Trial Outcomes & Findings for Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine for Mesothelin Expressing Lung Adenocarcinoma (NCT NCT02839681)

Last Updated: 2019-05-21

Results Overview

The highest dose tested at which no more than 1 dose limiting toxicity occurs. A dose limiting toxicity is defined as any treatment emergent adverse event (TEAE) (i.e., absolute neutrophil count \<500/mm\^3 for ≥7 days) occurring during Cycle 1 and regarded to be at least possibly related to anetumab ravtansine.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

21 days after initiation of study therapy

Results posted on

2019-05-21

Participant Flow

Per protocol: Phase 2 Cohort was not performed because we did not accrue at least 6 subjects in the Safety run-in cohort. The first 6 evaluable subjects enrolled in whom the higher of 2 de-escalating doses of anetumab ravtansine will be evaluated in order to determine the recommended Phase 2 dose.

Participant milestones

Participant milestones
Measure	1/Safety Run-in Arm Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Overall Study STARTED	2
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	1/Safety Run-in Arm Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Overall Study Death	2

Baseline Characteristics

Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine for Mesothelin Expressing Lung Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1/Safety Run-in Arm n=2 Participants Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	58.0 years STANDARD_DEVIATION 2.8 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 21 days after initiation of study therapy

Population: This outcome measure was not done because the study was terminated due to slow, insufficient accrual.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 6 weeks

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). A complete response is disappearance of all target lesions. A partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	1/Safety Run-in Arm n=2 Participants Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Proportion of Subjects Who Experienced a Partial or Complete Response Partial Response	0 proportion of participants
Proportion of Subjects Who Experienced a Partial or Complete Response Complete Response	0 proportion of participants

SECONDARY outcome

Timeframe: At Disease Progression, approximately 6 weeks.

Length of time from start of treatment to time of progression or death, whichever occurs first. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, 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. (Note: the appearance of one or more new lesions is also considered progressions).

Outcome measures

Outcome measures
Measure	1/Safety Run-in Arm n=2 Participants Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Progression Free Survival	5.5 Weeks Interval 5.3 to 5.7

SECONDARY outcome

Timeframe: At Disease Progression, approximately 6 weeks from start of treatment

Population: No participant met the criteria for a complete response or partial response.

Duration of Response is from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR). Length of time criteria are met for partial response or complete response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, 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. (Note: the appearance of one or more new lesions is also considered progressions). A complete response is disappearance of all target lesions. A partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Death, an average of 7.5 weeks after start of first cycle for both patients.

Length of time from start of treatment to death from any cause.

Outcome measures

Outcome measures
Measure	1/Safety Run-in Arm n=2 Participants Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Overall Survival	7.6 Weeks Interval 5.7 to 9.6

SECONDARY outcome

Timeframe: Participants on the Safety run-in phase was assessed for approximately two months and 5 days.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). 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	1/Safety Run-in Arm n=2 Participants Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	2 Participants

Adverse Events

1/Safety Run-in Arm

Serious events: 1 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	1/Safety Run-in Arm n=2 participants at risk Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Respiratory, thoracic and mediastinal disorders Respiratory failure	50.0% 1/2 • Number of events 1 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.

Other adverse events

Other adverse events
Measure	1/Safety Run-in Arm n=2 participants at risk Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study Anetumab Ravtansine: Administered intravenously (IV) every 3 weeks Blood test: Research blood test for eligibility
Gastrointestinal disorders Abdominal pain	50.0% 1/2 • Number of events 1 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Investigations Activated partial thromboplastin time prolonged	50.0% 1/2 • Number of events 1 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Investigations Alkaline phosphatase increased	100.0% 2/2 • Number of events 3 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
General disorders Fatigue	50.0% 1/2 • Number of events 1 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Metabolism and nutrition disorders Hypercalcemia	100.0% 2/2 • Number of events 3 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 2/2 • Number of events 3 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Blood and lymphatic system disorders Anemia	100.0% 2/2 • Number of events 2 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Investigations Lymphocyte count decreased	100.0% 2/2 • Number of events 2 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Investigations Platelet count decreased	100.0% 1/1 • Number of events 1 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.
Skin and subcutaneous tissue disorders Rash maculo-papular	100.0% 1/1 • Number of events 1 • Participants on the Safety run-in phase was assessed for approximately two months and 5 days.

Additional Information

Dr. Raffit Hassan

National Cancer Institute

Phone: 240-760-6232

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place