Clinical Trials List
Protocol NumberCA025-006
NCT Number(ClinicalTrials.gov Identfier)NCT03336216
2018-10-01 - 2021-08-31
Phase II
Terminated2
ICD-10C25
Malignant neoplasm of pancreas
A Phase 2 Study of Cabiralizumab (BMS-986227, FPA008) Administered in Combination With Nivolumab (BMS-936558) With and Without Chemotherapy in Patients With Advanced Pancreatic Cancer
-
Trial Applicant
BRISTOL-MYERS SQUIBB (TAIWAN) LTD.
-
Sponsor
Bristol-Myers Squibb
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yi-Ping Hung Division of Hematology & Oncology
- Ming-Huang Chen Division of Hematology & Oncology
- Yun-Cheng Hsieh Digestive System Department
- Yee Chao Division of Hematology & Oncology
- Pei-Chang Lee Digestive System Department
The Actual Total Number of Participants Enrolled
6 Terminated
Audit
CRO
Co-Principal Investigator
- Ann-Lii Cheng Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- 陳國興 Division of Hematology & Oncology
- SHIH-HUNG YANG Division of Hematology & Oncology
- TA-CHEN HUANG Division of Hematology & Oncology
- Hsiang-Fong Kao Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- 梁逸歆 Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
- SHIH-HUNG YANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Advanced Pancreatic Cancer
Objectives
Primary
To evaluate the PFS of cabiralizumab administered in combination
with nivolumab with and without chemotherapy relative to
investigator’s choice of chemotherapy in participants with
advanced/metastatic pancreatic cancer who progressed on or after the
first line of chemotherapy (either gemcitabine-based or 5-fluorouracil
(5-FU)-based chemotherapy).
Secondary
To assess the safety of cabiralizumab administered in combination with
nivolumab with and without chemotherapy in participants with
advanced/metastatic pancreatic cancer who progressed on or after the
first line of chemotherapy (either gemcitabine-based or 5-FU-based
chemotherapy).
To characterize the pharmacokinetics (PK) of cabiralizumab
administered in combination with nivolumab with and without
chemotherapy
To evaluate the anti-tumor activity of cabiralizumab administered in
combination with nivolumab with and without chemotherapy relative
to investigator’s choice of chemotherapy in participants with
advanced/metastatic pancreatic cancer who progressed on or after the
first line of chemotherapy (either gemcitabine-based or 5-FU-based
chemotherapy) using RECIST v1.1.
To assess overall survival rate (OSR).
Test Drug
Cabiralizumab (BMS-986227, FPA008)
Active Ingredient
Cabiralizumab
Dosage Form
injection
Dosage
100 mg/ 5ml
Endpoints
Primary
Median progression-free survival (mPFS) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Secondary
Incidence of adverse events(AEs), serious adverse events(SAEs), AEs leading to discontinuation, death, and laboratory abnormalities
Summary measures of PK parameters of cabiralizumab and nivolumab
Objective Response Rate (ORR), median duration of response (mDOR), and progression-free survival rate
(PFSR) at 6, 9, and 12 months by RECIST v1.1
OSR at 6 months, 1 year, and 2 years
Median progression-free survival (mPFS) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Secondary
Incidence of adverse events(AEs), serious adverse events(SAEs), AEs leading to discontinuation, death, and laboratory abnormalities
Summary measures of PK parameters of cabiralizumab and nivolumab
Objective Response Rate (ORR), median duration of response (mDOR), and progression-free survival rate
(PFSR) at 6, 9, and 12 months by RECIST v1.1
OSR at 6 months, 1 year, and 2 years
Inclution Criteria
Inclusion Criteria
1) Signed Written Informed Consent
a) Participants must have signed and dated an Institutional Review Board
(IRB)/Independent Ethics Committee (IEC) approved written informed consent form in
accordance with regulatory and institutional guidelines. This must be obtained before the
performance of any protocol related procedures that are not part of normal participant
care.
b) Consent for fresh pre-treatment, on-treatment, and upon progression biopsy samples at
acceptable clinical risk, as judged by the investigator.
c) Participants must be willing and able to comply with scheduled visits, treatment schedule,
and laboratory testing.
2) Type of Participant and Target Disease Characteristics
a) Participants must be at least 18 years old.
b) Participants must have histological or cytological confirmed diagnosis of locally
advanced or metastatic adenocarcinoma of the pancreas, which has progressed during or
after no more than one line of systemic chemotherapy in the metastatic setting
(gemcitabine or 5-fluoruracil-based regimens).
i) If a participant received adjuvant/neoadjuvant systemic therapy, and progressed
within 6 months, the adjuvant/neoadjuvant treatment will be considered as one line of
systemic treatment.
c) In general, discontinuation of one drug in a multi-drug regimen and continuation of other
drug(s), is considered part of the same line of treatment. Restarting the same regimen
after a drug holiday or maintenance chemotherapy can also be considered part of the
same line of treatment. Switching from IV (5-FU) to an oral formulation (capecitabine) of
the same drug is also considered part of the same line of treatment.
d) Minimum time from first systemic therapy for recurrent/metastatic adenocarcinoma of
pancreas to progression should be at least 3 months
3) General Inclusion Criteria
a) Participants must have measurable disease by RECIST v1.1 (Appendix 5) and have at
least 1 lesion accessible for biopsy in addition to the target lesion.
i) Participants with lesions in a previously irradiated field as the sole site of measurable
disease will be permitted to enroll provided the lesion(s) have demonstrated clear
progression and can be measured.
b) Prior palliative radiotherapy must have been completed at least 2 weeks prior to the first
dose of the study treatment. Participants with symptomatic tumor lesions at baseline that
may require palliative radiotherapy within 4 weeks of the first dose of study treatment are
strongly encouraged to receive palliative radiotherapy prior to enrollment.
c) Eastern Cooperative Oncology Group (ECOG) performance status of 1
d) All participants will be required to undergo mandatory pre- and on-treatment biopsies.
i) An archival sample is acceptable only if there is no systemic therapy administered
after the archival sample is collected.
ii) Participants whose pretreatment biopsy yields inadequate tissue quantity or quality
that do not have an appropriate archival sample will not be eligible (exception: Up to
approximately 8 participants/cohort (20%) will be allowed on treatment with a pretreatment
biopsy that does not yield adequate tissue quantity/quality).
iii) If a participant had a biopsy in the preceding 90 days with no intervening anti-cancer
therapy, participants can be enrolled without needing a repeat biopsy after discussion
with the BMS Medical Monitor and availability of FFPE blocks or unstained slides as
delineated below. Participants will however be required to undergo on-treatment and
upon progression biopsies at acceptable clinical risk as judged by the investigator in
all arms.
iv) Pretreatment tumor tissue will be assessed for adequate tumor content prior to
participants receiving study treatment. Pretreatment tissue must be collected and
confirmed for adequate tissue quantity (20 slides) and quality (100 viable tumor cells
and 20% tumor content) during the screening period prior to first dose of study
treatment. Participants who had a biopsy after signing consent which confirmed
diagnosis but did not yield sufficient tissue for all correlative studies may be allowed
after discussion with the BMS Medical Monitor.
v) The tumor tissue specimen must be a core needle biopsy, excisional or incisional
biopsy. Fine needle biopsies, drainage of pleural effusions with cytospins, or punch
biopsies are not considered adequate for biomarker review.
vi) Where possible, the biopsied lesion should be distinct from target lesions being
evaluated for radiologic response, and the same lesion should be used for both the
baseline and on-treatment sampling.
e) Adequate marrow function as defined by the following:
i) White blood cell (WBC) 2000/L (stable off any growth factor within 4 weeks of
first study treatment administration);
ii) Neutrophils 1500/L (stable off any growth factor within 4 weeks of first study
treatment administration);
iii) Platelets 100 103/L (transfusion to achieve this level is not permitted within
2 weeks of first study treatment administration);
iv) Hemoglobin 8.5 g/dL (transfusion to achieve this level is not permitted within
2 weeks of first study treatment administration).
f) Adequate other organ functions as defined by the following:
i) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
2 institutional ULN
ii) Total bilirubin 1.5 x institutional ULN (except participants with Gilbert’s Syndrome
who must have normal direct bilirubin)
iii) Serum creatinine 1.5 x ULN or creatinine clearance (CLcr) 40 mL/min (measured
using the Cockcroft-Gault formula below):
Female CLcr =
(140 − age in years) × weight in kg × 0.85
72 × serum creatinine in mg/dL
Male CLcr =
(140 − age in years) × weight in kg × 1.00
72 × serum creatinine in mg/dL
g) Ability to comply with study visits, treatment, procedures, PK and PD sample collection,
and required study follow-up.
4) Age and Reproductive Status
a) Males and females, ages 18 or age of majority or older.
b) Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24
hours prior to the start of study treatment.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration
of treatment with study treatment(s) and for a total of 5 months posttreatment completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception (Appendix 4) for the duration of treatment with study
treatment(s) and for a total of 7 months posttreatment completion. In addition, male
participants must be willing to refrain from sperm donation during this time.
f) Azoospermic males are exempt from contraceptive requirements. WOCBP who are
continuously not heterosexually active are also exempt from contraceptive requirements,
but still must undergo pregnancy testing as described in this section.
1) Signed Written Informed Consent
a) Participants must have signed and dated an Institutional Review Board
(IRB)/Independent Ethics Committee (IEC) approved written informed consent form in
accordance with regulatory and institutional guidelines. This must be obtained before the
performance of any protocol related procedures that are not part of normal participant
care.
b) Consent for fresh pre-treatment, on-treatment, and upon progression biopsy samples at
acceptable clinical risk, as judged by the investigator.
c) Participants must be willing and able to comply with scheduled visits, treatment schedule,
and laboratory testing.
2) Type of Participant and Target Disease Characteristics
a) Participants must be at least 18 years old.
b) Participants must have histological or cytological confirmed diagnosis of locally
advanced or metastatic adenocarcinoma of the pancreas, which has progressed during or
after no more than one line of systemic chemotherapy in the metastatic setting
(gemcitabine or 5-fluoruracil-based regimens).
i) If a participant received adjuvant/neoadjuvant systemic therapy, and progressed
within 6 months, the adjuvant/neoadjuvant treatment will be considered as one line of
systemic treatment.
c) In general, discontinuation of one drug in a multi-drug regimen and continuation of other
drug(s), is considered part of the same line of treatment. Restarting the same regimen
after a drug holiday or maintenance chemotherapy can also be considered part of the
same line of treatment. Switching from IV (5-FU) to an oral formulation (capecitabine) of
the same drug is also considered part of the same line of treatment.
d) Minimum time from first systemic therapy for recurrent/metastatic adenocarcinoma of
pancreas to progression should be at least 3 months
3) General Inclusion Criteria
a) Participants must have measurable disease by RECIST v1.1 (Appendix 5) and have at
least 1 lesion accessible for biopsy in addition to the target lesion.
i) Participants with lesions in a previously irradiated field as the sole site of measurable
disease will be permitted to enroll provided the lesion(s) have demonstrated clear
progression and can be measured.
b) Prior palliative radiotherapy must have been completed at least 2 weeks prior to the first
dose of the study treatment. Participants with symptomatic tumor lesions at baseline that
may require palliative radiotherapy within 4 weeks of the first dose of study treatment are
strongly encouraged to receive palliative radiotherapy prior to enrollment.
c) Eastern Cooperative Oncology Group (ECOG) performance status of 1
d) All participants will be required to undergo mandatory pre- and on-treatment biopsies.
i) An archival sample is acceptable only if there is no systemic therapy administered
after the archival sample is collected.
ii) Participants whose pretreatment biopsy yields inadequate tissue quantity or quality
that do not have an appropriate archival sample will not be eligible (exception: Up to
approximately 8 participants/cohort (20%) will be allowed on treatment with a pretreatment
biopsy that does not yield adequate tissue quantity/quality).
iii) If a participant had a biopsy in the preceding 90 days with no intervening anti-cancer
therapy, participants can be enrolled without needing a repeat biopsy after discussion
with the BMS Medical Monitor and availability of FFPE blocks or unstained slides as
delineated below. Participants will however be required to undergo on-treatment and
upon progression biopsies at acceptable clinical risk as judged by the investigator in
all arms.
iv) Pretreatment tumor tissue will be assessed for adequate tumor content prior to
participants receiving study treatment. Pretreatment tissue must be collected and
confirmed for adequate tissue quantity (20 slides) and quality (100 viable tumor cells
and 20% tumor content) during the screening period prior to first dose of study
treatment. Participants who had a biopsy after signing consent which confirmed
diagnosis but did not yield sufficient tissue for all correlative studies may be allowed
after discussion with the BMS Medical Monitor.
v) The tumor tissue specimen must be a core needle biopsy, excisional or incisional
biopsy. Fine needle biopsies, drainage of pleural effusions with cytospins, or punch
biopsies are not considered adequate for biomarker review.
vi) Where possible, the biopsied lesion should be distinct from target lesions being
evaluated for radiologic response, and the same lesion should be used for both the
baseline and on-treatment sampling.
e) Adequate marrow function as defined by the following:
i) White blood cell (WBC) 2000/L (stable off any growth factor within 4 weeks of
first study treatment administration);
ii) Neutrophils 1500/L (stable off any growth factor within 4 weeks of first study
treatment administration);
iii) Platelets 100 103/L (transfusion to achieve this level is not permitted within
2 weeks of first study treatment administration);
iv) Hemoglobin 8.5 g/dL (transfusion to achieve this level is not permitted within
2 weeks of first study treatment administration).
f) Adequate other organ functions as defined by the following:
i) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
2 institutional ULN
ii) Total bilirubin 1.5 x institutional ULN (except participants with Gilbert’s Syndrome
who must have normal direct bilirubin)
iii) Serum creatinine 1.5 x ULN or creatinine clearance (CLcr) 40 mL/min (measured
using the Cockcroft-Gault formula below):
Female CLcr =
(140 − age in years) × weight in kg × 0.85
72 × serum creatinine in mg/dL
Male CLcr =
(140 − age in years) × weight in kg × 1.00
72 × serum creatinine in mg/dL
g) Ability to comply with study visits, treatment, procedures, PK and PD sample collection,
and required study follow-up.
4) Age and Reproductive Status
a) Males and females, ages 18 or age of majority or older.
b) Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24
hours prior to the start of study treatment.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration
of treatment with study treatment(s) and for a total of 5 months posttreatment completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception (Appendix 4) for the duration of treatment with study
treatment(s) and for a total of 7 months posttreatment completion. In addition, male
participants must be willing to refrain from sperm donation during this time.
f) Azoospermic males are exempt from contraceptive requirements. WOCBP who are
continuously not heterosexually active are also exempt from contraceptive requirements,
but still must undergo pregnancy testing as described in this section.
Exclusion Criteria
Exclusion Criteria
1) Target Disease Exclusions
a) Suspected or known CNS metastases (imaging required only if participants are
symptomatic).
2) Medical History and Concurrent Disease
a) Participants with active, known, or suspected autoimmune disease. Participants with
vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition
only requiring hormone replacement, euthyroid participants with a history of Grave’s
disease (participants with suspected autoimmune thyroid disorders must be negative for
thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin
prior to first dose of study treatment), psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted to
enroll after discussing with the BMS Medical Monitor.
b) Participants with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone equivalents) or other immunosuppressive medications within
14 days of study treatment administration except for adrenal replacement steroid doses
> 10 mg daily prednisone equivalent in the absence of active autoimmune disease.
Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating
study treatment is permitted.
c) Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected treatment-related pulmonary toxicity.
d) Current or history of clinically significant muscle disorders (eg, myositis), recent
unresolved muscle injury, or any condition known to elevate serum CK levels.
e) Uncontrolled or significant cardiovascular disease including, but not limited to, any of the
following:
i) Myocardial infarction or stroke/transient ischemic attack within the past 6 months
ii) Uncontrolled angina within the past 3 months
iii) Any history of clinically significant arrhythmias (such as ventricular tachycardia,
ventricular fibrillation, or torsades de pointes)
iv) History of other clinically significant heart disease (eg, cardiomyopathy, congestive
heart failure with New York Heart Association functional classification III to IV,
pericarditis, significant pericardial effusion, or myocarditis)
v) Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
f) History of any chronic hepatitis as evidenced by the following:
i) Positive test for hepatitis B surface antigen
ii) Positive test for qualitative hepatitis C viral load (by polymerase chain reaction
[PCR]).
Note: Participants with positive hepatitis C antibody and negative quantitative hepatitis
C by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion
criterion.
g) Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric,
colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless complete
remission was achieved at least 2 years prior to study entry and no additional therapy is
required during the study period.
h) Prior organ allograft or allogeneic bone marrow transplantation.
i) Any major surgery within 4 weeks of study treatment. Participants must have recovered
from the effects of major surgery or significant traumatic injury at least 14 days before
the first dose of study treatment.
j) All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must
have resolved to Grade 1 (National Cancer Institute Common Terminology Criteria for
Adverse Events [NCI CTCAE] v4.03) or baseline before administration of study
treatment. Participants with toxicities attributed to prior anti-cancer therapy that are not
expected to resolve and result in long lasting sequelae, such as neuropathy after platinumbased
therapy, are permitted to enroll.
k) Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or
anti-fungal therapy 7 days prior to administration of study medication.
l) Any uncontrolled inflammatory GI disease including Crohn’s Disease and ulcerative
colitis.
m) Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (Testing for HIV must be performed at sites
mandated by local requirements.)
n) Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the
Investigator, would pose a risk to participant safety or interfere with study participation
or interpretation of individual participant results.
o) Not Applicable as per Revised Protocol 02 - Current or recent (within 3 months of study
drug administration) gastrointestinal disease that could impact upon the absorption of
study drug.
p) Transfusion completed within 72 hours prior to first dose of study drug administration
q) Not Applicable as per Revised Protocol 01 - Any GI surgery that could impact upon the
absorption of study drug.
r) Not Applicable as per Revised Protocol 01 - Inability to tolerate oral medication.
s) Inability to be venipunctured and/or tolerate venous access.
t) Positive test for latent tuberculosis (TB) at screening (eg, T-SPOT or Quantiferon test) or
evidence of active TB.
3) Prior Therapies
a) Prior exposure to anti-CSF1R, anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4.
b) Any anti-cancer therapy (eg, chemotherapy, biologics, vaccines, or hormonal treatment)
including investigational drugs within 4 weeks prior to the first dose of study treatment
administration, except for non-cytotoxic therapies, for which at least 4 weeks or 5 halflives
(whichever is shorter) must have elapsed between last dose and first treatment with
any study treatments; if 5 half-lives are shorter than 4 weeks, agreement with the Medical
Monitor must be obtained.
c) Treatment with botanical preparations (eg, herbal supplements, including potential drugs
of abuse, or traditional Chinese medicines) intended for general health support or to treat
the disease under study within 2 weeks prior to randomization/treatment.
d) Prior exposure to gemcitabine and 5-FU or gemcitabine and oxaliplatin co-administered
as first line treatment.
4) Restricted Concomitant Therapies
a) Concomitant use of statins while on study. However, a participant using statins for over
3 months prior to study drug administration and in stable status without CK rise may be
permitted to enroll.
b) Non-oncology vaccine therapies for prevention of infectious diseases (eg, human
papillomay virus vaccine) within 4 weeks of study drug administration. The inactivated
seasonal influenza vaccine can be given to participants before treatment and while on
therapy without restriction. Influenza vaccines containing live virus or other clinically
indicated vaccinations for infectious diseases (ie, pneumovax, varicella, etc) may be
permitted, but must be discussed with the BMS Medical Monitor and may require a study
drug washout period prior to and after administration of vaccine.
5) Physical and Laboratories Test Findings
a) Participants with abnormal serum chemistry values, which in the opinion of the
investigator is considered to be clinically significant, will be excluded from the study.
This will include participants who show clinical signs and symptoms related to their
abnormal serum chemistry values, as well as participants whose serum chemistry values
are asymptomatic but clinically significant (eg, hypokalemia or hyponatremia).
b) Evidence of coagulopathy or bleeding diathesis
c) Ascites needing paracentesis or medical management
d) Peripheral Neuropathy greater than Grade 1
e) Albumin less than 3 g/dL
f) Evidence of organ dysfunction or any clinically significant deviation from normal in
physical examination, vital signs, ECG, or clinical laboratory determinations beyond
what is consistent with the target population
6) Allergies and Adverse Drug Reactions
a) Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and
Tween 80 (polysorbate 80)
b) History of allergy to study treatments or any of its components of the study arm that
participant is enrolling
7) Other Exclusion Criteria
a) Not applicable per Revised Protocol 02 - Consumption of non-pasteurized milk while on
study drug and for 30 days after discontinuing study drug
b) Pregnant or breastfeeding
c) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific
circumstances a person who has been imprisoned may be included or permitted to
continue as a participant. Strict conditions apply and BMS approval is required.
d) Participants who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness
1) Target Disease Exclusions
a) Suspected or known CNS metastases (imaging required only if participants are
symptomatic).
2) Medical History and Concurrent Disease
a) Participants with active, known, or suspected autoimmune disease. Participants with
vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition
only requiring hormone replacement, euthyroid participants with a history of Grave’s
disease (participants with suspected autoimmune thyroid disorders must be negative for
thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin
prior to first dose of study treatment), psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted to
enroll after discussing with the BMS Medical Monitor.
b) Participants with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone equivalents) or other immunosuppressive medications within
14 days of study treatment administration except for adrenal replacement steroid doses
> 10 mg daily prednisone equivalent in the absence of active autoimmune disease.
Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating
study treatment is permitted.
c) Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected treatment-related pulmonary toxicity.
d) Current or history of clinically significant muscle disorders (eg, myositis), recent
unresolved muscle injury, or any condition known to elevate serum CK levels.
e) Uncontrolled or significant cardiovascular disease including, but not limited to, any of the
following:
i) Myocardial infarction or stroke/transient ischemic attack within the past 6 months
ii) Uncontrolled angina within the past 3 months
iii) Any history of clinically significant arrhythmias (such as ventricular tachycardia,
ventricular fibrillation, or torsades de pointes)
iv) History of other clinically significant heart disease (eg, cardiomyopathy, congestive
heart failure with New York Heart Association functional classification III to IV,
pericarditis, significant pericardial effusion, or myocarditis)
v) Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
f) History of any chronic hepatitis as evidenced by the following:
i) Positive test for hepatitis B surface antigen
ii) Positive test for qualitative hepatitis C viral load (by polymerase chain reaction
[PCR]).
Note: Participants with positive hepatitis C antibody and negative quantitative hepatitis
C by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion
criterion.
g) Previous malignancies (except non-melanoma skin cancers, and in situ bladder, gastric,
colorectal, endometrial, cervical/dysplasia, melanoma, or breast cancers) unless complete
remission was achieved at least 2 years prior to study entry and no additional therapy is
required during the study period.
h) Prior organ allograft or allogeneic bone marrow transplantation.
i) Any major surgery within 4 weeks of study treatment. Participants must have recovered
from the effects of major surgery or significant traumatic injury at least 14 days before
the first dose of study treatment.
j) All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must
have resolved to Grade 1 (National Cancer Institute Common Terminology Criteria for
Adverse Events [NCI CTCAE] v4.03) or baseline before administration of study
treatment. Participants with toxicities attributed to prior anti-cancer therapy that are not
expected to resolve and result in long lasting sequelae, such as neuropathy after platinumbased
therapy, are permitted to enroll.
k) Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, anti-viral or
anti-fungal therapy 7 days prior to administration of study medication.
l) Any uncontrolled inflammatory GI disease including Crohn’s Disease and ulcerative
colitis.
m) Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (Testing for HIV must be performed at sites
mandated by local requirements.)
n) Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the
Investigator, would pose a risk to participant safety or interfere with study participation
or interpretation of individual participant results.
o) Not Applicable as per Revised Protocol 02 - Current or recent (within 3 months of study
drug administration) gastrointestinal disease that could impact upon the absorption of
study drug.
p) Transfusion completed within 72 hours prior to first dose of study drug administration
q) Not Applicable as per Revised Protocol 01 - Any GI surgery that could impact upon the
absorption of study drug.
r) Not Applicable as per Revised Protocol 01 - Inability to tolerate oral medication.
s) Inability to be venipunctured and/or tolerate venous access.
t) Positive test for latent tuberculosis (TB) at screening (eg, T-SPOT or Quantiferon test) or
evidence of active TB.
3) Prior Therapies
a) Prior exposure to anti-CSF1R, anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4.
b) Any anti-cancer therapy (eg, chemotherapy, biologics, vaccines, or hormonal treatment)
including investigational drugs within 4 weeks prior to the first dose of study treatment
administration, except for non-cytotoxic therapies, for which at least 4 weeks or 5 halflives
(whichever is shorter) must have elapsed between last dose and first treatment with
any study treatments; if 5 half-lives are shorter than 4 weeks, agreement with the Medical
Monitor must be obtained.
c) Treatment with botanical preparations (eg, herbal supplements, including potential drugs
of abuse, or traditional Chinese medicines) intended for general health support or to treat
the disease under study within 2 weeks prior to randomization/treatment.
d) Prior exposure to gemcitabine and 5-FU or gemcitabine and oxaliplatin co-administered
as first line treatment.
4) Restricted Concomitant Therapies
a) Concomitant use of statins while on study. However, a participant using statins for over
3 months prior to study drug administration and in stable status without CK rise may be
permitted to enroll.
b) Non-oncology vaccine therapies for prevention of infectious diseases (eg, human
papillomay virus vaccine) within 4 weeks of study drug administration. The inactivated
seasonal influenza vaccine can be given to participants before treatment and while on
therapy without restriction. Influenza vaccines containing live virus or other clinically
indicated vaccinations for infectious diseases (ie, pneumovax, varicella, etc) may be
permitted, but must be discussed with the BMS Medical Monitor and may require a study
drug washout period prior to and after administration of vaccine.
5) Physical and Laboratories Test Findings
a) Participants with abnormal serum chemistry values, which in the opinion of the
investigator is considered to be clinically significant, will be excluded from the study.
This will include participants who show clinical signs and symptoms related to their
abnormal serum chemistry values, as well as participants whose serum chemistry values
are asymptomatic but clinically significant (eg, hypokalemia or hyponatremia).
b) Evidence of coagulopathy or bleeding diathesis
c) Ascites needing paracentesis or medical management
d) Peripheral Neuropathy greater than Grade 1
e) Albumin less than 3 g/dL
f) Evidence of organ dysfunction or any clinically significant deviation from normal in
physical examination, vital signs, ECG, or clinical laboratory determinations beyond
what is consistent with the target population
6) Allergies and Adverse Drug Reactions
a) Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and
Tween 80 (polysorbate 80)
b) History of allergy to study treatments or any of its components of the study arm that
participant is enrolling
7) Other Exclusion Criteria
a) Not applicable per Revised Protocol 02 - Consumption of non-pasteurized milk while on
study drug and for 30 days after discontinuing study drug
b) Pregnant or breastfeeding
c) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific
circumstances a person who has been imprisoned may be included or permitted to
continue as a participant. Strict conditions apply and BMS approval is required.
d) Participants who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness
The Estimated Number of Participants
-
Taiwan
10 participants
-
Global
160 participants
