An Efficacy Study of MORAb-009 (Amatuximab) in Subjects With Pleural Mesothelioma

Study Overview
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Brief Summary
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This research is being done to find out if pemetrexed and cisplatin work better when given together with an experimental drug called MORAb-009 in patients with malignant pleural mesothelioma.

Official Title
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An Open-Label Clinical Trial of MORAb-009 in Combination With Pemetrexed and Cisplatin in Subjects With Mesothelioma

Conditions
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Malignant Pleural Mesothelioma

Intervention / Treatment
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* Drug: MORAb-009 (Amatuximab)
* Drug: Pemetrexed
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Primary Inclusion Criteria: Confirmed diagnosis of malignant pleural mesothelioma (MPM) with the following characteristics: unresectable disease (or otherwise not a candidate for curative surgery); epithelial type or biphasic (mixed) type with low sarcomatous content. Measurable disease at Screening by computed tomography (CT)(or magnetic resonance imaging [MRI]). KPS of greater than or equal to 70% at Screening. Life expectancy of at least 3 months Primary Exclusion Criteria: Sarcomatous type of mesothelioma Prior systemic therapy or radiotherapy for MPM; local radiotherapy for symptom control (ie, non-curative intent) is permitted. Confirmed presence of CNS tumor involvement. Evidence of other active malignancy requiring treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label<br>Pemetrexed, Cisplatin and MORAb-009 (Amatuximab) | Drug: MORAb-009 (Amatuximab)<br>* MORAb-009 (Amatuximab) by IV on Days 1 and 8 every 21 days for 6 cycles.<br>Drug: Pemetrexed<br>* Pemetrexed 500 mg/m2 on Day 1 of each 21-day cycle for 6 cycles<br>Drug: Cisplatin<br>* Cisplatin 75 mg/m2 on Day 1 of each 21-day cycle for 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progression Free Survival (PFS) Responders and Non-responders at Month 6 | Number of participants with PFS responders and non-responders at Month 6 was reported. PFS was defined as the time from the date of the first dose of amatuximab to the date of disease progression or death due to any cause, as determined by independent radiologist based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) utilizing the total tumor measurement (performed by computerized tomography (CT)/magnetic resonance imaging (MRI)) which includes the pleural unidimensional measure plus the total of the target lesion(s) measurement. A response, in terms of PFS, was defined to be at least a 6-month stabilization of disease. Progressive disease (PD) as measured by Modified RECIST was defined as an increase of at least 20 percent (%) in the total tumor measurement over the nadir measurement, or the appearance of one or more new lesions. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR, defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) as determined by independent radiologist based on the modified RECIST utilizing the total tumor measurement (performed by CT/ MRI) which includes the pleural unidimensional measure plus the total of the target lesion(s) measurement. Tumor assessments performed up to the initiation of further anticancer therapy were considered. CR was defined as the disappearance of all target lesions with no evidence of tumor elsewhere, and PR was defined as at least a 30% reduction in the total tumor measurement. A confirmed response required a repeat observation on two occasions 4 weeks apart. ORR = CR + PR. | From the date of first dose until evidence of CR or PR, up to approximately 5 years | 
| Duration of Response (DR) | DR was derived for those participants who achieved a PFS Response and had an objective evidence of CR or PR. DR was defined as the time (in months) from first documentation of objective response (CR or PR) to the first documentation of disease progression or death [as determined by independent radiologist based on the modified RECIST utilizing the total tumor measurement (performed by CT/ MRI) which includes the pleural unidimensional measure plus the total of the target lesion(s) measurement]. Tumor assessments performed up to the initiation of further anticancer therapy were considered. CR was defined as the disappearance of all target lesions with no evidence of tumor elsewhere, and PR was defined as at least a 30% reduction in the total tumor measurement. PD as measured by Modified RECIST was defined as an increase of at least 20% in the total tumor measurement over the nadir measurement, or the appearance of one or more new lesions. | From the first documentation of objective response (CR or PR) to the first documentation of disease progression, up to approximately 5 years | 
| Time to Tumor Response (TTR) | TTR was derived for those participants with objective evidence of CR or PR. TTR was defined as the time from the date of the first dose of amatuximab to first documentation of objective tumor response. CR was defined as the disappearance of all target lesions with no evidence of tumor elsewhere, and PR was defined as at least a 30% reduction in the total tumor measurement. | From the date of the first dose to first documentation of objective response, up to approximately 5 years | 
| Overall Survival (OS) | OS was defined as the time from the date of the first dose of amatuximab to the date of death. | From the date of first dose to the date of death, up to approximately 5 years | 
| Overall Progression Free Survival | Overall PFS was defined as the time from the date of first dose of amatuximab to the date of disease progression or death due to any cause. In the absence of confirmation of death, the survival time was censored at the date of the last follow-up contact. Tumor assessments performed up to the initiation of further anticancer therapy were considered. PD as measured by Modified RECIST was defined as an increase of at least 20% in the total tumor measurement over the nadir measurement, or the appearance of one or more new lesions. | From the date of first dose of amatuximab to the date of disease progression, up to approximately 5 years |