Clinical Trials List
Protocol NumberMM-121-01-101
2011-09-29 - 2013-12-16
Phase II
Terminated6
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase 1-2 trial of MM-121 in Combination with Erlotinib in Three Groups of Patients with Non-Small Cell Lung Cancer
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Trial Applicant
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Sponsor
Merrimack Pharmaceuticals, Inc
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- JENG-SEN TSENG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 廖唯昱 Division of General Internal Medicine
- 陳冠宇 Division of General Internal Medicine
- JIN-YUAN SHIH Division of General Internal Medicine
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Peng-Chan Lin Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- kang-Yun LEE Division of Thoracic Medicine
- Shu-Min Lin Division of Thoracic Medicine
- Chun-Hua Wang Division of Thoracic Medicine
- Pai-Chien Chou Division of Thoracic Medicine
- Chih-Teng Yu Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 方文豐 Division of Thoracic Medicine
- 蘇茂昌 Division of Thoracic Medicine
- 張晃智 Division of Thoracic Medicine
- 梁深怡 Division of Thoracic Medicine
- Chia-Cheng Tseng Division of Thoracic Medicine
- 趙東瀛 Division of Thoracic Medicine
- 林孟志 Division of Thoracic Medicine
- 王瑞隆 Division of Thoracic Medicine
- 鍾聿修 Division of Thoracic Medicine
- 劉世豐 Division of Thoracic Medicine
- 王逸熙 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳鴻仁 Division of General Internal Medicine
- Chih-Yen Tu Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Non-Small Cell Lung Cancer
Objectives
Primary Phase 1 Objective:
To assess the safety of the MM-121 + erlotinib combination.
To determine the recommended Phase 2 doses of the MM-121 + erlotinib combination.
Primary Phase 2 Objective:
To estimate the Progression Free Survival (PFS) of the MM-121 + erlotinib combination in three distinct groups of patients with non-small cell lung cancer, defined as follows:
Group A: Patients whose tumors are wild type for EGFR and who have not received prior EGFR targeted therapy. This group is being studied to assess whether MM-121 enhances the intrinsic sensitivity of tumors to erlotinib.
Group B: Patients whose tumors bear EGFR activating mutations and who have not received prior EGFR targeted therapy. This group is being studied to assess whether MM-121 delays or prevents acquired resistance to erlotinib or enhances intrinsic sensitivity to erlotinib.
Group C: Patients whose tumors had responded to single agent EGFR targeted therapy
and have subsequently acquired resistance. This group is being studied to assess whether MM-121 can reverse acquired resistance to erlotinib.
Secondary Objectives:
To describe the dose limiting toxicity of the MM121 + erlotinib combination.
To determine the adverse event profile of the MM121 + erlotinib combination.
To determine the pharmacokinetic parameters and immunogenicity of the MM-121 + erlotinib combination.
To obtain an initial estimate of other key efficacy endpoints (objective response rate, disease control rate, overall survival and overall PFS) in this population for use in planning subsequent randomized phase 2/3 trials.
To gather exploratory clinical data on a potentially predictive set of biomarkers to be measured in serum and tumor tissue
Test Drug
MM-121(SAR256212)
Active Ingredient
MM-121
Dosage Form
vial
Dosage
25 mg/ml
Endpoints
Primary Phase 2 Objective:
To estimate the Progression Free Survival (PFS) of the MM-121 + erlotinib combination in three distinct groups of patients with non-small cell lung cancer, defined as follows:
Secondary Objectives:
To describe the dose limiting toxicity of the MM121 + erlotinib combination.
To determine the adverse event profile of the MM121 + erlotinib combination.
To determine the pharmacokinetic parameters and immunogenicity of the MM-121 + erlotinib combination.
To obtain an initial estimate of other key efficacy endpoints (objective response rate, disease control rate, overall survival and overall PFS) in this population for use in planning subsequent randomized phase 2/3 trials.
To gather exploratory clinical data on a potentially predictive set of biomarkers to be measured in serum and tumor tissue.
To estimate the Progression Free Survival (PFS) of the MM-121 + erlotinib combination in three distinct groups of patients with non-small cell lung cancer, defined as follows:
Secondary Objectives:
To describe the dose limiting toxicity of the MM121 + erlotinib combination.
To determine the adverse event profile of the MM121 + erlotinib combination.
To determine the pharmacokinetic parameters and immunogenicity of the MM-121 + erlotinib combination.
To obtain an initial estimate of other key efficacy endpoints (objective response rate, disease control rate, overall survival and overall PFS) in this population for use in planning subsequent randomized phase 2/3 trials.
To gather exploratory clinical data on a potentially predictive set of biomarkers to be measured in serum and tumor tissue.
Inclution Criteria
Three groups of NSCLC patients are eligible for this study. In order to be considered for inclusion, subjects must meet the criteria of one of these groups:
Group A:
The subject must have a tumor with a mutation status of the EGFR tyrosine kinase domain that is wild-type. The subject’s cancer must have recurred or progressed following at least
one chemotherapy-containing regimen in the metastatic setting that is considered standard of care for NSCLC. This would include chemotherapy regimens that also contain biologic
agents such as bevacizumab or cetuximab; OR,
Group B: The subject must have a tumor with a known activating mutation of the EGFR tyrosine kinase domain. The subject must not have received any prior EGFR TKI therapy in the metastatic setting for NSCLC; OR,
Group C: The subject’s cancer must have demonstrated acquired resistance to EGFR TKI, as
outlined in Section 6.13.2. For such subjects, any number of prior therapies is permitted.
Following confirmation that a subject fulfills the requirements of one of these 3 groups, all subjects must meet the following criteria:
- Subjects must have histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer.
- Subjects being considered for Phase II portion of the study must have a lesion amenable to biopsy and must be willing to undergo a pre-treatment biopsy, unless both of the following conditions are met:
o Subject underwent a biopsy within 2 months prior to enrollment and has sufficient tumor tissue available.
o Subject has not had any intervening treatment since this biopsy.
- Subjects must be ≥ 18 years of age
- Subjects or their legal representatives must be able to understand and sign an informed consent.
- Subjects must have non-measurable or measurable tumor(s) for the phase 1 portion of the trial and must have measurable disease for the phase 2 portion in accordance with RECIST v 1.1.
- Subjects must have archived tumor samples available for analysis. Approximately 125µm of tumor sample is required (as FFPE blocks or prepared as slides, reference Study Manual). During the Phase 1 portion of the study, if the subject does not have archived tumor tissue available, they must be willing to undergo a biopsy prior to treatment initiation.
- Subjects must have an ECOG Performance Score (PS) of 0, 1 or 2
- Subjects must have adequate bone marrow reserves as evidenced by:
o ANC > 1,500/µl and
o Platelet count > 100,000/µl
o Hemoglobin > 9 g/dL
- Subjects must have adequate hepatic function as evidenced by:
o Serum total bilirubin ≤ 1.5 x ULN
o Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline
Phosphatase ≤ 2 x ULN (≤ 5 x ULN is acceptable if liver metastases are present; ≤ 5 x
ULN of Alkaline Phosphatase is acceptable if bone metastases are present)
- Subjects must have adequate renal function as evidenced by a serum creatinine ≤ 1.5 x ULN
- Subjects must be recovered from clinically significant effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for such subjects with known peripheral neuropathy.
- Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of study drugs (an effective form of contraception is an oral contraceptive or a double barrier method).
Group A:
The subject must have a tumor with a mutation status of the EGFR tyrosine kinase domain that is wild-type. The subject’s cancer must have recurred or progressed following at least
one chemotherapy-containing regimen in the metastatic setting that is considered standard of care for NSCLC. This would include chemotherapy regimens that also contain biologic
agents such as bevacizumab or cetuximab; OR,
Group B: The subject must have a tumor with a known activating mutation of the EGFR tyrosine kinase domain. The subject must not have received any prior EGFR TKI therapy in the metastatic setting for NSCLC; OR,
Group C: The subject’s cancer must have demonstrated acquired resistance to EGFR TKI, as
outlined in Section 6.13.2. For such subjects, any number of prior therapies is permitted.
Following confirmation that a subject fulfills the requirements of one of these 3 groups, all subjects must meet the following criteria:
- Subjects must have histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer.
- Subjects being considered for Phase II portion of the study must have a lesion amenable to biopsy and must be willing to undergo a pre-treatment biopsy, unless both of the following conditions are met:
o Subject underwent a biopsy within 2 months prior to enrollment and has sufficient tumor tissue available.
o Subject has not had any intervening treatment since this biopsy.
- Subjects must be ≥ 18 years of age
- Subjects or their legal representatives must be able to understand and sign an informed consent.
- Subjects must have non-measurable or measurable tumor(s) for the phase 1 portion of the trial and must have measurable disease for the phase 2 portion in accordance with RECIST v 1.1.
- Subjects must have archived tumor samples available for analysis. Approximately 125µm of tumor sample is required (as FFPE blocks or prepared as slides, reference Study Manual). During the Phase 1 portion of the study, if the subject does not have archived tumor tissue available, they must be willing to undergo a biopsy prior to treatment initiation.
- Subjects must have an ECOG Performance Score (PS) of 0, 1 or 2
- Subjects must have adequate bone marrow reserves as evidenced by:
o ANC > 1,500/µl and
o Platelet count > 100,000/µl
o Hemoglobin > 9 g/dL
- Subjects must have adequate hepatic function as evidenced by:
o Serum total bilirubin ≤ 1.5 x ULN
o Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline
Phosphatase ≤ 2 x ULN (≤ 5 x ULN is acceptable if liver metastases are present; ≤ 5 x
ULN of Alkaline Phosphatase is acceptable if bone metastases are present)
- Subjects must have adequate renal function as evidenced by a serum creatinine ≤ 1.5 x ULN
- Subjects must be recovered from clinically significant effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for such subjects with known peripheral neuropathy.
- Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of study drugs (an effective form of contraception is an oral contraceptive or a double barrier method).
Exclusion Criteria
Exclusion Criteria
- History of any second malignancy (recurrence of initial diagnosis) in the last 5 years. Subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years.
- Subjects who are pregnant or lactating .
- Subjects with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, subjects with tumor fever may be enrolled.)
- Subjects with untreated and/or symptomatic CNS malignancies (primary or metastatic); subjects with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable or tapering dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial.
- Subjects with known hypersensitivity to any of the components of MM-121 or who have had hypersensitivity reactions to fully human monoclonal antibodies.
- Subjects who have received other recent antitumor therapy including:
o Investigational therapy administered within the 30 days prior to the first scheduled day of dosing in this study.
o Any standard chemotherapy or radiation within 14 days prior to the first scheduled dose in this study. Adequate time must have passed from last treatment to first scheduled dose in this study to clear the timeframe for actual or anticipated toxicities of such treatment.
- NYHA Class III or IV congestive heart failure or LVEF < 55%. Subjects with a significant history of cardiac disease (i.e. uncontrolled blood pressure, unstable angina, myocardial infarction within 1 year or ventricular arrhythmias requiring medication) are also excluded.
- Subjects with a recent (within 1 year) cerebral vascular accident (CVA)
- Subjects with clinically significant ophthalmologic or gastrointestinal abnormalities, including: Severe dry eye syndrome; Keratoconjunctivitis sicca; Sjogren’s syndrome; Severe exposure keratopathy; Disorders that might increase the risk for epithelium-related
complications (e.g. bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis); Uncontrolled inflammatory gastrointestinal diseases (Crohn’s, ulcerative colitis, etc).
- History of allogeneic transplant (Subjects with a history of autologous bone marrow or stem cell transplant may be enrolled.)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition as erlotinib.
- Known HIV, hepatitis B or C (active, previously treated or both)
- Any other medical condition deemed by the Investigator to be likely to interfere with a subject’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
- History of any second malignancy (recurrence of initial diagnosis) in the last 5 years. Subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years.
- Subjects who are pregnant or lactating .
- Subjects with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, subjects with tumor fever may be enrolled.)
- Subjects with untreated and/or symptomatic CNS malignancies (primary or metastatic); subjects with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable or tapering dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial.
- Subjects with known hypersensitivity to any of the components of MM-121 or who have had hypersensitivity reactions to fully human monoclonal antibodies.
- Subjects who have received other recent antitumor therapy including:
o Investigational therapy administered within the 30 days prior to the first scheduled day of dosing in this study.
o Any standard chemotherapy or radiation within 14 days prior to the first scheduled dose in this study. Adequate time must have passed from last treatment to first scheduled dose in this study to clear the timeframe for actual or anticipated toxicities of such treatment.
- NYHA Class III or IV congestive heart failure or LVEF < 55%. Subjects with a significant history of cardiac disease (i.e. uncontrolled blood pressure, unstable angina, myocardial infarction within 1 year or ventricular arrhythmias requiring medication) are also excluded.
- Subjects with a recent (within 1 year) cerebral vascular accident (CVA)
- Subjects with clinically significant ophthalmologic or gastrointestinal abnormalities, including: Severe dry eye syndrome; Keratoconjunctivitis sicca; Sjogren’s syndrome; Severe exposure keratopathy; Disorders that might increase the risk for epithelium-related
complications (e.g. bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis); Uncontrolled inflammatory gastrointestinal diseases (Crohn’s, ulcerative colitis, etc).
- History of allogeneic transplant (Subjects with a history of autologous bone marrow or stem cell transplant may be enrolled.)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition as erlotinib.
- Known HIV, hepatitis B or C (active, previously treated or both)
- Any other medical condition deemed by the Investigator to be likely to interfere with a subject’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
The Estimated Number of Participants
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Taiwan
35 participants
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Global
229 participants
