RENOVO RX Delivering therapy where it mattersRENOVO RX Delivering therapy where it matters

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Trans-Arterial Chemotherapy for Treatment of Locally Advanced Pancreatic Cancer: Treatment Factors Impacting Survival

H. Charles Li – RenovoRx

Alex S. Tsobanoudis, Jiali Li, Alexander Rosemurgy, J. Augusto Bastidas,

Emmanuel Zervos, Steven Goldin, Peter Muscarella II, Charles Nutting, Barish

Edil, Reza Malek, Ramtin Agah

RENOVO RX Delivering therapy where it matters

• This study was funded by RenovoRx (Los Altos, CA)

Disclosures

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RENOVO RX Delivering therapy where it matters

• By the end of 2020, pancreatic cancer is expected to be 2nd most deadly cancer

• While surgical resection is the best course, due to location of pancreas, tumors in the pancreas are hard to detect until locally advanced and unresectable

• Current standard treatment for locally advanced unresectable pancreatic cancer is systemic chemo

• Pancreatic tumors are avascular and surrounded by dense matrix, hence systemic chemo not efficacious

• Median OS is generally 12 to 15 months

LAPC Background and Current Treatments

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• Trans-Arterial Micro Perfusion (TAMP) is a new technique being used to deliver gemcitabine locally to pancreatic adenocarcinoma in patients that are not candidates for curative resection

• The technique involves occluding the vessel adjacent to the tumor, using a dual balloon catheter, then infusing the drug between the balloons to create a pressure gradient resulting in diffusion of the drug across the arterial wall into the surrounding tissue – including the tumor

LAPC Background and Current Treatments

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RenovoRx is developing therapies for localized treatment of solid cancer tumors to Increase Survival & Improve Quality of Life

The RenovoCathTM SystemTrans-Arterial Micro-Perfusion (TAMP) isolates the anatomy and micro-perfuses targeted tissue with (Intra-Arterial gemcitabine)

RX

Targeted localized therapy where Standard of Care systemic chemotherapy can’t reach

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Mechanism: pressure mediated Trans-ArterialMicro-Perfusion (TAMP)

Gemcitabine distribution

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0

10

20

30

40

50

60

70

Pre

ssu

re (

mm

HG

)

Catheter in artery

First balloon up Second

balloon up

Start infusion

At ~45mmHg -tissue pressure is overcome, forcing chemotherapy out

of vessel

99%Permeating through

arterial wall into tissue

1%Remaining in

arterial wall

Proximal

balloon

Distal balloon

At ~45mmHg -tissue pressure is overcome, forcing chemotherapy out

of vessel

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• Eight US sites enrolled 43 patients receiving over 190 total IA treatments using RenovoCath, as part of a Phase I/II safety and follow-up registry studies. Nineteen patients were treatment naïve, 11 patients had prior chemotherapy, and 12 had prior chemoradiation, with 1 patient having had prior whipple procedure.

• Treatment involved isolating portion of artery abutting pancreatic tumor and infusing gemcitabine over 20 minutes.

• Most received full dose (1000mg/m2) and was well tolerated

• Treatment arteries included SMA, celiac, common hepatic, and splenic, or a combination

Methods

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• We analyzed these data in 43 patients in 2 studies that received up to 190 TAMP treatments

• The following variables showed correlation for improved survival in multivariate analysis:

• Prior treatment (radiation, chemotherapy, or treatment naïve)

• Location of treatment

• Number of treatments

Methods

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Results – Prior Treatment

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5

10

15

20

25

30

Mo

nth

s

Prior Treatment on Median OS

Radiation (n=12) Chemo Only (n=11) Tx Naïve (n=19)

p < 0.01

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Results – Treatment Location

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0

5

10

15

20

25

30

35M

on

ths

Treatment Location on Median OS

SMA (n=13) Non-SMA (n=17) Mixed (SMA+Others) (n=13)

p < 0.01

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Results – Number of Treatments

11

0

2

4

6

8

10

12M

on

ths

Number of Treatments on Survival (from 1st Tx)

1-5 Tx (n=27) 6 or more Tx (n=16)

p < 0.05

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• Intra-arterial gemcitabine/TAMP is safe and efficacious

• Increased number of treatment shows greater survival benefits

• Patients had varying number of treatments, ranging from 1 to 14

• Patients receiving radiotherapy prior to direct, intra-arterial gemcitabine infusion were shown to have better survival than patients receiving prior systemic chemo or no prior treatments.

• Radiation damages and eliminates microvasculature around the tumor, allowing targeted, local chemotherapy to more directly reach the tumor, as opposed to washing out in the vasculature.

Summary/Conclusion

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Mechanism : Trans-Arterial Micro-Perfusion (TAMP)

combined with radiation

Native vasculature and IA chemo lead to Micro-vascular washout

Irradiated vasculature and IA chemo lead to Diffusion

Radiation reduces venous outflow by decreasing the microvasculature

Distal RenovoCath™

balloon

Microvascular

washout

Proximal

RenovoCathTM balloon

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• Using the RenovoCath via the SMA showed increased benefit compared to treatment in other arteries.

• Despite avascular tumor, the SMA is the largest and closest artery supplying the pancreas.

Summary/Conclusion

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SMA is surrounded by pancreatic tissue = better tissue penetration

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• Current Phase III trial on-going to compare intra-arterial gemcitabine (TAMP) vs. SOC gemcitabine and nab-paclitaxel (systemic IV)

Summary/Conclusion

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