Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma (MPM) (ARTEMIS)

• ClinicalTrials.gov Identifier: NCT02357147
• Recruitment Status: Terminated
• First Posted: February 6, 2015
• Results First Posted: March 17, 2020
• Last Update Posted: March 17, 2020
• Sponsor: Morphotek
• Information provided by (Responsible Party): Morphotek

Tracking Information

• First Submitted Date: January 14, 2015
• First Posted Date: February 6, 2015
• Results First Submitted Date: March 4, 2020
• Results First Posted Date: March 17, 2020
• Last Update Posted Date: March 17, 2020
• Actual Study Start Date: November 3, 2015
• Actual Primary Completion Date: November 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2020)

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 3 years ]

AEs included both non-SAEs and SAEs and the same participant can have both SAEs and as well non-SAEs.

Original Primary Outcome Measures (submitted: February 2, 2015)

Overall Survival (OS) [ Time Frame: Until date of death or up to 60 months ]

OS is defined as the time from the date of randomization to the date of death, regardless of cause.

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: February 2, 2015)

• Progression Free Survival (PFS) [ Time Frame: First observation of disease progression or until date of death or up to 60 months ]
  PFS is defined as the time (in weeks) from the date of randomization to the date of the first observation of progression as determined by the independent radiologic assessment using the modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria or the date of death, whichever comes first, regardless of the cause.
• Objective Response Rate [ORR] [ Time Frame: Until date of death or up to 60 months ]
  ORR (the proportion of subjects with complete response [CR] and partial response [PR]) as defined by the modified RECIST criteria using an independent radiologic review of computed tomography (CT)/Magnetic resonance imaging (MRI) scan. Objective response will be assessed at select visits during the Combination Treatment Phase as well as the Maintenance Treatment Phase.
• Duration of response (DR) [ Time Frame: First documentation of objective tumor progression or until date of death or up to 60 months ]
  DR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death on study (ie, within 30 days after the last dose of Test Article).
• Disease control rates (DCR) [ Time Frame: Until date of death or up to 60 months ]
  DCR is the proportion of subjects with CR, PR, or stable disease (SD) as defined by the modified RECIST criteria using an independent radiologic review of CT/MRI scan.
• Duration of disease control (DDC) [ Time Frame: First documentation of objective tumor progression or until date of death or up to 60 months ]
  DDC is defined as the time from the first documentation of objective tumor response or SD to the first documentation of objective tumor progression or to death.
• Health related quality of life (QOL) [ Time Frame: Until date of death or up to 60 months ]
  QOL as measured by the Lung Cancer Symptom Scale for mesothelioma (LCSS-Meso; Hollen, et al., 2006) as the treatment population average across the duration of the trial for 9 items.
• Duration of Performance Status Maintenance (DPSM) [ Time Frame: Until date of death or up to 60 months ]
  DPSM is defined as the time from randomization until the last time the performance status was no worse than at baseline or to death on study.
• Safety and tolerability as a measure of number of participants with Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Until date of death or up to 60 months ]
  Safety assessments will consist of monitoring and recording all adverse events, including adverse events of interest, hypersensitivity adverse events and serious adverse events; regular monitoring of hematology, blood chemistry, and urine values; regular monitoring of electrocardiograms (ECGs); periodic measurement of vital signs; and performance of physical examinations.
• Pharmacokinetic (PK) and pharmacodynamic (PD) profile [ Time Frame: Serum samples of amatuximab at Day 1 of every Cycle during the combination treatment phase and every third cycle during the maintenance treatment phase until first evidence of disease progression or up to 60 ]
  PK and PD profile is analyzed to study exposure-response relationships for effects of amatuximab on OS, PFS, ORR, DR, DCR, DDC and DPSM and hypersensitivity adverse events.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma (MPM)
• Official Title: A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Amatuximab in Combination With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Pleural Mesothelioma

Brief Summary

This study was originally designed as a multicenter, double-blind, randomized, parallel-group study, using a placebo control or amatuximab 5 milligrams per kilogram (mg/kg), administered weekly, designed to evaluate the safety and efficacy of amatuximab in combination with pemetrexed and cisplatin in participants with unresectable Malignant Pleural Mesothelioma (MPM) who have not received prior systemic therapy.

Per a business decision made by the Sponsor, participants who were randomized to amatuximab and were still on active treatment at the time of the protocol amendment may have consented to continue to receive weekly treatment with amatuximab until disease progression or intolerable toxicity at the discretion of the principal investigator. Participants randomized to placebo or who were in follow-up at the time of the amendment have been discontinued from the study.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Mesothelioma, Malignant

Intervention

• Drug: Placebo

  Combination Phase - Placebo will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

  Maintenance Phase - Placebo will be administered IV (intravenous infusion) once weekly until disease progression.

• Drug: Amatuximab

  Combination Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly for six 21-day cycles.

  Maintenance Phase - Amatuximab 5mg/kg will be administered IV (intravenous infusion) once weekly until disease progression.

• Drug: Pemetrexed
  Combination Phase - Pemetrexed 500 mg/m^2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.
• Drug: Cisplatin
  Combination Phase - Cisplatin 75 mg/m^2 will be administered IV on Day 1 of each 21-day cycle for 6 cycles.

Study Arms

• Experimental: Arm 1

  Combination Phase - Amatuximab + Pemetrexed and Cisplatin

  Maintenance Phase - Amatuximab

  Interventions:

  • Drug: Amatuximab
  • Drug: Pemetrexed
  • Drug: Cisplatin
• Experimental: Arm 2

  Combination Phase - Placebo + Pemetrexed and Cisplatin

  Maintenance Phase - Placebo

  Interventions:

  • Drug: Placebo
  • Drug: Pemetrexed
  • Drug: Cisplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 4, 2020): 124
• Original Estimated Enrollment (submitted: February 2, 2015): 610
• Actual Study Completion Date: November 30, 2018
• Actual Primary Completion Date: November 30, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Are at least 18 years of age at the time of informed consent

2. Have confirmed diagnosis of MPM with the following characteristics:

   • Unresectable disease (defined as the participant not being a candidate for curative surgery)
   • Epithelial type
   • Have an archived tissue sample to be submitted either as a formalin fixed paraffin-embedded (FFPE) tumor block, or 5 to 15 unstained slides
3. Have measurable disease at Screening by computed tomography (CT) (or magnetic resonance imaging [MRI]) as defined by at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to the modified RECIST criteria
4. Have other significant medical conditions well-controlled and stable in the opinion of the investigator for at least 30 days prior to Day 1
5. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 at Screening
6. Have a life expectancy of at least 3 months, as estimated by the investigator

7. Have adequate organ reserve as determined by laboratory test results obtained within 2 weeks prior to Study Day 1 as indicated below:

   • Absolute neutrophil count greater than or equal to 1.5 x 10^9/L
   • Platelet count greater than or equal to 100 x 10^9/L
   • Hemoglobin greater than or equal to 9 g/dL
   • Serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (Participants with serum bilirubin abnormalities greater than this specified limit are eligible only if they have known Gilberts disease)
   • Aspartate aminotransferase less than or equal to 3 x ULN
   • Alanine aminotransferase less than or equal to 3 x ULN
   • Alkaline phosphatase less than or equal to 3 x ULN
8. Have a calculated serum creatinine clearance greater than or equal to 45 mL/min using the Cockcroft-Gault equation
9. Participants of childbearing potential must be surgically sterile or consent to use a highly effective method of contraception throughout the study period. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). If a participant of childbearing potential is neither surgically sterile nor postmenopausal, highly effective contraceptive measures must start either prior to or at Screening and continue throughout the entire study period and for at least 6 months after the last dose of chemotherapy and at least 30 days after the last dose of Test Article (amatuximab or placebo) is administered (whichever is later). A highly effective method of contraception is defined as one that results in a low failure rate (that is, less than 1% per year) when used consistently and correctly. Periodic abstinence, the rhythm method, the withdrawal method, condoms, and diaphragms are not acceptable methods of contraception. Women of childbearing potential must also refrain from egg cell donation for 6 months after the final dose of investigational product
10. Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 6 months after discontinuation of chemotherapy and for 5 weeks after Test Article (amatuximab or placebo) discontinuation (whichever is later). No sperm donation is allowed during the study period and for 90 days after Test Article discontinuation
11. Be willing and able to provide written informed consent
12. Be willing and able to comply with all aspects of the protocol
13. Participants who were enrolled in the study and randomized to the amatuximab treatment arm may, at the discretion of the principle investigator (PI), consent to continue to receive amatuximab therapy until disease progression, intolerable toxicity, or withdraw of consent

Exclusion Criteria:

1. Have any history of the following:

   • Prior systemic therapy or radiotherapy for MPM; local radiotherapy of noncurative intent (ie, for prevention of instrument-tract recurrence and/or symptom control) is permitted
   • Evidence of other active, invasive malignancy requiring treatment within the past 5 years; noninvasive cancer history (such as carcinoma-in-situ [CIS] that has been resected) is allowed
2. Currently have mesothelioma of the sarcomatous type, mixed histologic disease, or have malignant peritoneal mesothelioma
3. Have confirmed presence of central nervous system metastases
4. Active viral hepatitis or active human immunodeficiency virus infection
5. Have evidence of any other serious systemic disease, including active bacterial or fungal infection, or any medical condition that, in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
6. Clinically significant heart disease (eg, congestive heart failure of New York Heart Association Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 months)
7. Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: participants with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible). A clinically significant ECG abnormality, including a marked prolonged QT/QTc interval (eg, a repeated demonstration of a QTc interval of greater than 500 ms)
8. Have known intolerance to the Test Article (ie, documented hypersensitivity AE to prior monoclonal antibody therapy, or to amatuximab or any of its excipients)
9. Pregnant and/or lactating females are excluded; a negative beta-human chorionic gonadotropin [B-hCG]) is required during Screening, and a separate local assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of Test Article
10. Have any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
11. Are scheduled for debulking surgery during the study
12. Are currently enrolled in another clinical study or used any investigational drug or device within 30 days (or 5 x the half-life of the investigational drug/device, whichever is longer) preceding informed consent
13. Participants previously randomized to placebo
14. Participants who have not signed the updated informed consent form associated with this amendment 2
15. Participants who have radiographic or clinical disease progression or intolerable toxicity such that ongoing amatuximab treatment through this study is not appropriate

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, France, Germany, Italy, United Kingdom, United States

Administrative Information

• NCT Number: NCT02357147
• Other Study ID Numbers: MORAb-009-201; 2014-004489-85 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Morphotek
• Original Responsible Party: Same as current
• Current Study Sponsor: Morphotek
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Morphotek
• Verification Date: February 2017