Trans-Arterial Chemotherapy for Treatment of Locally Advanced - - PowerPoint PPT Presentation

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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

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

Disclosures

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• 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 System Trans-Arterial Micro-Perfusion (TAMP) isolates the anatomy and micro-perfuses targeted tissue with (Intra-Arterial gemcitabine)

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

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Mechanism: pressure mediated Trans-Arterial Micro-Perfusion (TAMP) Gemcitabine distribution

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10 20 30 40 50 60 70

Pressure (mmHG)

Catheter in artery

First balloon up Second balloon up Start infusion

At ~45mmHg - tissue pressure is

• vercome, forcing

chemotherapy out

• f vessel

99%

Permeating through arterial wall into tissue

1%

Remaining in arterial wall Proxim al balloon Distal balloon

At ~45mmHg - tissue pressure is

• vercome, forcing

chemotherapy out

• f 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 Months

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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5 10 15 20 25 30 35 Months

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

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2 4 6 8 10 12 Months

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

• utflow 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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