Clinical Trials List
Protocol NumberCLAG525B2101
NCT Number(ClinicalTrials.gov Identfier)NCT03499899
2018-07-02 - 2021-06-08
Phase II
Terminated3
ICD-10C50
Malignant neoplasm of breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
A Phase II Open-label, Randomized, Three-arm, Multicenter Study of LAG525 Given in Combination With Spartalizumab (PDR001), or With Spartalizumab and Carboplatin, or With Carboplatin, as First or Second Line Therapy in Patients With Advanced Triple-negative Breast Cancer
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 金光亮 無
- Yi-Fang Tsai 無
- Ta-Chung Chao 無
- 邱仁輝 無
- 賴亦貞 無
- 林永慧 無
- Chun-Yu Liu 無
- 林燕淑 無
The Actual Total Number of Participants Enrolled
2 Completed
Audit
None
Co-Principal Investigator
- 陳怡君 無
- 羅喬 無
- 林季宏 無
- Ann-Lii Cheng 無
- 張端瑩 無
- Wei-Wu Chen 無
- MING-YANG WANG 無
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
Advanced Triple-negative Breast Cancer
Objectives
Primary objective(s)
To assess the antitumor activity of the three treatment arms LAG525 + spartalizumab, LAG525
+ spartalizumab + carboplatin and LAG525 + carboplatin, in subjects with advanced TNBC in
first or second line of therapy, as measured by the objective response rate (ORR) per
investigator’s assessment according to RECIST v1.1.
Secondary objective(s) Endpoint(s) for secondary objective(s)
To assess the efficacy of the three treatment arms with respect to Duration of response (DOR),
Time to response (TTR), Progression Free Survival (PFS) and Clinical benefit rate (CBR) per
investigator’s assessment according to RECIST v1.1
To assess Overall Survival for each treatment arm
To characterize the safety profile of each treatment arm
To characterize the pharmacokinetics (PK) of LAG525, spartalizumab, and carboplatin in the
three investigated combinations
To assess immunogenicity of LAG525 and spartalizumab in the three investigated combinations
Test Drug
LAG525、PDR001
Active Ingredient
LAG525
PDR001
PDR001
Dosage Form
Concentrate for solution for infusion
Concentrate for solution for infusion
Concentrate for solution for infusion
Dosage
100mg/2ml
100mg/4ml
100mg/4ml
Endpoints
Primary Outcome Measures :
Overall response rate (ORR) per RECIST v1.1 per investigators' assessment [ Time Frame: 24 months ]
To assess the antitumor activity of the three treatment arms LAG525 + spartalizumab, LAG525 + spartalizumab + carboplatin and LAG525 + carboplatin, in subjects with advanced TNBC in first or second line therapy, as measured by the overall response rate (ORR) per investigator's assessment according to RECIST v1.1.
Overall response rate (ORR) per RECIST v1.1 per investigators' assessment [ Time Frame: 24 months ]
To assess the antitumor activity of the three treatment arms LAG525 + spartalizumab, LAG525 + spartalizumab + carboplatin and LAG525 + carboplatin, in subjects with advanced TNBC in first or second line therapy, as measured by the overall response rate (ORR) per investigator's assessment according to RECIST v1.1.
Inclution Criteria
Inclusion criteria
Subjects eligible for inclusion in this study must meet all of the following criteria:
1. Patient is an adult ≥ 18 years old at the time of informed consent, and has signed informed
consent before any trial related activities and according to local guidelines
2. Patient has advanced (loco-regionally recurrent not amenable to curative therapy or
metastatic) breast cancer.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Patient has adequate bone marrow and organ function as defined by the following
laboratory values (as assessed by local laboratory for eligibility):
Absolute neutrophil count ≥ 1.5× 109/L
Platelets ≥ 100 × 109/L
Hemoglobin ≥ 9.0 g/dL
Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) ≥ 40
mL/min
Alanine aminotransferase (ALT) < 3 x ULN, except for patients that have tumor
involvement of the liver, who may only be included if ALT ≤5.0 x ULN who are
excluded if ALT > 5 x ULN
Aspartate aminotransferase (AST) < 3 x ULN, except for patients that have tumor
involvement of the liver, who may only be included if AST ≤5.0 x ULN who are
excluded if AST > 5 x ULN
Total serum bilirubin < 1.5 ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
within normal range of the central laboratory in patients with well documented
Gilbert’s Syndrome
5. Patient must have measurable disease, i.e., at least one measurable lesion as per RECIST
1.1 criteria (Tumor lesions previously irradiated or subjected to other loco-regional
therapy will only be considered measurable if disease progression at the treated site after
completion of therapy is clearly documented).
6. Patient progressed after adjuvant or 1 prior systemic treatment in the metastatic setting.
Patients with de novo metastatic disease are eligible if they received 1 prior line of
therapy.
7. Patient must have received prior systemic treatment that included taxane-based
chemotherapy for adjuvant or metastatic disease.
8. Patient must have a site of disease amenable to biopsy, and must be willing to undergo a
new tumor biopsy at screening and during therapy on this study, the latter if medically
feasible. Patients with an available archival tumor tissue do not need to perform a tumor
biopsy at screening if patient has not received anti-cancer therapy since the biopsy was
taken.
9. Patient has histologically and/or cytologically confirmed diagnosis of TNBC (based on
most recently analyzed biopsy, local lab) meeting the following criteria: HER2 negative in
situ hybridization test or an IHC status of 0 or 1+, and ER and PR expression is <1 percent
as determined by immunohistochemistry (IHC)
Subjects eligible for inclusion in this study must meet all of the following criteria:
1. Patient is an adult ≥ 18 years old at the time of informed consent, and has signed informed
consent before any trial related activities and according to local guidelines
2. Patient has advanced (loco-regionally recurrent not amenable to curative therapy or
metastatic) breast cancer.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Patient has adequate bone marrow and organ function as defined by the following
laboratory values (as assessed by local laboratory for eligibility):
Absolute neutrophil count ≥ 1.5× 109/L
Platelets ≥ 100 × 109/L
Hemoglobin ≥ 9.0 g/dL
Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) ≥ 40
mL/min
Alanine aminotransferase (ALT) < 3 x ULN, except for patients that have tumor
involvement of the liver, who may only be included if ALT ≤5.0 x ULN who are
excluded if ALT > 5 x ULN
Aspartate aminotransferase (AST) < 3 x ULN, except for patients that have tumor
involvement of the liver, who may only be included if AST ≤5.0 x ULN who are
excluded if AST > 5 x ULN
Total serum bilirubin < 1.5 ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
within normal range of the central laboratory in patients with well documented
Gilbert’s Syndrome
5. Patient must have measurable disease, i.e., at least one measurable lesion as per RECIST
1.1 criteria (Tumor lesions previously irradiated or subjected to other loco-regional
therapy will only be considered measurable if disease progression at the treated site after
completion of therapy is clearly documented).
6. Patient progressed after adjuvant or 1 prior systemic treatment in the metastatic setting.
Patients with de novo metastatic disease are eligible if they received 1 prior line of
therapy.
7. Patient must have received prior systemic treatment that included taxane-based
chemotherapy for adjuvant or metastatic disease.
8. Patient must have a site of disease amenable to biopsy, and must be willing to undergo a
new tumor biopsy at screening and during therapy on this study, the latter if medically
feasible. Patients with an available archival tumor tissue do not need to perform a tumor
biopsy at screening if patient has not received anti-cancer therapy since the biopsy was
taken.
9. Patient has histologically and/or cytologically confirmed diagnosis of TNBC (based on
most recently analyzed biopsy, local lab) meeting the following criteria: HER2 negative in
situ hybridization test or an IHC status of 0 or 1+, and ER and PR expression is <1 percent
as determined by immunohistochemistry (IHC)
Exclusion Criteria
Exclusion criteria
Subjects meeting any of the following criteria are not eligible for inclusion in this study.
1. Patient has received prior treatment with anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PDL2 antibody (any line of therapy).
2. Patient received prior therapy with a platinum agent or mitomycin and experienced
recurrence within 12 months after the end of the platinum-based or mitomycin containing
therapy.
3. Patient is concurrently using other anti-cancer therapy.
4. Patient has had major surgery within 14 days prior to starting study treatment or has not
recovered to grade 1 or less from major side effects.
5. Patient with presence of CTCAE ≥ grade 2 toxicity (except alopecia, peripheral
neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer
therapy.
6. Patient has received radiotherapy ≤ 4 weeks prior to randomization (≤ 2 weeks for limited
field radiation for palliation), and has not recovered to grade 1 or better from related side
effects of such therapy (with the exception of alopecia).
7. Patient has a known hypersensitivity to other monoclonal antibodies, platinum-containing
compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin.
8. Patient with history of Stevens-Johnson syndrome or Toxic epidermal necrolysis, or a
history of severe hypersensitivity reactions, which in the opinion of the investigator may
pose an increased risk of serious infusion reaction.
9. History of acute pancreatitis within 1 year of screening or past medical history of chronic
pancreatitis.
10. Clinically significant cardiac disease or impaired cardiac function, including any of the
following: Cardiac or cardiac repolarization abnormality, including any of the following:
1. History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft
(CABG) within 6 months prior to starting study treatment
2. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left
bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and
third degree AV block) or uncontrolled hypertension
3. QTcF > 470 msec on screening central ECG or long QT syndrome, family history of
idiopathic sudden death or congenital long QT syndrome, or any of the following:
Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or
hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia
Concomitant medication(s) known to cause Torsades de Pointe” per www.qtdrugs.org
that cannot be discontinued or replaced by safe alternative medication. (within 5 halflives or 7 days prior to starting study drug)
Inability to determine the QTcF interval
11. Patient has active, known or suspected autoimmune disease or immune deficiency.
Patients with vitiligo, type I diabetes on stable insulin, residual hypothyroidism only
requiring hormone replacement, psoriasis not requiring systemic treatment or conditions
not expected to recur in the absence of an external trigger should not be excluded.
12. History of allogenic bone marrow or solid organ transplant.
13. History of or current interstitial lung disease or pneumonitis, including clinically
significant radiation pneumonitis (i.e., affecting activities of daily living or requiring
therapeutic intervention).
14. Patient has a concurrent malignancy or malignancy within 3 years of randomization, with
the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous
skin cancer or curatively resected carcinoma in situ of any type.
15. Patient with history or presence of central nervous system (CNS) metastases, treated or
untreated.
16. Patient has carcinomatous meningitis
17. Patient has clinically significant active bleeding or history thereof within four weeks prior
to randomization.
18. Patient has active infection requiring systemic antibiotic therapy. Patients requiring
systemic antibiotics for infection must have completed therapy before screening is
initiated.
Patient has a known history of HIV infection (testing not mandatory).
Patients with active Hepatitis B infection (HBsAg positive) or hepatitis C infection.
Note: Patients with antecedent of Hepatitis B (anti-HBc positive, HBsAg and HBV-DNA
negative) are eligible.
Patients with positive test for hepatitis C ribonucleic acid (HCV RNA).
Note: Patients in whom HCV infection resolved spontaneously (positive HCV antibodies
without detectable HCV-RNA) or those that achieved a sustained virological response
after antiviral treatment and show absence of detectable HCV RNA ≥ 6 months (with the
use of IFN-free regimes) or ≥ 12 months (with the use of IFN-based regimes) after
cessation of antiviral treatment are eligible.
19. Patient received any live vaccine against infectious disease (e.g., varicella, pneumococcus,
yellow fever vaccine) within 4 weeks of initiation of study treatment
20. Patient is currently receiving or has received systemic corticosteroids or any
immunosuppressive therapy (≥ 10mg/day prednisone or equivalent) within 7 days prior to
starting study drug (other than replacement-dose steroids in the setting of adrenal
insufficiency), or who have not fully recovered from side effects of such treatment.
Topical, inhaled, nasal and ophthalmic steroids are allowed.
21. Patient has any medical condition that would, in the investigator’s judgment, prevent the
patient’s participation in the clinical study due to safety concerns, compliance with clinical
study procedures or interpretation of study results
22. Participation in an interventional, investigational study within 2 weeks prior to the first
dose of study treatment
23. Women of child-bearing potential defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during study treatment and for 6 months after the last any dose of study treatment. Highly
effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking
study treatment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the
study the vasectomized male partner should be the sole partner for that patient
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e., age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least
six weeks ago. In the case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment is she considered
not of child bearing potential.
24. Sexually active males unwilling to use a condom during intercourse while taking study
treatment, and up for 6 months after stopping study treatment. A condom is required for
all sexually active male participants to prevent them from fathering a child AND to
prevent delivery of study treatment via seminal fluid to their partner. In addition, male
participants must not donate sperm for the time period specified above.
No additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible subjects
Subjects meeting any of the following criteria are not eligible for inclusion in this study.
1. Patient has received prior treatment with anti-LAG-3, anti-PD-1, anti-PD-L1, or anti-PDL2 antibody (any line of therapy).
2. Patient received prior therapy with a platinum agent or mitomycin and experienced
recurrence within 12 months after the end of the platinum-based or mitomycin containing
therapy.
3. Patient is concurrently using other anti-cancer therapy.
4. Patient has had major surgery within 14 days prior to starting study treatment or has not
recovered to grade 1 or less from major side effects.
5. Patient with presence of CTCAE ≥ grade 2 toxicity (except alopecia, peripheral
neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer
therapy.
6. Patient has received radiotherapy ≤ 4 weeks prior to randomization (≤ 2 weeks for limited
field radiation for palliation), and has not recovered to grade 1 or better from related side
effects of such therapy (with the exception of alopecia).
7. Patient has a known hypersensitivity to other monoclonal antibodies, platinum-containing
compounds, or to any of the excipients of LAG525, spartalizumab, or carboplatin.
8. Patient with history of Stevens-Johnson syndrome or Toxic epidermal necrolysis, or a
history of severe hypersensitivity reactions, which in the opinion of the investigator may
pose an increased risk of serious infusion reaction.
9. History of acute pancreatitis within 1 year of screening or past medical history of chronic
pancreatitis.
10. Clinically significant cardiac disease or impaired cardiac function, including any of the
following: Cardiac or cardiac repolarization abnormality, including any of the following:
1. History of myocardial infarction (MI), angina pectoris, coronary artery bypass graft
(CABG) within 6 months prior to starting study treatment
2. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left
bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and
third degree AV block) or uncontrolled hypertension
3. QTcF > 470 msec on screening central ECG or long QT syndrome, family history of
idiopathic sudden death or congenital long QT syndrome, or any of the following:
Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or
hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia
Concomitant medication(s) known to cause Torsades de Pointe” per www.qtdrugs.org
that cannot be discontinued or replaced by safe alternative medication. (within 5 halflives or 7 days prior to starting study drug)
Inability to determine the QTcF interval
11. Patient has active, known or suspected autoimmune disease or immune deficiency.
Patients with vitiligo, type I diabetes on stable insulin, residual hypothyroidism only
requiring hormone replacement, psoriasis not requiring systemic treatment or conditions
not expected to recur in the absence of an external trigger should not be excluded.
12. History of allogenic bone marrow or solid organ transplant.
13. History of or current interstitial lung disease or pneumonitis, including clinically
significant radiation pneumonitis (i.e., affecting activities of daily living or requiring
therapeutic intervention).
14. Patient has a concurrent malignancy or malignancy within 3 years of randomization, with
the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous
skin cancer or curatively resected carcinoma in situ of any type.
15. Patient with history or presence of central nervous system (CNS) metastases, treated or
untreated.
16. Patient has carcinomatous meningitis
17. Patient has clinically significant active bleeding or history thereof within four weeks prior
to randomization.
18. Patient has active infection requiring systemic antibiotic therapy. Patients requiring
systemic antibiotics for infection must have completed therapy before screening is
initiated.
Patient has a known history of HIV infection (testing not mandatory).
Patients with active Hepatitis B infection (HBsAg positive) or hepatitis C infection.
Note: Patients with antecedent of Hepatitis B (anti-HBc positive, HBsAg and HBV-DNA
negative) are eligible.
Patients with positive test for hepatitis C ribonucleic acid (HCV RNA).
Note: Patients in whom HCV infection resolved spontaneously (positive HCV antibodies
without detectable HCV-RNA) or those that achieved a sustained virological response
after antiviral treatment and show absence of detectable HCV RNA ≥ 6 months (with the
use of IFN-free regimes) or ≥ 12 months (with the use of IFN-based regimes) after
cessation of antiviral treatment are eligible.
19. Patient received any live vaccine against infectious disease (e.g., varicella, pneumococcus,
yellow fever vaccine) within 4 weeks of initiation of study treatment
20. Patient is currently receiving or has received systemic corticosteroids or any
immunosuppressive therapy (≥ 10mg/day prednisone or equivalent) within 7 days prior to
starting study drug (other than replacement-dose steroids in the setting of adrenal
insufficiency), or who have not fully recovered from side effects of such treatment.
Topical, inhaled, nasal and ophthalmic steroids are allowed.
21. Patient has any medical condition that would, in the investigator’s judgment, prevent the
patient’s participation in the clinical study due to safety concerns, compliance with clinical
study procedures or interpretation of study results
22. Participation in an interventional, investigational study within 2 weeks prior to the first
dose of study treatment
23. Women of child-bearing potential defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during study treatment and for 6 months after the last any dose of study treatment. Highly
effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking
study treatment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the
study the vasectomized male partner should be the sole partner for that patient
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e., age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least
six weeks ago. In the case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment is she considered
not of child bearing potential.
24. Sexually active males unwilling to use a condom during intercourse while taking study
treatment, and up for 6 months after stopping study treatment. A condom is required for
all sexually active male participants to prevent them from fathering a child AND to
prevent delivery of study treatment via seminal fluid to their partner. In addition, male
participants must not donate sperm for the time period specified above.
No additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible subjects
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
84 participants
