Lay Description

This is an international, multicenter, open-label, randomized, Phase 3 study in patients with locally advanced, inoperable, or metastatic triple-negative breast cancer (mTNBC) who have not received previous therapy for advanced disease and whose tumors are PD-L1 positive (defined using the PD-L1 IHC 22C3 assay as tumors with a combined positive score [CPS] ≥ 10) at screening.


  • Cancers and Other Neoplasms
IRB Number
NCT Number registration not required
Open to Enrollment


Eligible Ages
18 and over
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

Female or male patients, regardless of race and/or ethnic group, who are18 years of age or
older, able to understand and give written informed consent
2) Patients with locally advanced inoperable or metastatic TNBC who have not received
previous systemic therapy for advanced disease and whose tumors are PD-L1 positive at
a) Patients must have completed treatment for Stage I to III breast cancer, if indicated, and
≥ 6 months must have elapsed between completion of treatment with curative intent
(eg, date of primary breast cancer surgery or date of last (neo)adjuvant chemotherapy
administration [including anti-PD-(L)1 treatment], whichever occurred last) and first
documented local or distant disease recurrence. Dates of postoperative radiotherapy are not
included in this calculation. Prior use of an anti-PD(L)1 agent in the curative TNBC setting
is permitted.
i) Patients who received taxane, gemcitabine, or platinum agents in the (neo)adjuvant
setting can be treated with same class of chemotherapy (taxane or
gemcitabine/carboplatin) if ≥ 12 months have elapsed between the completion of
treatment with curative intent (eg, date of primary breast tumor surgery or date of last
(neo)adjuvant chemotherapy administration, whichever occurred last) and first
documented local or distant disease recurrence.
ii) Patients enrolled should have received prior anthracycline in the (neo)adjuvant setting
or be considered not eligible for anthracyclines as assessed by the treating physician.
b) Patients presenting with de novo metastatic TNBC are eligible for this study.
c) TNBC status and tumor PD-L1 CPS will be confirmed centrally on a recent or archival
tumor specimen.
Patients must have histologically or cytologically documented TNBC, according to
current ASCO/CAP criteria, defined as negative for ER, progesterone receptor, and
HER2 {Allison 2020, Wolff 2018}. Patients initially diagnosed with hormone
receptor-positive or HER2-positive breast cancer must have central confirmation of
TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis site prior
to study entry.
Tumor CPS ≥ 10 using the PD-L1 IHC 22C3 assay will be required for eligibility.
d) Patients must have measurable disease by CT or MRI as per RECIST Version 1.1 criteria
(Appendix 6) as evaluated locally. Tumor lesions situated in a previously irradiated area
are considered measurable if unequivocal progression has been documented in such lesions
since radiation.
3) Have provided representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in
blocks (preferably) or have at least 20 to 25 freshly sectioned unstained slides from fresh
biopsy tissue (preferred) or archival tissue block for central testing of ER, progesterone
receptor, HER2, PD-L1, Trop-2, and additional biomarker testing. A baseline biopsy is
required if archival tissue is not available and this procedure must be performed prior to the
first dose of study treatment and after the patient provides written informed consent. Fine
needle aspirates and bone biopsies are not suitable samples.
Note: Tumor tissue quality must be confirmed by the central laboratory. Submission of
another tumor specimen may be required if provided specimen is not adequate for
4) ECOG performance status score of 0 or 1 (Appendix 5).
5) Life expectancy ≥ 3 months.
6) Recovered from major surgery for ≥ 2 weeks.
7) Adequate hematologic counts without transfusional or growth factor support within 2 weeks
of study treatment initiations (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets
≥ 100,000/μL).
8) Adequate hepatic function (bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN
if known liver metastases, and serum albumin > 3 g/dL).
9) Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation {Cockcroft
10) International normalized ratio (INR)/PT and PTT or aPTT ≤ 1.5 ULN unless patient is
currently receiving therapeutic anticoagulant therapy.
11) Male patients and female patients of childbearing potential who engage in heterosexual
intercourse must agree to use protocol-specified method(s) of contraception as described in
Appendix 3.
12) Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV
infection/disease defined as:
a) Patients on ART must have a CD4+ T-cell count ≥ 350 cells/mm3 at time of screening.
b) Patients on ART must have achieved and maintained virologic suppression defined as
confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below
the limit of detection) using the locally available assay at the time of screening and for at
least 12 weeks prior to screening.
c) Patients on ART must have been on a stable regimen, without changes in drugs or dose
modification, for at least 4 weeks prior to study entry (Day 1).
d) The combination ART regimen must not contain any medications that may interfere with
SN-38 metabolism

Exclusion Criteria

1) Positive serum pregnancy test (Appendix 3) or women who are lactating.
2) Known or severe (≥ Grade 3) hypersensitivity or allergy to SG, pembrolizumab, and/or the
chemotherapy regimen of choice in the TPC arm (eg, nab-paclitaxel, paclitaxel, gemcitabine,
or carboplatin), their metabolites, or formulation excipient.
3) Have received prior therapy with an agent directed to another stimulatory or coinhibitory
T-cell receptor (eg, CTLA-4, OX-40, CD137)
4) Requirement for ongoing therapy with or prior use of any prohibited medications listed in
Section 5.6.1.
5) Patients may not have received systemic anticancer treatment within the previous 6 months
or radiation therapy within 2 weeks prior to enrollment. Patients must have recovered from
AEs due to a previously administered agent to ≤ Grade 1 or baseline at the time of study
 Note: patients with ≤ Grade 2 neuropathy or any grade alopecia are an exception to this
criterion and will qualify for the study. Patients with endocrine-related AEs Grade ≤2
requiring treatment or hormone replacement may be eligible.
 Note: if patients received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
6) Patients may not be participating in a study with an investigational agent or investigational
device within 4 weeks prior to randomization. Patients participating in observational studies
are eligible.
7) Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing
a topoisomerase inhibitor.
8) Have an active second malignancy.
Note: patients with a history of malignancy that has been completely treated, with no
evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured
tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed
complete excision of carcinoma in situ, or similar) are allowed to enroll.
9) Have known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate (with the
exception of those treated with chemotherapy) provided they have stable CNS disease
(defined as radiographic stability demonstrated with a minimum of 2 post-treatment brain
imaging assessments; one performed during screening) for at least 4 weeks prior to
enrollment and all neurologic symptoms have returned to baseline, have no evidence of new
or enlarging brain metastases, and have also been clinically stable for at least 2 weeks while
taking ≤ 10 mg/day of prednisone or its equivalent. All patients with carcinomatous
meningitis are excluded regardless of clinical stability.
10) Have undergone an allogenic tissue or solid organ transplant.
11) Met any of the following criteria for cardiac disease:
a) Myocardial infarction or unstable angina pectoris within 6 months of enrollment.
b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular
fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring
antiarrhythmic medications (except for atrial fibrillation that is well controlled with
antiarrhythmic medication); history of QT interval prolongation.
c) New York Heart Association Class III or greater congestive heart failure or known left
ventricular ejection fraction of < 40%.
12) Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI
perforation within 6 months of enrollment.
13) Have active serious infection requiring systemic antimicrobial therapy.
14) Patients positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric
Castleman Disease.
15) Have active HBV (defined as having a positive HBsAg test) or HCV.
a) For patients with a history of HBV infection, a hepatitis B core antibody test should be
conducted at screening. If positive, hepatitis B DNA testing will be performed and if active
HBV infection is ruled out, the patient may be eligible.
b) Patients who are HCV antibody positive with undetectable HCV viral load may be eligible.
16) Have other concurrent medical or psychiatric conditions that, in the investigator’s opinion,
may be likely to confound study interpretation or prevent completion of study procedures and
follow-up examinations.
17) Has a diagnosis of immunodeficiency or receiving systemic corticosteroid therapy (higher
than physiologic doses) ≥ 10 mg of prednisone per day or equivalent] or any other form of
immunosuppressive therapy within 14 days prior to randomization.
18) Has received a live or live-attenuated vaccine within 30 days prior to randomization.
Administration of killed vaccines are allowed.
19) Has an active autoimmune disease that has required systemic treatment in the past 2 years
(eg, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Replacement therapy (eg, thyroxine, insulin, physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is
20) Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or
has current pneumonitis/interstitial lung disease.
21) Has received prior radiotherapy within 2 weeks of start of study intervention. Patients must
have recovered from all radiation-related toxicities, not require corticosteroids, and not have
had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (2 weeks
of radiotherapy) to non-CNS disease.

Study Design

Arm Groups

Study Contact

Frances Crawford
(210) 450-5037

Sonia Creighton
(210) 450-1366

Myrna Montenegro
(210) 450-5954

Courtney Nichols
(210) 450-1794

Mailbox Ctrc Regulatory Affairs

Kathleen Rodriguez
(210) 450-1365

Benjamin Schleif
(210) 450-1366

Morgan Seekatz
(210) 450-1133

Principal Investigator
Virginia Kaklamani