Inclusion Criteria
1. Locally advanced or metastatic breast cancer of hormone receptor (HR)+, including
estrogen receptor (ER) and progesterone receptor, human epidermal growth factor
receptor 2 (HER2)+, or triple-negative breast cancer (TNBC) histology (based on local
review, no central pathology review required for enrollment).
2. ER, progesterone receptor, and HER2 status is known and documented per ASCO/CAP
guidelines.
3. Measurable disease at time of screening in accordance with RECIST v1.1 criteria.
Subjects who no longer have measurable disease at time of disease re-baseline prior to
lymphodepletion start will be allowed to proceed with study treatment but will not be
considered evaluable for efficacy.
4. Adequate time has elapsed between the last dose of prior therapies and planned date of
leukapheresis. Adequate time is 4 half-lives of prior therapies or 28 days, whichever is
shorter. For investigational products for which a half-life has not been established, at
least 28 days must have elapsed. For anti-PD1/PDL1 based therapies, at least 28 days
must have elapsed. For prior radiation, at least 2 weeks must have elapsed.
5. Women or men age ≥18 years of age at time of consent.
6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
7. Estimated life expectancy ≥12 weeks from anticipated first dose of study treatment.
8. Subjects must provide a biopsy sample obtained during the screening period, following
the end of the most recent prior line of therapy. For subjects without an accessible site of
disease (site of disease wherein collection of biopsy would present risk to the subject)
then a formalin-fixed paraffin-embedded (FFPE) archival tumor sample obtained
following the most recent prior line of therapy (no older than 6 months prior to consent)
may be provided. Subjects without archival tissue or biopsy-accessible site of disease
may still be eligible for study after discussion with Sponsor.
9. Evidence of a personally signed and dated informed consent document indicating that the
subject has been informed of all pertinent aspects of this study.
10. Subjects must have unresectable locally advanced or metastatic breast cancer that is
refractory or relapsed. Subjects must have exhausted all standard of care (SoC) therapy
options available within the locally advanced or metastatic setting that have shown
documented improvement in overall survival, which must include the below minimum
exposures. Being intolerant of, unsuitable for, or having refused SoC therapy options
(even minimums defined in a through e) will count as exposure for the purpose of
eligibility; all exposure must be documented by the Investigator. There is no maximum
number of prior exposure or lines of systemic treatment regimens.
a. TNBC subjects: In the metastatic setting, subjects must have had exposure to at
least 2 prior therapies, for example cytotoxic chemotherapy, anti-PD/PD-L1 agent
for Combined Positive Score (CPS) >10, or ADCs.
b. HR positive, HER-2 negative subjects: In the metastatic setting, exposure to at
least 2 lines of therapy, which must include 1 endocrine therapy, and at least 1 additional therapy, for example chemotherapy or ADCs. Subjects with a PIK3CA
Protocol CBR-sCAR461-3001 V2.0, 17 Oct 2024 CONFIDENTIAL Page 29 of 90 or AKT1 activating mutation or PTEN alterations must have had exposure to at
least 1 targeted therapy, for example alpelisib or capivesertib.
c. HR positive or negative, HER2 positive subjects: Exposure to at least 2 HER2-
directed therapy in the metastatic setting, for example trastuzumab and/or
pertuzumab, oral HER2 tyrosine kinase inhibitors, or ADCs.
d. HR positive or negative, HER2-low subjects, with HER2-low defined as HER2 Immunohistochemistry (IHC) score of 1+ or 2+ and no detectable ERBB2 amplification: Prior exposure to trastuzumab deruxtecan in the metastatic setting.
e. Subjects BRCA1/2, irrespective of HR status: prior exposure to PARP inhibitor in
the metastatic setting.
11. Subjects with known brain metastasis may be enrolled if they are stable. Stable is defined
as asymptomatic and not requiring treatment for at least 4 weeks prior to informed
consent and/or previously treated but not requiring further treatment for at least 4 weeks
prior to date of informed consent. Subjects with known brain metastasis must have
imaging conducted during screening to confirm no treatment of lesions is indicated (see
SoA for guidance). Subjects with no history of brain metastasis but who have clinical
indications/symptoms must have brain imaging conducted during screening; if new
occurrence of brain metastasis is discovered then subjects may be allowed to participate
once determined to be stable and meet the definition in this criterion (rescreening may be
required to ensure subject meets eligibility timelines outlined in the SoA). Subjects who
do not have a history of brain metastases and who do not have any clinical
indication/symptoms of brain metastasis are not required to undergo head/brain imaging
during screening. Please see Section 8.11.1 for additional details.
12. Adequate hematological function, including all of the following:
a. Absolute neutrophil count (ANC) ≥1,000/mm3 (≥1.5 x 109/L)
b. Absolute lymphocyte count ≥100/mm3 c. Platelet count ≥100,000/mm3 (≥100 x 109/L)
d. Hemoglobin >8.0 g/dL
13. Adequate renal function, including all of the following:
a. Not dialysis dependent
b. Estimated creatinine clearance ≥50 mL/min as calculated using the method
standard for the institution (including 24-hour creatinine clearance).
14. Adequate liver function, including all of the following:
a. Aspartate and alanine aminotransferase (AST and ALT) ≤3x upper limit of
normal (ULN); up to 5x ULN allowed in subjects for whom elevation is due to
disease under study (i.e., subjects with liver metastasis) and total bilirubin is
within normal limits.
b. Total bilirubin ≤1.5 mg/dL, except in subjects with Gilbert’s Syndrome who must
have a total bilirubin <3.0 mg/dL.
15. Serology
a. Hepatitis B subjects with negative hepatitis B surface antigen (HbsAg) and
positive hepatitis B core antibody (HbcAB), and/or positive hepatitis B surface
antibody (HbsAB) and subjects who are immune due to natural infection or
vaccination are permitted to be enrolled.
b. Subjects with a history of hepatitis B virus (HBV) infection (without active
infection at Screening) are eligible if there is no evidence of active HBV infection
Protocol CBR-sCAR461-3001 V2.0, 17 Oct 2024 CONFIDENTIAL Page 30 of 90 AND must receive anti- HBV prophylaxis while receiving study drug(s) and for 5 months after the last dose of study drug(s). The choice of anti-HBV therapy may
be made per local standard of care.
c. Hepatitis B subjects with positive HbsAg and positive HbcAg indicate either
acute or chronic, active disease. These subjects are not eligible to participate in
the study.
d. Subjects positive for hepatitis C virus (HCV) antibody, negative (undetectable)
for viral load by polymerase chain reaction (PCR) who are treated and cured are
eligible * Note: Subjects should be on prophylactic treatment as clinically
indicated.
16. Adequate pulmonary function, defined as Grade ≤1 dyspnea and saturated oxygen (SaO2)
≥92% on room air.
17. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) of ≥50%
as assessed by echocardiogram or multigated acquisition (MUGA) scan. There should be
no evidence of pericardial effusion requiring treatment.
18. Resolved AEs of any prior therapy to either baseline or CTCAE Grade ≤1 with the
exception of those AEs not constituting a safety risk per Investigator’s judgement (e.g.,
alopecia, vitiligo). In the judgment of the Investigator, recovered from any major surgery
prior to consent that would make the subject inappropriate for entry into the study.
19. For all female subjects of childbearing potential, a negative serum pregnancy test.
20. Female of childbearing potential must agree to practice a protocol-specified method of
effective birth control from time of signing of informed consent through 1 year following
the last dose of Investigational Product received on study. Female subjects of non-
childbearing potential do not need to use birth control.
21. Women who are not pregnant, breastfeeding, or considering becoming pregnant from
signing of informed consent through 1 year following the last dose of Investigational
Product received on study.
22. If a male is sexually active with a female partner(s) of childbearing potential, he must
agree from signing of informed consent through 1 year following the last dose of
Investigational Product received on study to practice protocol-specified contraception.
23. Men who are not considering fathering a child or donating sperm from signing of
informed consent through 1 year after the last dose of Investigational Product received on
study.
24. Subjects who are on skeletal protective therapies, such as bisphosphonates or denosumab,
may continue during study treatment provided they have started >14 days prior to consent
and are on a stable dose in the opinion of the investigator.
25. Subjects who are receiving ovarian functional suppression may continue during study
treatment provided they have started >14 days prior to consent and are on a stable dose in
the opinion of the investigator.
26. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and
other procedures.
27. Adequate venous access and no other contraindications for leukapheresis.

Exclusion Criteria
1. History of a clinically significant infection (including sepsis, pneumonia, bacteremia,
fungal, viral, and opportunistic infections) within 4 weeks prior to consent, which in the
opinion of the Investigator may compromise the safety of the subject in the study.
2. Active bacterial, viral, and/or fungal infection including tuberculosis, HBV, HCV,
Epstein-Barr Virus (EBV), cytomegalovirus (CMV), herpes, or human
immunodeficiency virus (HIV). See SoA for Infection Testing requirements.
3. Prior allogeneic stem cell transplant.
4. Prior lentiviral- or retroviral-based therapy including CAR-T cell therapy.
5. Prior lymphodepleting or T-cell cytotoxic therapy within 3 months of enrollment; some
therapies may not be exclusionary (those that will not limit CLBR001 manufacture)
discussion with Sponsor required.
6. Subjects receiving live (attenuated) vaccines within 4 weeks of consent or known need
for live vaccine within 12 months after administration of CLBR001.
7. History of any one of the following cardiovascular conditions within the past 6 months:
Class III or IV heart failure as defined by the New York Heart Association (NYHA),
cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically
significant cardiac disease.
8. Subjects with a prior history or concurrent malignancy whose natural history or treatment
has the potential to interfere with either the safety or efficacy assessment of the
investigational regimen. (Subjects with prior history or concurrent malignancy that does
not have the potential to interfere with safety and efficacy assessments may be included
after discussion with Sponsor).
9. Any other acute or chronic medical or psychiatric condition that may increase the risk
associated with study participation or investigational product administration or that, in the
judgment of the Investigator, would make the subject inappropriate for entry into the
study.
10. HIV-1 and HIV-2 antibody-positive subjects.
11. Prior PRLR-directed therapy