Anil K. Sood, M.D., Professor Vice Chair, Translational Research Departments of Gynecologic Oncology and Cancer Biology Co-Director, Center for RNAi and Non-Coding RNA Director, Blanton-Davis Ovarian Cancer Research Program

1. Launching the Women’s Cancer Moonshot
Anil K. Sood, M.D., Professor
Vice Chair, Translational Research
Departments of Gynecologic Oncology and Cancer Biology
Co-Director, Center for RNAi and Non-Coding RNA
Director, Blanton-Davis Ovarian Cancer Research Program

2. Concept: Make the Impossible…Possible
John F. Kennedy Moon Speech, Rice Stadium
September 12, 1962

3. Strategic Initiative
Cancer Moon Shot Program
Can we systematically harness the full potential of today’s
technology, major conceptual advances and our critical
mass and collaborative networks to more rapidly drive
progress in the field?

4. Why a Combined Ovarian and Breast
Cancer Moonshot?
• Medical Need and Impact
• Deep knowledge and molecular characterization
• Common predisposition factors
Common concepts for risk, prevention, screening and
survivorship
• Molecular, biological and clinical commonalities
• Cross pollination

5. Flagship Projects: THE START
•Will have immediate impact on patient outcomes
•Can be implemented without “new knowledge”
•Broadly applicable across disease
•Engage the community: Faculty, patients and outreach
•Efficiencies offered by Moon Shot Platforms

6. Germline BRCA-1 and -2 testing
(>10% will be positive)
Active Outreach
Screening
Prevention
Offer genetic testing to all patients
with HGSOC or TNBC
Flagship project 1a: Impacting the Family

7. Goal:
80% decrease in deaths in
family members over 5
years
Flagship project 1a: Impacting the Family

8. 20-50% of patients will have a
defect in the function of BRCA1 or
BRCA2
PARP-inhibitor based therapy
Offer genetic testing to all patients
with HGSOC or TNBC
Flagship project 1b: Impacting the Patient

9. Flagship Project 2: Personalizing Surgical Therapy
Impact of residual disease: Overall survival
Dubois et al, Cancer, 2009: Mar 15; 115(6): 1234-44

10. Opportunity For Quality Improvement:
Personalized Surgical Therapy
Women w/ suspected
ovarian cancer
Primary
Assessment
Intraoperative
agreement
Laparoscopy:
Validated score
R0 not feasible
Neo-adjuvant
chemotherapy
R0 feasible
Primary tumor
reductive
surgery
Tissue

11. Primary cytoreduction 20% 87% (n=50)
NACT → Interval cytoreduction 60% 76% (n=14)
Surgical Outcomes (R0 Rates) since
Implementation of FP2A
Pre-
implementation
Post-
implementation
*Major effort focused on R0 resection included education, clinical
retreats, and engaging other specialties
*Compliance is >95%

12. NEXT STEPS
• Development of novel clinical trials
– Window of opportunity trials
– Novel biologic combinations plus standard neoadjuvant
chemotherapy
• Comparative effectiveness assessment
• Expansion into other institutions
– Sister Institution Network

13. NEW MOONSHOT PROJECTS-FP2B OVARIAN
FlagshipProject2
LSC
Score <8
FP2b Phase 0 “Window” trials
1-2 wks
Single Agents
“POSITION” Trial
Debulking
Tissue acquisition
Novel therapy
vs.
Std therapy
Tissue acquisition
e.g., BMN-673
Score >8
FP2b Phase Ib-2 Treatment Trials
NACT
Pac/Carbo + novel Debulking
Adjuvant
Pac/Carbo + novel
Tissue acquisition
e.g., SPD535

14. PROJECT 2A/B – AGENTS
• PARPi: BMN-673, olaparib, others
• PI3K pathway: BKM120, AZD2014
• Angiogenesis: Dll4 (demcizumab), TAMs (zoledronic
acid, AC708)
• Immune: PD-1 (MK-3475)
• P53: MK-1775, COTI-2
• Platelets: SPD535
• Others: Prolanta (PrL), KPT-330

15. Other Deliverables
• Translational biology
• P53 based approaches – synthetic lethality
• Adaptive changes to therapy
• Rational combination therapy (e.g., new combinations of kinase
inhibitors, synergistic combinations with PARP inhibitors)
• Immune modulation/inflammation as therapy targets
• Mechanisms by which stress hormones affect tumor growth
• Survivorship
• Identify and validate predictors of long-term survival
• Predictors of toxicity

16. • Collaborating organizations:
– M.D. Anderson
– Memorial Sloan Kettering
– Cedars Sinai Medical Center
– Univ. of Iowa
– Univ. of Oklahoma
– OCNA
– Clearity Foundation
– Nine Girls Ask
Consortium to Study Long-Term Survivors of
Ovarian Cancer (DOD)
• Projects:
1. Molecular predictors
2. Biobehavioral, social, and
demographic features
3. Clinical and surgical factors

17. Women’s Cancer Moonshot Team