Clinical Trials List
Protocol NumberCP-MGAH22-05
NCT Number(ClinicalTrials.gov Identfier)NCT02689284
2016-12-01 - 2021-05-31
Phase I/II
Terminated3
ICD-10D00.2
Carcinoma in situ of stomach
ICD-10C16
Malignant neoplasm of stomach
ICD-9230.2
Carcinoma in situ of stomach
A Phase 1b/2, Open Label, Dose Escalation Study of Margetuximab in Combination with Pembrolizumab in Patients with Treatment-Naïve (locally advanced) or Relapsed/Refractory Advanced HER2+ Gastroesophageal Junction or Gastric Cancer
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
MacroGenics, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chung-Pin Li Digestive System Department
- Yi-Ping Hung Division of Hematology & Oncology
- Rheun-Chuan Lee Division of Radiology
The Actual Total Number of Participants Enrolled
1 Completed
Audit
None
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Ann-Lii Cheng 無
- Chia-Chi Lin 無
- TA-CHEN HUANG 無
- 陳國興 無
- 詹德全 Division of General Surgery
- SUNG-HSIN KUO 無
- 張端瑩 無
- Hsiang-Fong Kao 無
- 葉人華 Division of Hematology & Oncology
- Chih-Hung Hsu 無
- 林宗哲 無
- 呂理駿 無
- 梁逸歆 無
- 張浩銘 Division of General Surgery
- Chiun Hsu 無
- 林育麟 無
- YU-YUN SHAO 無
- 陳佳宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
Relapsed/Refractory Advanced HER2+ Gastroesophageal Junction or Gastric Cancer
Objectives
The primary objectives of this study are: To characterize the safety, tolerability, dose-limiting toxicities (DLT), and maximum tolerateddose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximabwhen administered intravenously (IV) every 3 weeks in combination with 200 mg pembrolizumabadministered IV every 3 weeks to patients with relapsed/refractory unresectable locally advancedor metastatic HER2+ GEJ or gastric cancer. To investigate the preliminary anti-tumor activity, as measured by objective response rate (ORR)and response duration, of margetuximab when administered IV every 3 weeks in combination withpembrolizumab administered IV every 3 weeks using both conventional Response EvaluationCriteria in Solid Tumors (RECIST) 1.1 (Protocol, Appendix 7) and immune-related responsecriteria (irRC) (Protocol, Appendix 8).Secondary objective of this study are: To investigate the preliminary effect on overall survival (OS) and progression-free survival (PFS)of margetuximab administered IV every 3 weeks in combination with pembrolizumabadministered IV every 3 weeks. To characterize the pharmacodynamic (PD) activity of margetuximab when administered IV every3 weeks in combination with pembrolizumab administered IV every 3 weeks. To characterize the pharmacokinetics (PK) and immunogenicity of margetuximab administered IVevery 3 weeks in combination with pembrolizumab administered IV every 3 weeks.
Test Drug
Margetuximab
Active Ingredient
Margetuximab
Dosage Form
Injection
Dosage
25
Endpoints
Safety Assessments:
The safety assessment will be based on the evaluation of treatment-emergent AEs that occur from
the time of initiation of administration of either study drug through the End of Treatment Visit or
28 days after the last dose of study drug (whichever is later) and will be determined based on
signs, symptoms, physical examination findings and/or laboratory test results from enrolled
patients as appropriate
AEs and serious adverse events (SAEs) will be collected from the time the patient receives the
first dose of study drug until the End of Treatment Visit or 28 days after the last dose of study
drug (whichever is later). Protocol-related AEs and SAEs will be collected from the time the
patient has consented to study participation.
AEs reported between the time the patient signed the informed consent and the administration of
the first dose of study drug will be captured as medical history.
SAEs considered related to study drug may be reported at any time, even after the patient’s final
visit.
Progression of the underlying neoplasm resulting in hospitalization or death (e.g., patient
hospitalized for or dies from PD only, without any other SAE) will be documented as an antitumor
activity outcome and not as an SAE. If an SAE occurs in a patient and it is unclear whether the
event is related to PD, the SAE should be reported.
The reporting of laboratory/vital signs abnormalities as both laboratory findings and AEs should
be avoided. They should not be reported as AEs unless any one of the following are met:
o Any criterion for an SAE is fulfilled
o The laboratory/vital signs abnormality causes the patient to discontinue from the study
treatment
o The laboratory/vital signs abnormality causes the patient to interrupt the study treatment
o The laboratory/vital signs abnormality requires intervention
o The laboratory/vital signs are deemed clinically significant, based on medical judgment.
Efficacy Assessments:
Tumor assessments will be obtained at screening using CT and/or MRI scans at time intervals as specified in
Protocol, Appendix 1 (Time and Events Table: Dose Escalation) and Protocol, Appendix 2 (Time and Events
Schedule: Dose Expansion). Radiographic disease assessments will occur every 6 weeks (i.e., following 2
cycles of treatment [Cycles 3, 5, etc.]) for the first 24 weeks and then every twelve (12) weeks thereafter until
documented progression, initiation of alternative anti-cancer therapy, lost to follow up, withdrawal of informed
consent, death, or end of study. Treatment will continue until patients have completed study therapy and
required follow-up, experienced disease progression according to irRC, or have been withdrawn from the study.
At each on-treatment tumor assessment time point, the objective response status will be determined.
For patients who demonstrate acceptable tolerability of treatment with pembrolizumab and margetuximab and
achieve an objective response assessment of irCR, irPR or irSD, or unconfirmed clinically-stable irPD, therapy
may be continued
The safety assessment will be based on the evaluation of treatment-emergent AEs that occur from
the time of initiation of administration of either study drug through the End of Treatment Visit or
28 days after the last dose of study drug (whichever is later) and will be determined based on
signs, symptoms, physical examination findings and/or laboratory test results from enrolled
patients as appropriate
AEs and serious adverse events (SAEs) will be collected from the time the patient receives the
first dose of study drug until the End of Treatment Visit or 28 days after the last dose of study
drug (whichever is later). Protocol-related AEs and SAEs will be collected from the time the
patient has consented to study participation.
AEs reported between the time the patient signed the informed consent and the administration of
the first dose of study drug will be captured as medical history.
SAEs considered related to study drug may be reported at any time, even after the patient’s final
visit.
Progression of the underlying neoplasm resulting in hospitalization or death (e.g., patient
hospitalized for or dies from PD only, without any other SAE) will be documented as an antitumor
activity outcome and not as an SAE. If an SAE occurs in a patient and it is unclear whether the
event is related to PD, the SAE should be reported.
The reporting of laboratory/vital signs abnormalities as both laboratory findings and AEs should
be avoided. They should not be reported as AEs unless any one of the following are met:
o Any criterion for an SAE is fulfilled
o The laboratory/vital signs abnormality causes the patient to discontinue from the study
treatment
o The laboratory/vital signs abnormality causes the patient to interrupt the study treatment
o The laboratory/vital signs abnormality requires intervention
o The laboratory/vital signs are deemed clinically significant, based on medical judgment.
Efficacy Assessments:
Tumor assessments will be obtained at screening using CT and/or MRI scans at time intervals as specified in
Protocol, Appendix 1 (Time and Events Table: Dose Escalation) and Protocol, Appendix 2 (Time and Events
Schedule: Dose Expansion). Radiographic disease assessments will occur every 6 weeks (i.e., following 2
cycles of treatment [Cycles 3, 5, etc.]) for the first 24 weeks and then every twelve (12) weeks thereafter until
documented progression, initiation of alternative anti-cancer therapy, lost to follow up, withdrawal of informed
consent, death, or end of study. Treatment will continue until patients have completed study therapy and
required follow-up, experienced disease progression according to irRC, or have been withdrawn from the study.
At each on-treatment tumor assessment time point, the objective response status will be determined.
For patients who demonstrate acceptable tolerability of treatment with pembrolizumab and margetuximab and
achieve an objective response assessment of irCR, irPR or irSD, or unconfirmed clinically-stable irPD, therapy
may be continued
Inclution Criteria
Inclusion Criteria:
General
1. Ability to provide informed consent and documentation of informed consent prior to initiation of
any study-related tests or procedures that are not part of standard-of-care for the patient’s disease.
Patients must also be willing and able to comply with study procedures, including the acquisition of
specified research specimens.
2. Age ≥ 18 years old.
3. Histologically-proven unresectable locally advanced or metastatic HER2+ gastroesophageal
junction (GEJ) or gastric adenocarcinoma determined as 3+ by immunohistochemistry (IHC) or in
situ hybridization (ISH)-amplified (as per College of American Pathologists/American Society of
Clinical Oncology Guidelines).
4. Have received prior treatment with trastuzumab.
5. Have received treatment with at least one or more lines of cytotoxic chemotherapy in the
metastatic setting. Prior adjuvant therapy that resulted in relapse within 6 months of completion of
therapy will be considered a line of treatment for metastatic disease. Eligible patients must have
progressed on, or following, the most recent line of therapy.
a. In Dose Expansion Phase, only one prior line of treatment that includes trastuzumab is
allowed.
6. Resolution of all chemotherapy or radiation-related toxicities to ≤ Grade 1 (with exception of ≤
Grade 2 alopecia, stable sensory neuropathy, or stable electrolyte disturbances that are managed
by supplementation).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Protocol, Appendix
6)
8. Life expectancy ≥ 12 weeks.
9. Measurable disease as per RECIST 1.1 criteria (Protocol, Appendix 7) and documented by
computed tomography (CT) and/or magnetic resonance imaging (MRI). Patients with evaluable
disease only will not be enrolled on this study. Note: Lesions to be used as measurable disease for
the purpose of response assessment must either a) not reside in a field that has been subjected to
prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the
completion of prior radiotherapy and prior to study enrollment.
10. Patients should have a formalin-fixed, paraffin embedded tumor specimen or unstained slides
identified and available for analysis, to enable determination of the expression of HER2 and
programmed death ligand 1 (PD-L1) within tumor specimens using IHC staining.
Laboratory Features
11. Acceptable laboratory parameters as follows:
a. Platelet count 100 × 103
/µL without transfusion within 2 weeks prior to the initiation of
study drug.
b. Absolute neutrophil count (ANC) 1.5 × 103
/ µL in the absence of any growth factor support
within 2 weeks prior to the initiation of study drug.
c. Hemoglobin (Hgb) 9 g/dL
d. ALT/AST 3.0 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5 × ULN
e. Total bilirubin 1.5 × ULN, except patients with Gilbert’s syndrome, who may enroll if the
conjugated bilirubin is within normal limits.
f. Creatinine < 2 mg/dL, or a calculated or measured creatinine clearance > 50 mL/min.
Reproductive Features
12. Female patients of childbearing potential (not surgically sterilized and between menarche and 1
year postmenopause) must have a negative urine pregnancy test performed within 72 hours prior
to the initiation of study drug administration. Further, female patients of childbearing potential
must agree to use highly effective contraceptive measures from the time of consent through 120
days after discontinuation of study drug administration.
13. Male patients with partners of childbearing potential must use barrier contraception. In addition,
male patients should also have their partners use another method of contraception from the time of
consent through 120 days after discontinuation of study drug administration.
14. Is not pregnant or breastfeeding, or expecting to conceive or father children within the projected
duration of the trial, starting with the prescreening or screening visit through 120 days after the
last dose of trial treatment.
Tumor Biopsy
15. At least 20 of the 60 patients enrolled in the Cohort Expansion Phase (approximately 10 from each
region [North America and Asia]) must have one lesion considered to be potentially accessible to
biopsy and be willing to provide consent for biopsy samples. An attempt at a tumor biopsy of
locally accessible lesions will be made for at least 20 of the 60 patients. Tumor lesions used for
biopsy should not be lesions used as RECIST target lesions unless there are no other lesions
suitable for biopsy. If a RECIST target lesion is used for biopsy the lesion must be ≥ 2 cm in
longest diameter. Tumor biopsies should only be obtained from lesions that are felt to be
accessible with acceptable clinical risk in the judgment of the investigator.
Previous Checkpoint Inhibitor Therapy
16. Patients who have previously received an immune checkpoint inhibitor (e.g., programmed-death
ligand 1 antibody [anti-PD-L1], programmed cell death protein 1 antibody [anti-PD-1], cytotoxic
T-lymphocyte-associated protein 4 antibody [anti-CTLA-4]) prior to enrollment must have
toxicities related to the checkpoint inhibitor resolved to ≤ Grade 1 or baseline (prior to the
checkpoint inhibitor) to be eligible for enrollment.
General
1. Ability to provide informed consent and documentation of informed consent prior to initiation of
any study-related tests or procedures that are not part of standard-of-care for the patient’s disease.
Patients must also be willing and able to comply with study procedures, including the acquisition of
specified research specimens.
2. Age ≥ 18 years old.
3. Histologically-proven unresectable locally advanced or metastatic HER2+ gastroesophageal
junction (GEJ) or gastric adenocarcinoma determined as 3+ by immunohistochemistry (IHC) or in
situ hybridization (ISH)-amplified (as per College of American Pathologists/American Society of
Clinical Oncology Guidelines).
4. Have received prior treatment with trastuzumab.
5. Have received treatment with at least one or more lines of cytotoxic chemotherapy in the
metastatic setting. Prior adjuvant therapy that resulted in relapse within 6 months of completion of
therapy will be considered a line of treatment for metastatic disease. Eligible patients must have
progressed on, or following, the most recent line of therapy.
a. In Dose Expansion Phase, only one prior line of treatment that includes trastuzumab is
allowed.
6. Resolution of all chemotherapy or radiation-related toxicities to ≤ Grade 1 (with exception of ≤
Grade 2 alopecia, stable sensory neuropathy, or stable electrolyte disturbances that are managed
by supplementation).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Protocol, Appendix
6)
8. Life expectancy ≥ 12 weeks.
9. Measurable disease as per RECIST 1.1 criteria (Protocol, Appendix 7) and documented by
computed tomography (CT) and/or magnetic resonance imaging (MRI). Patients with evaluable
disease only will not be enrolled on this study. Note: Lesions to be used as measurable disease for
the purpose of response assessment must either a) not reside in a field that has been subjected to
prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the
completion of prior radiotherapy and prior to study enrollment.
10. Patients should have a formalin-fixed, paraffin embedded tumor specimen or unstained slides
identified and available for analysis, to enable determination of the expression of HER2 and
programmed death ligand 1 (PD-L1) within tumor specimens using IHC staining.
Laboratory Features
11. Acceptable laboratory parameters as follows:
a. Platelet count 100 × 103
/µL without transfusion within 2 weeks prior to the initiation of
study drug.
b. Absolute neutrophil count (ANC) 1.5 × 103
/ µL in the absence of any growth factor support
within 2 weeks prior to the initiation of study drug.
c. Hemoglobin (Hgb) 9 g/dL
d. ALT/AST 3.0 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5 × ULN
e. Total bilirubin 1.5 × ULN, except patients with Gilbert’s syndrome, who may enroll if the
conjugated bilirubin is within normal limits.
f. Creatinine < 2 mg/dL, or a calculated or measured creatinine clearance > 50 mL/min.
Reproductive Features
12. Female patients of childbearing potential (not surgically sterilized and between menarche and 1
year postmenopause) must have a negative urine pregnancy test performed within 72 hours prior
to the initiation of study drug administration. Further, female patients of childbearing potential
must agree to use highly effective contraceptive measures from the time of consent through 120
days after discontinuation of study drug administration.
13. Male patients with partners of childbearing potential must use barrier contraception. In addition,
male patients should also have their partners use another method of contraception from the time of
consent through 120 days after discontinuation of study drug administration.
14. Is not pregnant or breastfeeding, or expecting to conceive or father children within the projected
duration of the trial, starting with the prescreening or screening visit through 120 days after the
last dose of trial treatment.
Tumor Biopsy
15. At least 20 of the 60 patients enrolled in the Cohort Expansion Phase (approximately 10 from each
region [North America and Asia]) must have one lesion considered to be potentially accessible to
biopsy and be willing to provide consent for biopsy samples. An attempt at a tumor biopsy of
locally accessible lesions will be made for at least 20 of the 60 patients. Tumor lesions used for
biopsy should not be lesions used as RECIST target lesions unless there are no other lesions
suitable for biopsy. If a RECIST target lesion is used for biopsy the lesion must be ≥ 2 cm in
longest diameter. Tumor biopsies should only be obtained from lesions that are felt to be
accessible with acceptable clinical risk in the judgment of the investigator.
Previous Checkpoint Inhibitor Therapy
16. Patients who have previously received an immune checkpoint inhibitor (e.g., programmed-death
ligand 1 antibody [anti-PD-L1], programmed cell death protein 1 antibody [anti-PD-1], cytotoxic
T-lymphocyte-associated protein 4 antibody [anti-CTLA-4]) prior to enrollment must have
toxicities related to the checkpoint inhibitor resolved to ≤ Grade 1 or baseline (prior to the
checkpoint inhibitor) to be eligible for enrollment.
Exclusion Criteria
Exclusion Criteria:
1. Patients with symptomatic central nervous system (CNS) metastases must have been treated, be
asymptomatic, and meet the following at the time of enrollment:
a. No concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg
prednisone/day or equivalent)
b. No progression of CNS metastases on MRI or CT for at least 21 days after last day of prior
therapy for the CNS metastases
c. No concurrent leptomeningeal disease or cord compression
2. Patients who experienced the following immune checkpoint inhibitor-related AEs (i.e., the
following AEs make the patient ineligible despite the AE resolving to ≤ Grade 1 or baseline):
a. ≥ Grade 3 ocular AE
b. Changes in liver function tests that met the criteria for Hy’s Law (> 3 × ULN of either
ALT/AST with concurrent > 2 × ULN of total bilirubin and without alternate etiology)
c. ≥ Grade 3 neurologic toxicity
d. ≥ Grade 3 colitis or pneumonitis
3. Patients with any history of known or suspected autoimmune disease with the specific exceptions
of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within
the past 2 years), and patients with a history of autoimmune disease that are now clinically stable
with replacement therapy and by laboratory testing.
a. Patients with history of psoriatic arthritis are excluded.
4. History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
5. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks
prior to the initiation of study drug administration. Adjuvant hormonal therapy for treatment of
prostate or breast cancer is allowed.
6. Treatment with radiation therapy within 3 weeks prior to the initiation of study drug
administration.
7. Treatment with corticosteroids (≥ 10 mg per day prednisone or equivalent) or other immune
suppressive drugs within the 14 days prior to the initiation of study drug administration. Steroids
for topical, ophthalmic, inhaled or nasal administration are allowed.
8. History of clinically-significant cardiovascular disease including but not limited to:
a. Myocardial infarction or unstable angina within the 6 months prior to the initiation of study
drug.
b. Stroke or transient ischemic attack within 6 months prior to the initiation of study drug.
c. Clinically-significant cardiac arrhythmias.
d. Uncontrolled hypertension: systolic blood pressure (SBP) >180 mmHg, diastolic blood
pressure (DBP) >100 mmHg.
e. Congestive heart failure (New York Heart Association [NYHA] class III-IV).
f. Pericarditis or clinically significant pericardial effusion.
g. Myocarditis.
h. Left ventricle ejection fraction (LVEF) < 50% by echocardiogram or multi-gated acquisition
(MUGA) scan.
9. Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen
use to maintain adequate oxygenation.
10. Presence of active pneumonitis
11. Clinically-significant gastrointestinal disorders including:
a. Any history of gastrointestinal perforation unless the affected area has been deemed by the
investigator to no longer be a risk for perforation.
b. History of clinically significant gastrointestinal bleeding within 4 weeks prior to the initiation
of study drug.
c. History of acute pancreatitis within 4 weeks prior to the initiation of study drug
d. Diverticulitis that is clinically significant in the opinion of the investigator based on the extent
or severity of known disease and/or the occurrence of clinically-significant disease flares
within 4 weeks prior to the initiation of study drug administration.
12. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment
within 7 days prior to the initiation of study drug. Patients requiring any systemic antiviral,
antifungal, or antibacterial therapy for active infection must have completed treatment no less than
one week prior to the initiation of study drug.
13. Known positive testing for human immunodeficiency virus or history of acquired immune
deficiency syndrome.
14. Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface
antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR).
15. No history of another malignancy or a concurrent malignancy. Exceptions include patients who
have been disease free for two years, or successfully treated for non-melanoma skin cancer,
localized prostate cancer (Gleason Score <6) or carcinoma in situ, for example cervical cancer in
situ, are eligible.
16. History of trauma or major surgery within 4 weeks prior to the initiation of study drug
administration.
17. Any serious underlying medical or psychiatric condition that would impair the ability of the
patient to receive or tolerate the planned treatment at the investigational site.
18. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the
drug or vehicle formulation for margetuximab or pembrolizumab (Protocol, Section 6.1).
19. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug
administration. Inactivated annual influenza vaccination is allowed.
20. Female patient who is breastfeeding. Is pregnant or breastfeeding, or expecting to conceive or
father children within the projected duration of the trial, starting with the screening visit through
120 days after the last dose of trial treatment.
21. Dementia or altered mental status that would preclude understanding and rendering of informed
consent.
22. Employees of MacroGenics, Inc and Merck & Co., Inc. unless approved by institutional review
board (IRB) and principal investigator.
23. Prisoners or other individuals who are involuntarily detained.
24. Any issue that in the opinion of the investigator, would contraindicate the patient’s participation in
the study or confound the results of the study.
1. Patients with symptomatic central nervous system (CNS) metastases must have been treated, be
asymptomatic, and meet the following at the time of enrollment:
a. No concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg
prednisone/day or equivalent)
b. No progression of CNS metastases on MRI or CT for at least 21 days after last day of prior
therapy for the CNS metastases
c. No concurrent leptomeningeal disease or cord compression
2. Patients who experienced the following immune checkpoint inhibitor-related AEs (i.e., the
following AEs make the patient ineligible despite the AE resolving to ≤ Grade 1 or baseline):
a. ≥ Grade 3 ocular AE
b. Changes in liver function tests that met the criteria for Hy’s Law (> 3 × ULN of either
ALT/AST with concurrent > 2 × ULN of total bilirubin and without alternate etiology)
c. ≥ Grade 3 neurologic toxicity
d. ≥ Grade 3 colitis or pneumonitis
3. Patients with any history of known or suspected autoimmune disease with the specific exceptions
of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within
the past 2 years), and patients with a history of autoimmune disease that are now clinically stable
with replacement therapy and by laboratory testing.
a. Patients with history of psoriatic arthritis are excluded.
4. History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
5. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks
prior to the initiation of study drug administration. Adjuvant hormonal therapy for treatment of
prostate or breast cancer is allowed.
6. Treatment with radiation therapy within 3 weeks prior to the initiation of study drug
administration.
7. Treatment with corticosteroids (≥ 10 mg per day prednisone or equivalent) or other immune
suppressive drugs within the 14 days prior to the initiation of study drug administration. Steroids
for topical, ophthalmic, inhaled or nasal administration are allowed.
8. History of clinically-significant cardiovascular disease including but not limited to:
a. Myocardial infarction or unstable angina within the 6 months prior to the initiation of study
drug.
b. Stroke or transient ischemic attack within 6 months prior to the initiation of study drug.
c. Clinically-significant cardiac arrhythmias.
d. Uncontrolled hypertension: systolic blood pressure (SBP) >180 mmHg, diastolic blood
pressure (DBP) >100 mmHg.
e. Congestive heart failure (New York Heart Association [NYHA] class III-IV).
f. Pericarditis or clinically significant pericardial effusion.
g. Myocarditis.
h. Left ventricle ejection fraction (LVEF) < 50% by echocardiogram or multi-gated acquisition
(MUGA) scan.
9. Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen
use to maintain adequate oxygenation.
10. Presence of active pneumonitis
11. Clinically-significant gastrointestinal disorders including:
a. Any history of gastrointestinal perforation unless the affected area has been deemed by the
investigator to no longer be a risk for perforation.
b. History of clinically significant gastrointestinal bleeding within 4 weeks prior to the initiation
of study drug.
c. History of acute pancreatitis within 4 weeks prior to the initiation of study drug
d. Diverticulitis that is clinically significant in the opinion of the investigator based on the extent
or severity of known disease and/or the occurrence of clinically-significant disease flares
within 4 weeks prior to the initiation of study drug administration.
12. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment
within 7 days prior to the initiation of study drug. Patients requiring any systemic antiviral,
antifungal, or antibacterial therapy for active infection must have completed treatment no less than
one week prior to the initiation of study drug.
13. Known positive testing for human immunodeficiency virus or history of acquired immune
deficiency syndrome.
14. Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface
antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR).
15. No history of another malignancy or a concurrent malignancy. Exceptions include patients who
have been disease free for two years, or successfully treated for non-melanoma skin cancer,
localized prostate cancer (Gleason Score <6) or carcinoma in situ, for example cervical cancer in
situ, are eligible.
16. History of trauma or major surgery within 4 weeks prior to the initiation of study drug
administration.
17. Any serious underlying medical or psychiatric condition that would impair the ability of the
patient to receive or tolerate the planned treatment at the investigational site.
18. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the
drug or vehicle formulation for margetuximab or pembrolizumab (Protocol, Section 6.1).
19. Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug
administration. Inactivated annual influenza vaccination is allowed.
20. Female patient who is breastfeeding. Is pregnant or breastfeeding, or expecting to conceive or
father children within the projected duration of the trial, starting with the screening visit through
120 days after the last dose of trial treatment.
21. Dementia or altered mental status that would preclude understanding and rendering of informed
consent.
22. Employees of MacroGenics, Inc and Merck & Co., Inc. unless approved by institutional review
board (IRB) and principal investigator.
23. Prisoners or other individuals who are involuntarily detained.
24. Any issue that in the opinion of the investigator, would contraindicate the patient’s participation in
the study or confound the results of the study.
The Estimated Number of Participants
-
Taiwan
9 participants
-
Global
72 participants
