Our guest speaker Lee Gravatt Wilke, MD, Senior Medical Director at the University of Wisconsin School of Medicine and Public Health, explains the current state of vaccine clinical trials in breast cancer followed by a review of the STEMVAC trial, design of the vaccine, and the current state of the accrual and next steps.

1. Vaccines:
Will they become a form of Secondary
and Primary Breast Cancer
Prevention?
Lee G. Wilke, MD
Professor of Surgery
Hendricks Chair in Breast Cancer Surgery Research
Senior Medical Director, Clinical Cancer Services

2. Disclosures
Lee Wilke: (not discussed in today’s talk)
• Founder, Minority Stock Owner – Elucent Medical
• Principal Investigator (no salary support) – Perimeter Medical
I am not a Vaccine Expert – but as the Site Principal Investigator for the
STEMVAC trial have learned an immense amount from:
Dr (Mary) Nora Disis; University of Washington, Seattle
Cancer Vaccine Institute Director;
Professor of Medicine and Adjunct Professor of
Pathology and Obstetrics and Gynecology
Helen B. Slonaker Endowed Professorship
American Cancer Society Clinical Research Professor

3. What is Cancer?

4. Many “Factors” Influence Cancerous Growth
https://www.cancer.gov/about-cancer/understanding/what-is-cancer

6. National Imperative to Reduce Inequities

7. Development of
New Cancer
Treatments
Clinical Trials
Safety and
Dosing
Compare New
to Standard
Therapy
Efficacy &
Short term
outcomes

8. Evolution of Axillary Surgery/Clinical Trials
Adapted from T King, MD; M Morrow MD and E Mittendorf, MD
1960-1980s 1990s 2000s
ALND
SLNB for
cN0
SLNB ± RT
for 1-2+ SLN
2010s
SLNB for cN1
after NAC

9. Timeline of drug development in breast
cancer
tamoxifen alpelisib
Sacituzumab govitecan
Trastuzumab dertuxtecan
Ado-trastuzumab emtansine
AIs
Pembrolizumab and others
faslodex
lapatinib
trastuzumab
elacestrant
doxorubicin paclitaxel
capecitabine
gemcitabine
nab-paclitaxel
ixabepilone eribulin
Chemo
1980s
1970s 1990s 2000s 2010s 2020s
Targeted
ADCs
Immunotherapy
PARPi
CDK4/6i
Synthetic lethal

10. The profound impact of vaccines on public health

11. The immune system can recognize & respond to cancer
Eliciting the right kind of immune response
TYPE I RESPONSE
Immune response
needed to kill cancer
CD8 T Cells CD4 T Cells
TYPE II RESPONSE
Immune response promotes
cancer growth
B Cells Regulatory
T Cells

13. Demaria, O., Cornen, S., Daëron, M. et al. Harnessing
innate immunity in cancer therapy. Nature 574, 45–56 (2019)
Key Components:
1. “Immunogenic protein” = Antigen
• Specific to the Cancer
• Will be recognized as “foreign”
by the patient’s immune system
2. Vaccine Technology
• Shows the Antigen to the
Immune System
3. Adjuvant or “Booster” to augment
the immune system against the
Antigen

14. Antigen (Protein) Example – HER 2
• Overexpressed protein in 30% of
breast cancers
• Study of
• 100 volunteer women
• 100 untreated patients with ductal
carcinoma in situ (DCIS)
• 500 with invasive breast cancer
• High levels of HER2-specifc
antibodies in the blood were
associated with reduced risk of
DCIS or invasive cancer.
• High level of HER2-specifc
antibodies was independently
associated with recurrence free
survival Tabuchi et al. Breast Ca Res
Treatment 2016; 157: 55-63

15. “Present” the Antigen
Lopes et al. Journal of Experimental & Clinical Cancer
Research (2019) 38:146

16. “Package” the Antigen
Pulendran B et al, Nature Reviews Drug Discovery
20, p454–475 (2021)

17. “Therapeutic” Vaccine Trials
Antigen Number/Type of
Patients
Schedule of
Treatments
Outcomes
Theratope
(Miles D et al
2011 Oncologist
16:1092)
STn-KLH vs KLH
(placebo)
1023/ Metastatic Randomized
9 injections then q
12 week
No differences in
overall (22.3 vs
23.1 months) and
recurrence free
survival
OBI -822
(Huang CS et al
2020 J Immuno
Cancer 8
e000342)
GLOB H epitope
with KLH vs KLH
(placebo)
348 /Metastatic Randomized
9 injections
No differences in
progression free
survival (7.6mo
vaccine vs 9.2 mo
placebo)
PRESENT
(Mittendorf EA et
al 2019 Clin Can
Res 25: 4248)
Neli-pepimut HER 2
Class 1A restricted
peptide vaccine vs
placebo (with GM-
CSF)
758/Her 2 Low 1+
or 2+; T1-T3; Node
positive
Randomized
Monthly x 6 then q
6 months to 36
months
Stopped early due
to “futility” – no
difference in
Disease free
survival

18. What Went Wrong… and Right?
• Use of Single Antigens that may not have been as “Immunogenic”
• Majority of Patients had Advanced or Metastatic Cancer
• Minimal “Long Term Immunologic Memory”
• Need to Combine Treatments – Vaccine plus Chemotherapy vs
Immunotherapy
• Minimal Toxicity – primarily injection reactions
• 9% Response Rate/Meta-analysis of all Trials (21 studies; 428
patients)
Disis M et al. Breast Cancer Research and Treatment (2022) 191:481–489

19. We are at a tipping point for cancer vaccines
New vaccine technology
makes immunization
more effective
3
We know the type of
immune response we
need to kill cancer
1
We know what parts of a
cancer can stimulate the
immune system
2

20. “Infectious Disease Approach” – Immunologic Memory
Phase II trial of Dendritic Cell
primed peptide HER2 vaccine in
patients with HER 2 positive DCIS
• Injection into groin lymph nodes
prior to surgery for 4 weeks
• 18.5% or 5/27 patients had no
residual DCIS at surgery
• 11/22 had no detectable HER 2
expression
• (Sharma A et al. Cancer 2012;
118: 4354)
Phase II trial of HER 2 derived MHC
Class I peptide E75 (Nelipepimut-S)
with GM-CSF
• Randomized to vaccine with GM-
CSF (9 patients) or GM-CSF alone (4
patients)
• 2 vaccine doses prior to surgery
• (O’Shea AE, et al. Cancer Prev Res
2023; 16: 333)

21. (UW Vaccine Institute) technology allows development
of vaccines that elicit a strong anti-cancer response
 Treat Cancer
 Prevent Cancer Recurrence
 Prevent cancer from occurring in the first place
Developing DNA vaccines to:

22. Targeting cancer stem cells to prevent cancer:
STEMVAC vaccination
Effective in preventing
breast cancer in mice
Age (days)
Percent
Tumor
Free
0 100 200 300 400 500
0
25
50
75
100
****
STEMVAC
Cancer Stem Cell
Resistance to therapy
Recurrence
Metastasis
STEMVAC DNA vaccine
Targets 5 stem cell proteins

23. STEMVAC vaccine showed a strong immune
response in stage III/IV breast cancer patients
Clinical Trial
Phase I, dose escalation
3 doses of vaccine
Stage III/IV Breast Cancer
Hormone receptor positive or
Triple Negative
30 patients (10 per dose)
3 vaccines 1 month apart, id
Boosters at 3 and 9 months
 We detected an immune response to all 5 stem cell proteins
 Boosters increase level of response
 Very high levels of STEMVAC immunity

24. STEMVAC may be effective for many other cancers
A Phase II Randomized Study of Safety and Efficacy of
a Multiple Antigen Vaccine (STEMVAC) in Non-
Squamous Non-Small-Cell Lung Cancer Patients
NCT05242965
A Phase II Trial of the Immunogenicity and Efficacy of a
DNA Plasmid Based Vaccine STEMVAC in Participants
with Non-Metastatic Triple Negative Breast Cancer
NCT05455658

25. STEMVAC
• Phase II Trial
• Oversight by NCI Division of
Cancer Prevention
• Monthly Injection x 3 then 2
boosters at 6 and 12 months
• Primary Endpoint:
• Immune response to the antigen
• Incidence and magnitude
• 22 (of 33) patients on trial with 6
patients completing all injections
and in follow-up

26. Questions/Thank you!