Clinical Trials List
Protocol NumberSym015-01
NCT Number(ClinicalTrials.gov Identfier)NCT02648724
2017-04-25 - 2019-12-31
Others
Recruiting2
Terminated3
ICD-10C34
Malignant neoplasm of bronchus and lung
An Open-label, Multicenter Phase 1a/2a Trial Investigating the Safety, Tolerability and Antitumor Activity of Multiple Doses of Sym015, a Monoclonal Antibody Mixture Targeting MET, in Patients with Advanced Solid Tumor Malignancies
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Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Li-Yuan Bai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 黃子權 Division of Hematology & Oncology
- 蔡文銓 Division of Hematology & Oncology
- 張平穎 Division of Hematology & Oncology
- 葉人華 Division of Hematology & Oncology
- 陳宇欽 Division of Hematology & Oncology
- 吳宜穎 Division of Hematology & Oncology
- 戴明燊 Division of Hematology & Oncology
- 戴明桑 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wen-Pin Su Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 陳焜結 Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- MING-CHE LIU Division of Hematology & Oncology
- CHIN-SHENG HUNG Division of Hematology & Oncology
- Chi-Li Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
solid tumor
Objectives
Primary objective of Part 1, Dose-Escalation: To assess the safety and tolerability
of Sym015 when administered by intravenous (IV) infusion on a Q2W schedule to
patients with KRAS WT advanced solid tumor malignancies without available
therapeutic options.
Primary objective of Part 2: To evaluate the antitumor activity of Sym015 when
administered at the Q2W RP2D to patients with MET-amplified, KRAS WT solid
tumor malignancies without available therapeutic options.
Test Drug
Sym015
Active Ingredient
Sym015
Dosage Form
Injection
Dosage
18mg/kg，12mg/kg
Endpoints
Primary Endpoint of Part 1, Dose-Escalation: The occurrence of dose-limiting
toxicities (DLT) measured during Cycle 1 of Sym015 administration on a Q2W
(28 days equals 1 cycle) dosing schedule.
Primary Endpoint of Part 2: Documented objective response (OR) (defined as
partial response [PR] or complete response [CR]) in the Basket Cohort, assessed
by the Response Evaluation Criteria in Solid Tumors (Version 1.1) (RECIST v1.1)
at any time during trial participation by Investigator assessment.
toxicities (DLT) measured during Cycle 1 of Sym015 administration on a Q2W
(28 days equals 1 cycle) dosing schedule.
Primary Endpoint of Part 2: Documented objective response (OR) (defined as
partial response [PR] or complete response [CR]) in the Basket Cohort, assessed
by the Response Evaluation Criteria in Solid Tumors (Version 1.1) (RECIST v1.1)
at any time during trial participation by Investigator assessment.
Inclution Criteria
1. Written informed consent given before any trial-specific procedure is initiated
2. Male or female, at least 20 years of age at the time of informed consent
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
4. Life expectancy >3 months assessed during Screening
5. Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available or accessible (i.e. patients must have recurrent and/or progressive disease and be without other therapeutic options)
6. Tumor documented to be KRAS WT by local assessment according to institutional standards. If KRAS WT is not previously documented and if archival tissue is not available for pretrial assessment, patient must be willing to undergo a tumor biopsy to confirm eligibility
7. Part 2 ONLY:
a. Measurable disease according to the RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to C1/D1
Note: Measurable disease is defined as 1 or more target lesions assessed by CT or MRI. A tumor lesion situated in a previously irradiated area is considered measurable only if subsequent PD has been documented in the lesion
b. Tumor documented to be KRAS WT by local assessment according to institutional standards.
Note: Peripheral blood collection for KRAS-mutation assessment in ctDNA will be allowed as a local pre-screening methodology by Guardant360* analysis. Other liquid biopsy methodologies, except if used to detect METex14 mutation, will only be allowed if previously approved by the Sponsor.
c. Basket Cohort ONLY:
• Confirmed MET-amplification by local assessment; i.e. gene [G]-to-copy number [CN] control probe ratio [G:CN] >2.2 scored in 50 tumor nuclei by FISH, chromogenic in situ hybridization (CISH), silver in situ hybridization (SISH) or similar, or a copy number >5 by next-generation sequencing (NGS) or quantitative PCR (qPCR)
Note: Peripheral blood collection for MET-amplification assessment in ctDNA will be allowed as a local pre-screening methodology provided results are 3+ by Guardant360* analysis (or equivalent to 3+ by Guardant360 if an alternative Sponsor-approved methodology is used), and provided subsequent required confirmatory tumor tissue evaluation results meet the above inclusion criterion.
*
• No prior therapy with MET-targeting agents
Note: An exception will be a subset of approximately 6 patients entered to the Basket Cohort after having received prior therapy with a MET-targeting TKI.
• Willingness to undergo a pre- and post-dosing biopsy (maximum of 2 biopsies) from primary or metastatic tumor site(s) considered safely accessible for biopsy
d. NSCLC Cohort ONLY:
Documented METex14 mutations (patients need not be MET-amplified and may have received prior therapy with a MET-targeting TKI)
Note: Patients with malignancies other than NSCLC and with documented METex14 mutation may be considered for entry to this cohort following discussion with the Sponsor’s Medical Monitor(s).
Note: METex14 mutation status to be documented according to local institutional standards. Assessment in ctDNA by Guardant360 technology or equivalent is allowed.
Subsequent confirmation in tumor tissue is preferred but not required.
8. If female and of childbearing potential, a negative pregnancy test
9. Male or female, either not of childbearing potential or agreeing to use a medically effective method of contraception as per institutional standards during the trial and for 4 months after the last dose of trial drug
2. Male or female, at least 20 years of age at the time of informed consent
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
4. Life expectancy >3 months assessed during Screening
5. Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic, and that is refractory to standard therapy or for which no standard therapy is available or accessible (i.e. patients must have recurrent and/or progressive disease and be without other therapeutic options)
6. Tumor documented to be KRAS WT by local assessment according to institutional standards. If KRAS WT is not previously documented and if archival tissue is not available for pretrial assessment, patient must be willing to undergo a tumor biopsy to confirm eligibility
7. Part 2 ONLY:
a. Measurable disease according to the RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to C1/D1
Note: Measurable disease is defined as 1 or more target lesions assessed by CT or MRI. A tumor lesion situated in a previously irradiated area is considered measurable only if subsequent PD has been documented in the lesion
b. Tumor documented to be KRAS WT by local assessment according to institutional standards.
Note: Peripheral blood collection for KRAS-mutation assessment in ctDNA will be allowed as a local pre-screening methodology by Guardant360* analysis. Other liquid biopsy methodologies, except if used to detect METex14 mutation, will only be allowed if previously approved by the Sponsor.
c. Basket Cohort ONLY:
• Confirmed MET-amplification by local assessment; i.e. gene [G]-to-copy number [CN] control probe ratio [G:CN] >2.2 scored in 50 tumor nuclei by FISH, chromogenic in situ hybridization (CISH), silver in situ hybridization (SISH) or similar, or a copy number >5 by next-generation sequencing (NGS) or quantitative PCR (qPCR)
Note: Peripheral blood collection for MET-amplification assessment in ctDNA will be allowed as a local pre-screening methodology provided results are 3+ by Guardant360* analysis (or equivalent to 3+ by Guardant360 if an alternative Sponsor-approved methodology is used), and provided subsequent required confirmatory tumor tissue evaluation results meet the above inclusion criterion.
*
• No prior therapy with MET-targeting agents
Note: An exception will be a subset of approximately 6 patients entered to the Basket Cohort after having received prior therapy with a MET-targeting TKI.
• Willingness to undergo a pre- and post-dosing biopsy (maximum of 2 biopsies) from primary or metastatic tumor site(s) considered safely accessible for biopsy
d. NSCLC Cohort ONLY:
Documented METex14 mutations (patients need not be MET-amplified and may have received prior therapy with a MET-targeting TKI)
Note: Patients with malignancies other than NSCLC and with documented METex14 mutation may be considered for entry to this cohort following discussion with the Sponsor’s Medical Monitor(s).
Note: METex14 mutation status to be documented according to local institutional standards. Assessment in ctDNA by Guardant360 technology or equivalent is allowed.
Subsequent confirmation in tumor tissue is preferred but not required.
8. If female and of childbearing potential, a negative pregnancy test
9. Male or female, either not of childbearing potential or agreeing to use a medically effective method of contraception as per institutional standards during the trial and for 4 months after the last dose of trial drug
Exclusion Criteria
1. Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to C1/D1 except:
• Nitrosoureas and mitomycin C within 6 weeks prior to C1/D1
2. Part 2 ONLY:
a. Prior therapy with MET-inhibiting agents
Note: Exceptions will be a subset of approximately 6 patients entered to the Basket Cohort after having received prior therapy with a MET-targeting TKI, and patients entered to the NSCLC Cohort who may have received prior therapy with a METtargeting TKI.
b. Prior therapy with antibody to HGF
c. Basket Cohort ONLY: Tumor status demonstrating MET-polysomy in the absence of MET-amplification, as specified
Note: Patients in the NSCLC Cohort with polysomy are eligible
d. Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following the radiotherapy
Note: Radiotherapy for pain control against non-target lesions is allowed, as long as it does not influence bone marrow function
3. Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone equivalent) within 2 weeks prior to C1/D1 with the exception of the following allowed therapies:
a. Hormonal therapy (e.g. Megace) for appetite stimulation
b. Nasal, ophthalmic, inhaled, and topical glucocorticoid preparations
c. Oral replacement glucocorticoid therapy for adrenal insufficiency
d. Low-dose maintenance steroid therapy for other conditions (excluding steroid tapers for brain edema/metastases/radiation)
e. Steroid therapy for contrast reaction prophylaxis
f. Stable hormonal therapy for ovarian suppression for non-malignant conditions, hormonal contraceptive therapy , or post-menopausal hormone replacement therapy (HRT)*
g. GnRH analogs in patients with prostate cancer
h. Intra-articular steroid injections
i. Higher dose steroid therapy for treatment of an acute intercurrent illness in patients with stable disease or an ongoing response. In such situations, protocol therapy treatment should be interrupted.
*Prior or concomitant therapies are permitted; however, patients must have been on a stable dose for at least 6 months prior to study start, and if continuing must remain on the stable dose while receiving study treatment (i.e. such treatment will not be considered as systemic hormonal therapy for the purpose of study eligibility).
4. Use of hematopoietic growth factors within 2 weeks prior to C1/D1
5. Active second malignancy or history of another malignancy within the last 3 years, with the exception of:
a. Treated, non-melanoma skin cancers
b. Treated carcinoma in situ of the breast or cervix
c. Controlled, superficial carcinoma of the urinary bladder
d. T1a or b carcinoma of the prostate treated according to local standard of care, with prostate-specific antigen (PSA) within normal limits for the institution
6. Central nervous system (CNS) malignancy including:
a) Primary malignancies of the CNS
b) Known , untreated CNS or leptomeningeal metastases , or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS metastatic involvement for which treatment is required
Note: Patients with treated CNS metastases will be eligible if they are asymptomatic, do not require corticosteroids or anticonvulsants, and have confirmation of at least stable brain disease status as assessed by 2 imaging studies performed > 4 weeks apart with the most recent performed within 4 weeks prior to first trial drug administration
Patients with newly identified CNS metastases during study treatment will be considered to have PD and will be discontinued from treatment
7. Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy
Note: With the exception of persistent Grade 2 alopecia and/or peripheral neuropathy, patients must have recovered (to Grade ≤ 1) from acute toxicity by C1/D1
8. Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure
9. Non-healing wounds on any part of the body
10. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable
11. Active uncontrolled bleeding or a known bleeding diathesis
12. Significant cardiovascular disease or condition, including:
a. Congestive heart failure currently requiring therapy
b. Class III or IV cardiovascular disease according to the New York Heart Association's (NYHA) functional criteria
c. Need for antiarrhythmic medical therapy for a ventricular arrhythmia
d. Severe conduction disturbance (e.g. 3rd degree heart block)
e. Unstable angina pectoris (last episode at least 6 months prior to C1/D1)
f. Uncontrolled hypertension (per the Investigator's discretion)
g. Myocardial infarction within 6 months prior to C1/D1
13. Abnormal hematologic, renal or hepatic function as defined by the following criteria:
a. Absolute neutrophil count (ANC) <1.5 ×109/L (1500/mm3)
b. Hemoglobin ≤9 g/dL
c. Platelet count <75 ×109/L (75,000/mm3)
d. Serum creatinine >1.5 × upper limit of normal (ULN) for the institution
e. Aspartate aminotransferase (AST) >3.5 × ULN for the institution or AST >5 × ULN for the institution in case of known liver metastases
f. Alanine aminotransferase (ALT) >3.5 × ULN for the institution or ALT >5 × ULN for the institution in case of known liver metastases
g. Total bilirubin >1.5 × ULN for the institution
h. Prothrombin time as assessed by International Normalized Ratio (INR) >1.5 × ULN for the institution*
i. Partial thromboplastin time (PTT) >1.5 × ULN for the institution*
* unless the patient is on a stable dose of anticoagulant therapy for a prior thrombotic event
14. Any of the following within 2 weeks prior to C1/D1:
a. Any serious or uncontrolled infection
b. Any infection requiring parenteral antibiotics
c. Unexplained fever >38.0 °C
15. Known or suspected hypersensitivity to any of the excipients of the Sym015 drug product
16. Any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which in the opinion of the Investigator, would either compromise the patient’s safety or interfere with the evaluation of the safety of the trial drug
17. Any kind of disorder that compromises the ability of the patient to give written informed consent and/or to comply with trial procedures or is unwilling or unable to comply with trial requirements at the discretion of the Investigator
18. Breast feeding, or plans by the patient (or the patient’s partner) to become pregnant during treatment or within 4 months after the end of treatment
• Nitrosoureas and mitomycin C within 6 weeks prior to C1/D1
2. Part 2 ONLY:
a. Prior therapy with MET-inhibiting agents
Note: Exceptions will be a subset of approximately 6 patients entered to the Basket Cohort after having received prior therapy with a MET-targeting TKI, and patients entered to the NSCLC Cohort who may have received prior therapy with a METtargeting TKI.
b. Prior therapy with antibody to HGF
c. Basket Cohort ONLY: Tumor status demonstrating MET-polysomy in the absence of MET-amplification, as specified
Note: Patients in the NSCLC Cohort with polysomy are eligible
d. Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following the radiotherapy
Note: Radiotherapy for pain control against non-target lesions is allowed, as long as it does not influence bone marrow function
3. Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone equivalent) within 2 weeks prior to C1/D1 with the exception of the following allowed therapies:
a. Hormonal therapy (e.g. Megace) for appetite stimulation
b. Nasal, ophthalmic, inhaled, and topical glucocorticoid preparations
c. Oral replacement glucocorticoid therapy for adrenal insufficiency
d. Low-dose maintenance steroid therapy for other conditions (excluding steroid tapers for brain edema/metastases/radiation)
e. Steroid therapy for contrast reaction prophylaxis
f. Stable hormonal therapy for ovarian suppression for non-malignant conditions, hormonal contraceptive therapy , or post-menopausal hormone replacement therapy (HRT)*
g. GnRH analogs in patients with prostate cancer
h. Intra-articular steroid injections
i. Higher dose steroid therapy for treatment of an acute intercurrent illness in patients with stable disease or an ongoing response. In such situations, protocol therapy treatment should be interrupted.
*Prior or concomitant therapies are permitted; however, patients must have been on a stable dose for at least 6 months prior to study start, and if continuing must remain on the stable dose while receiving study treatment (i.e. such treatment will not be considered as systemic hormonal therapy for the purpose of study eligibility).
4. Use of hematopoietic growth factors within 2 weeks prior to C1/D1
5. Active second malignancy or history of another malignancy within the last 3 years, with the exception of:
a. Treated, non-melanoma skin cancers
b. Treated carcinoma in situ of the breast or cervix
c. Controlled, superficial carcinoma of the urinary bladder
d. T1a or b carcinoma of the prostate treated according to local standard of care, with prostate-specific antigen (PSA) within normal limits for the institution
6. Central nervous system (CNS) malignancy including:
a) Primary malignancies of the CNS
b) Known , untreated CNS or leptomeningeal metastases , or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS metastatic involvement for which treatment is required
Note: Patients with treated CNS metastases will be eligible if they are asymptomatic, do not require corticosteroids or anticonvulsants, and have confirmation of at least stable brain disease status as assessed by 2 imaging studies performed > 4 weeks apart with the most recent performed within 4 weeks prior to first trial drug administration
Patients with newly identified CNS metastases during study treatment will be considered to have PD and will be discontinued from treatment
7. Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy
Note: With the exception of persistent Grade 2 alopecia and/or peripheral neuropathy, patients must have recovered (to Grade ≤ 1) from acute toxicity by C1/D1
8. Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure
9. Non-healing wounds on any part of the body
10. Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 1 month prior to C1/D1, unless adequately treated and stable
11. Active uncontrolled bleeding or a known bleeding diathesis
12. Significant cardiovascular disease or condition, including:
a. Congestive heart failure currently requiring therapy
b. Class III or IV cardiovascular disease according to the New York Heart Association's (NYHA) functional criteria
c. Need for antiarrhythmic medical therapy for a ventricular arrhythmia
d. Severe conduction disturbance (e.g. 3rd degree heart block)
e. Unstable angina pectoris (last episode at least 6 months prior to C1/D1)
f. Uncontrolled hypertension (per the Investigator's discretion)
g. Myocardial infarction within 6 months prior to C1/D1
13. Abnormal hematologic, renal or hepatic function as defined by the following criteria:
a. Absolute neutrophil count (ANC) <1.5 ×109/L (1500/mm3)
b. Hemoglobin ≤9 g/dL
c. Platelet count <75 ×109/L (75,000/mm3)
d. Serum creatinine >1.5 × upper limit of normal (ULN) for the institution
e. Aspartate aminotransferase (AST) >3.5 × ULN for the institution or AST >5 × ULN for the institution in case of known liver metastases
f. Alanine aminotransferase (ALT) >3.5 × ULN for the institution or ALT >5 × ULN for the institution in case of known liver metastases
g. Total bilirubin >1.5 × ULN for the institution
h. Prothrombin time as assessed by International Normalized Ratio (INR) >1.5 × ULN for the institution*
i. Partial thromboplastin time (PTT) >1.5 × ULN for the institution*
* unless the patient is on a stable dose of anticoagulant therapy for a prior thrombotic event
14. Any of the following within 2 weeks prior to C1/D1:
a. Any serious or uncontrolled infection
b. Any infection requiring parenteral antibiotics
c. Unexplained fever >38.0 °C
15. Known or suspected hypersensitivity to any of the excipients of the Sym015 drug product
16. Any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which in the opinion of the Investigator, would either compromise the patient’s safety or interfere with the evaluation of the safety of the trial drug
17. Any kind of disorder that compromises the ability of the patient to give written informed consent and/or to comply with trial procedures or is unwilling or unable to comply with trial requirements at the discretion of the Investigator
18. Breast feeding, or plans by the patient (or the patient’s partner) to become pregnant during treatment or within 4 months after the end of treatment
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
72 participants
