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

Concept: Make the Impossible…Possible

John F. Kennedy Moon Speech, Rice Stadium September 12, 1962

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?

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

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

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

Goal: 80% decrease in deaths in

family members over 5 years

Flagship project 1a: Impacting the Family

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

Flagship Project 2: Personalizing Surgical Therapy

Impact of residual disease: Overall survival

Dubois et al, Cancer, 2009: Mar 15; 115(6): 1234-44

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

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%

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

NEW MOONSHOT PROJECTS-FP2B OVARIAN Fl

agsh

ip P

roje

ct 2

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

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

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

• 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

Women’s Cancer Moonshot Team