Overview of clinical trials for metastatic triple-negative breast cancer by Sara M. Tolaney, MD, MPH, Associate Director and Associate Director of Clinical Research at Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute.

1. Clinical Trials for
Metastatic Triple-Negative Breast Cancer
Sara M. Tolaney, MD, MPH
Associate Director Clinical Research

2. Clinical Trials: Why Participate?
• You have a chance to help others and improve cancer care
• You can expand the number of treatment options you
have
• Many trials involve targeted therapies with the goal of
improved effectiveness and decreased side effects
• If a new treatment is proven to work and you are
receiving it, you may be among the first to benefit
2

3. Clinical Trials: FAQs
• When should I consider a clinical trial?
 Clinical trials may be an option for you as early as the first treatment you receive
for metastatic breast cancer, but may also be an option further into the course of
your disease.
 If you are interested in trials, getting connected early to a treatment team who can
help identify potential trials for you is key.
• Will I have to pay more to be on a trial?
 All normal procedures are billed to insurance; anything beyond normal care is paid
for by the trial. There should be no “upcharge” for being in a trial
• Will I know what medicine I am getting? I don’t want a placebo.
 In most trials, both patient and provider know exactly what treatment is being
given.
 Some larger trials use randomization and placebos, and in some cases neither
patient nor provider know identity of study drug.
 But in almost every trial with placebo, at minimum a patient receives best standard
of care.

4. Clinical Trials for Metastatic TNBC
• There are many clinical trials open focusing on TNBC.
• Clinical trials are testing the safety and effectiveness of new
treatments.
• Today we will provide some highlights of a few of the available
trials.
• These treatments are provided as part of trials because we do
not understand whether they are the same, better, or worse,
than standard treatments.
• Trial treatments may also have different side effects than
standard treatments.
• Each trial has specific requirements for patients to be included.
4

5. • There are three main subtypes of breast
cancer
 ER positive
 HER2 positive
 Triple negative
• Within these, there are other ways to
further sub-divide breast cancers
• Oncologists use the breast cancer subtype to
guide the kinds of treatments to recommend
• Clinical trials often will focus on specific
subtypes
Breast Cancer Subtypes

6. “Triple Negative” Breast Cancer (TNBC)
• Defined as negative for estrogen, progesterone, and HER2 receptors
• Represents about 15% of all breast cancer
• More likely to present in younger women and in women of African
ancestry
• May be associated with an inherited mutation in BRCA1
 National guidelines recommend consideration of genetic testing in women
younger than age 60 with TNBC, regardless of family history
 But--most patients with triple negative breast cancer do not carry a
hereditary BRCA1 mutation

7. • PD-1 is an inhibitory receptor
expressed on immune cells
• Tumors express PD-L1 to evade
immune surveillance
• Interaction between PD-L1 and
PD-1 puts the brakes on the
immune cells
• Antibodies against either receptor
takes the brakes off
Immunotherapy for TNBC
* Thompson et al. 2006; Hamanishi et al. 2007; Okazaki and Honjo 2007; Hino et al. 2010
MHC1
PD-L2
B7-1
PD-L1
TCR
PD-1
CD28
B7-1
Antigen Presenting Cell
T cell
PD-L1
Activation
** Dry, J.R. et al Cancer Research 2010 70;2264; Hoeflich K.P. et al Clin Cancer Res 2009 15(14): 4649
Suppl data.
Keir, ME et al 2008. Annu. Rev. Immunol. 26:677

8. A randomized phase II trial of carboplatin with or
without nivolumab in first- or second-line metastatic
triple-negative breast cancer

9. Carboplatin +/- Nivolumab
9

10. Key Eligibility Criteria
• ER and PR ≤ 1% by IHC, and HER2-negative status per ASCO/CAP guidelines.
• Measurable or evaluable disease by RECIST version 1.1.
• Participants must agree to undergo a research biopsy, if safely accessible, at
baseline.
• Normal organ and marrow function as defined per protocol
• Prior chemotherapy: 0-1 prior chemotherapeutic regimens for MBC; off
treatment for at least 14 days prior to registration
No prior platinum in the metastatic setting is allowed. Prior platinum in
the neo/adjuvant setting is permissible, if ≥ 12 months elapsed since end
of adjuvant therapy to development of metastatic disease. If patient
recurs within 12 months of neo/adjuvant therapy, this will be counted as
one line of therapy for metastatic disease.
10

11. A few examples of other immunotherapy
combination studies
• Cabozantinib + nivolumab
 Combines a targeted drug that inhibits angiogenesis with an
antibody against PD1
• Eribulin + pembrolizumab
 Combines chemotherapy with an antibody against PD-1
• Vaccine + pembrolizumab
 Combines a peptide vaccine with an antibody against PD-1
11

12. Drug-Antibody Conjugates for TNBC
12
1. Antibody specific for an
antigen on the surface of
tumor cells
2. Antibody is linked to a
chemotherapy drug
3. Chemotherapy agent is
released inside the cancer
cell

13. Phase 2 study of
IMMU-132 demonstrated
activity in pretreated
patients
• Response rate=30%
in patients with a
median of 5 prior
therapies since their
diagnosis
13

14. Phase 3 IMMU-132 vs TPC

15. Key Eligibility Criteria
• TNBC per ASCO/CAP criteria, based on the most recent analyzed biopsy or other pathology
specimen
• Measurable disease by CT or MRI as per RECIST 1.1. Bone-only disease is not permitted
• Brain MRI must be done for patients with brain metastasis and patient must have had stable
CNS disease for at least 4 weeks
• Refractory to or relapsed after >2 prior standard of care chemotherapy regimens for
unresectable, locally advanced or metastatic BC.
 Regimens will qualify regardless of triple-negative status at the time they were given.
 No upper limit in the number of prior chemotherapies.
 Earlier adjuvant or neoadjuvant therapy for more limited disease will qualify as one of
the required prior regimens if the development of unresectable, locally advanced or
metastatic disease occurred within a 12-month period of time after completion of
chemotherapy
• All patients must have been previously treated with a taxane
• Eligible for 1 of the chemo options (Eribulin, capecitabine, gemcitabine, or vinorelbine) per
investigator

16. Other Trial Options
• Many other clinical trial options for TNBC
 DNA-damaging agents
 Cell cycle inhibitors
 Other drug antibody conjugates (LIV1)
 Trials specific for patients with BRCA mutations
16

17. How do I find a clinical trial?
• Talk with your oncologist and let her/him know you may be interested in
clinical trials.
• Consider a consultation at an academic cancer center.
• https://www.cancer.gov/research/nci-role/cancer-centers
• We are also happy to see new patients at Dana-Farber – (617) 632-2175.
• Consider web resources.
• Breastcancertrials.org
https://www.breastcancertrials.org/bct_nation/home.seam
• Metastatic Breast Cancer Alliance http://www.mbcalliance.org/clinical-
trials-in-metastatic-breast-cancer
• Best to ask your oncologist what makes sense for you and to know that this can
change over time.
17

18. How Can We Make Progress?
Support Clinical Trials!
• “One reason I chose to participate in a clinical trial
was to help women with triple-negative breast
cancer. It is thanks to women who have enrolled in
clinical trials that we have the treatments that give
us hope.”
 Natalia (LBBC, Guide to Understanding TNBC)