigator. Any other drug related toxicity considered significant enough to be qualified as a DLT in the opinion of the principal investigator. Inability to start cycle 2 within 3 weeks after completing cycle 1 due to drug-related adverse events.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days

Response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesion, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	140 mcg/kg n=4 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	100 mcg/kg n=1 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles
Number of Participants With Partial Response or Complete Response (PR + CR) Complete Response	0 Participants	0 Participants
Number of Participants With Partial Response or Complete Response (PR + CR) Partial Response	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 85

Population: This outcome measure was not done because the study was closed due to a fatal occurrence of pneumonitis that was attributed to one of the study drugs.

Blood is measured for a detectable level of LMB-100 in the blood. LMB-100 is either detectable in the blood or not. A detectable level of LMB-100 in the blood is considered a desirable outcome for the participant. Hence, the reverse is not a considered a desirable outcome for the participant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	140 mcg/kg n=4 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	100 mcg/kg n=1 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles
Number of Participants With Serious and Non-Serious Adverse Events	3 Participants	1 Participants

Adverse Events

140 mcg/kg LMB-100 + SEL-110

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

100 mcg/kg LMB-100 + SEL-110

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Raffit Hassan

National Cancer Institute

Phone: 240-760-6322

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	140 mcg/kg LMB-100 + SEL-110 n=4 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	100 mcg/kg LMB-100 + SEL-110 n=1 Participants Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	65.75 years STANDARD_DEVIATION 2.278 • n=5 Participants	58 years STANDARD_DEVIATION 0 • n=7 Participants	63 years STANDARD_DEVIATION 5.86 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants

Measure	140 mcg/kg LMB-100 + SEL-110 n=4 participants at risk Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles	100 mcg/kg LMB-100 + SEL-110 n=1 participants at risk Dose escalation - patients with mesothelioma treated with LMB-100+SEL-110 at escalating doses LMB-100: administered on days 1, 3 and 5 of each 21 day cycle for up to 4 cycles SEL-110: administered on day 1 of each cycle for up to 4 cycles
Infections and infestations Lung infection	0.00% 0/4 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/4 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Cardiac disorders Atrial fibrillation	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Vascular disorders Capillary leak syndrome	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
General disorders Disease progression	50.0% 2/4 • Number of events 2 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Respiratory, thoracic and mediastinal disorders Hypoxia	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Injury, poisoning and procedural complications Infusion related reaction	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Musculoskeletal and connective tissue disorders Non-cardiac chest pain	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Cardiac disorders Pericardial effusion	25.0% 1/4 • Number of events 3 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Cardiac disorders Pericardial tamponade	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Cardiac disorders Pericarditis	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Respiratory, thoracic and mediastinal disorders Pleural effusion	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.	0.00% 0/1 • Date treatment consent signed to date off study, approximately one month and 25 days for the 100 mcg/kg Arm/Group, and 9 months and 28 days for the 140 mcg/kg Arm/Group.