Trial Outcomes & Findings for Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM) (NCT NCT02610140)

Last Updated: 2020-11-04

Results Overview

Progression-free survival (PFS), defined as time from randomization until disease progression according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) for Malignant pleural mesothelioma (MPM) per blinded central radiology review, or death. Only descriptive analysis of OS was repeated in the follow-up period.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

248 participants

Primary outcome timeframe

From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)

Results posted on

2020-11-04

Participant Flow

Overall, 315 patients were screened; of these, 67 patients were screening failures.

Participant milestones

Participant milestones
Measure	Anetumab Ravtansine (Experimental) Experimental	Vinorelbine (Active Comparator) Active comparator
Randomization and Treatment Period STARTED	166	82
Randomization and Treatment Period Participants Received Treatment	163	72
Randomization and Treatment Period COMPLETED	0	0
Randomization and Treatment Period NOT COMPLETED	166	82
Safety Follow-up STARTED	102	45
Safety Follow-up COMPLETED	57	21
Safety Follow-up NOT COMPLETED	45	24
Active Follow-up STARTED	48	26
Active Follow-up COMPLETED	0	0
Active Follow-up NOT COMPLETED	48	26
Long-term Follow-up STARTED	123	66
Long-term Follow-up COMPLETED	0	0
Long-term Follow-up NOT COMPLETED	123	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Anetumab Ravtansine (Experimental) Experimental	Vinorelbine (Active Comparator) Active comparator
Randomization and Treatment Period Radiological progression	23	15
Randomization and Treatment Period Progressive disease - radiological	54	23
Randomization and Treatment Period Protocol Violation	1	0
Randomization and Treatment Period Physician Decision	0	1
Randomization and Treatment Period Lack of Efficacy	1	0
Randomization and Treatment Period Death	7	1
Randomization and Treatment Period Withdrawal by Subject	12	12
Randomization and Treatment Period Adverse Event	44	13
Randomization and Treatment Period Progressive disease - clinical	12	5
Randomization and Treatment Period Ongoing but not completed	9	2
Randomization and Treatment Period Not treated	3	10
Safety Follow-up Other	0	2
Safety Follow-up Lost to Follow-up	1	0
Safety Follow-up No follow-up	5	3
Safety Follow-up Death	12	2
Safety Follow-up Deterioration of general conditions	15	5
Safety Follow-up Withdrawal by Subject	12	12
Active Follow-up Progressive disease - radiological	30	22
Active Follow-up Death	8	1
Active Follow-up Withdrawal by Subject	4	0
Active Follow-up Progressive disease - clinical	1	2
Active Follow-up Deterioration of general conditions	1	0
Active Follow-up Ongoing but not completed	4	1
Long-term Follow-up Death	86	44
Long-term Follow-up Withdrawal by Subject	6	3
Long-term Follow-up Lost to Follow-up	1	2
Long-term Follow-up Ongoing but not completed	30	17

Baseline Characteristics

Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anetumab Ravtansine (Experimental) n=166 Participants Experimental	Vinorelbine (Active Comparator) n=82 Participants Active comparator	Total n=248 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	66 Participants n=5 Participants	37 Participants n=7 Participants	103 Participants n=5 Participants
Age, Categorical >=65 years	100 Participants n=5 Participants	45 Participants n=7 Participants	145 Participants n=5 Participants
Age, Continuous	66.1 Years STANDARD_DEVIATION 8.1 • n=5 Participants	65.6 Years STANDARD_DEVIATION 8.8 • n=7 Participants	65.9 Years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	20 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	122 Participants n=5 Participants	62 Participants n=7 Participants	184 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	2 Participants n=5 Participants	1 Participants n=7 Participants	3 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	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	157 Participants n=5 Participants	75 Participants n=7 Participants	232 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	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)

Population: The primary efficacy analysis (PFS) was performed in the ITT (Intent-to-treat) analysis set.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Progression-free Survival (PFS), [95% CI]	4.3 months Interval 4.1 to 5.5	4.5 months Interval 4.1 to 5.8

SECONDARY outcome

Timeframe: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause; one-sided log-rank test stratified by time to progression (TTP) on first line treatment.

Population: The secondary efficacy analysis (OS) was performed in the ITT (Intent-to-treat) analysis set.

Overall survival (OS) was defined as time from randomization until death from any cause.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Overall Survival (OS), [95% CI]	9.5 months Interval 8.3 to 12.3	11.6 months Interval 8.6 to 13.1

SECONDARY outcome

Timeframe: up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause.

Population: The secondary efficacy analysis (ORR) was performed in the ITT (Intent-to-treat) analysis set.

A patient is a responder if the patient has a confirmed best tumor response on-study of CR (Complete response) or PR (Partial response), as determined by the central radiological reviewer per mRECIST criteria. ORR in each treatment arm was defined as the number of responders divided by the number of randomized patients. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Objective Response Rate (ORR)	8.4 percentage of participants Interval 4.7 to 13.7	6.1 percentage of participants Interval 2.0 to 13.7

SECONDARY outcome

Timeframe: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

Population: The secondary efficacy analysis (DCR) was performed in the ITT (Intent-to-treat) analysis set.

A patient has disease control if the patient has a best tumor response on-study of CR, PR, or SD (Stable disease). DCR was defined as a percentage of patients achieving CR, PR, or SD per mRECIST criteria, as determined by the central radiological reviewer. DCR was calculated in each treatment arm as the number of patients with disease control (a best tumor response on-study of CR, PR, or SD) divided by the number of randomized patients.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Disease Control Rate (DCR)	73.5 percentage of participants Interval 66.1 to 80.0	68.3 percentage of participants Interval 57.1 to 78.1

SECONDARY outcome

Timeframe: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

Population: The secondary efficacy analysis (DOR) was performed in the ITT (Intent-to-treat) analysis set.

DOR was defined in responders as the time from central documentation of tumor response date of first response in the confirmation sequence) to the earlier of disease progression as determined by the central radiological reviewer, or death without centrally documented progression. A responder was a patient who had a confirmed best tumor response on-study of CR or PR, as determined by the central radiological reviewer per mRECIST criteria.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Duration of Response (DOR)	7.4 months Interval 6.0 to NA = value cannot be estimated due to censored data	6.7 months Interval 3.0 to 10.3

SECONDARY outcome

Timeframe: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

Population: The secondary efficacy analysis (DRR) was performed in the ITT (Intent-to-treat) analysis set.

A durable responder was a responder (i.e. confirmed best tumor response on study of CR or PR) with duration of response of 180 days or more.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Durable Response Rate (DRR)	7.2 percentage of participants Interval 3.8 to 12.3	4.9 percentage of participants Interval 1.3 to 12.0

SECONDARY outcome

Timeframe: up to approx. 30 months (data cut-off: 31-May-2017)

Population: The secondary efficacy analysis was performed in the ITT (Intent-to-treat) analysis set.

Improvement rate of symptoms characteristic of mesothelioma was defined as the number of patients with confirmed improvement of symptoms characteristic of mesothelioma (based on the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma, MDASI-MPM), divided by the number of patients evaluable for improvement of symptoms characteristic of mesothelioma.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Percentage of Participants With Confirmed Improvement of Symptoms Characteristic of Mesothelioma	22.5 percentage of participants Interval 15.1 to 31.4	17.9 percentage of participants Interval 8.9 to 30.4

SECONDARY outcome

Timeframe: up to approx. 30 months (data cut-off: 31-May-2017)

Population: The secondary efficacy analysis was performed in the ITT (Intent-to-treat) analysis set.

Time to worsening of symptoms characteristic of mesothelioma (TTWS) was defined in patients evaluable for assessing worsening of symptoms, as the time from randomization until the first worsening of symptoms characteristic of mesothelioma. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of symptoms were censored at the date of their last MDASI-MPM assessment with a non-missing (Composite Symptom Score) CSS.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Time to Worsening of Symptoms Characteristic of Mesothelioma	NA days value cannot be estimated due to censored data	NA days value cannot be estimated due to censored data

SECONDARY outcome

Timeframe: up to approx. 30 months (data cut-off: 31-May-2017)

Population: The secondary efficacy analysis was performed in the ITT (Intent-to-treat) analysis set.

Time to worsening of pain (TTWP) was defined in patients evaluable for assessing worsening of pain, as time from randomization until the first worsening of pain. Patients who died, were lost to follow-up, or ended (MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma) MDASI-MPM assessments without confirmed worsening of pain were censored at the date of their last MDASI-MPM assessment with a non-missing pain score.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Time to Worsening of Pain	210 days Interval 127.0 to value cannot be estimated due to censored data	NA days Interval 85.0 to value cannot be estimated due to censored data

SECONDARY outcome

Timeframe: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

Population: The secondary efficacy analysis was performed in the ITT (Intent-to-treat) analysis set.

Improvement rate of pain was defined as the number of patients with confirmed improvement of pain (based on the "pain at its worst" item of MDASI-MPM), divided by the number of patients evaluable for improvement of pain.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Percentage of Participants With Confirmed Improvement of Pain	40.4 percentage of participants Interval 30.9 to 50.5	32.7 percentage of participants Interval 19.9 to 47.5

SECONDARY outcome

Timeframe: Up to approx. 55 months (data cut-off: 02-Jul-2019) - Time from randomization until 30 days after last treatment (general AEs), or further until death from any cause (selected AEs).

Population: The secondary efficacy analysis (TEAEs) was performed in the safety analysis set (SAF).

TEAEs were defined as all AEs starting or worsening within the treatment period.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=163 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=72 Participants Active comparator: 30 mg/m\^2 once weekly
Percentage of Participant With Treatment-emergent Adverse Events (TEAEs) Any TEAE	99.4 Percentage of participants	98.6 Percentage of participants
Percentage of Participant With Treatment-emergent Adverse Events (TEAEs) Any study drug-related TEAE	88.3 Percentage of participants	90.3 Percentage of participants
Percentage of Participant With Treatment-emergent Adverse Events (TEAEs) Treatment-emergent serious adverse events (TESAEs)	34.4 Percentage of participants	34.7 Percentage of participants

SECONDARY outcome

Timeframe: Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.

Population: The secondary efficacy analysis (TEAEs) was performed in the safety analysis set (SAF).

TEAE(s) associated with a fatal outcome (CTCAE Grade 5) at the time of the data cut-off 06-Apr-2018.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=163 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=72 Participants Active comparator: 30 mg/m\^2 once weekly
Number of Deaths	10 Number of Deaths	1 Number of Deaths

SECONDARY outcome

Timeframe: Up to approx. 55 month (data cut-off: 02-JUL-2019) - Time from randomization until death from any cause

Population: The secondary efficacy analysis (OS) was performed in the ITT (Intent-to-treat) analysis set.

Overall survival (OS) was defined as time from randomization until death from any cause; Only descriptive analyses of OS were repeated in with the data as of the 02 JUL 2019.

Outcome measures

Outcome measures
Measure	Anetumab Ravtansine n=166 Participants Test drug: 6.5 mg/kg every 3 weeks; Intravenous (IV) infusion over 1 hour	Vinorelbine n=82 Participants Active comparator: 30 mg/m\^2 once weekly
Overall Survival (OS) - Addendum	9.5 months Interval 8.3 to 12.3	11.6 months Interval 8.6 to 13.1

Adverse Events

Anetumab Ravtansine (BAY94-9343)

Serious events: 56 serious events

Other events: 161 other events

Deaths: 126 deaths

Vinorelbine

Serious events: 25 serious events

Other events: 68 other events

Deaths: 55 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

Bayer AG

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The agreed point of publication is 12-18 months after database lock at the earliest. Bayer will have 30-45 days to review publications, and may request an additional publication delay of up to 60 days to allow for filing a Patent Application (if applicable). No publication of single center data should be done prior of publication if multi-center data.
Publication restrictions are in place

Restriction type: OTHER