Clinical IIT Pancreatic Studies

Pancreatic Cancer (ABX266) Andrew Ko / UCSF Phase I Study of Nab-paclitaxel, Gemcitabine & Capecitabine (AGX) in Previously Untreated, Metastatic Pancreatic Cancer Key endpoints: MTD, Safety, TTP, ORR, OS, CA19-9 response Phase I: nab-paclitaxel 100, 125, 150 mg/m2, FDR Gemcitabine 750, 1,000 mg/m2, day 4 every 14 days with Xeloda on days 1-7 750, 1000mg/m2 bid. University of California, San Francisco, Huntsman Cancer Institute Correlates: SPARC n = 36 Phase I in 1st line, untreated pancreatic cancer enroll Nab-paclitaxel, Gemcitabine, Capecitabine 7/7/10: IRB approval for protocol version # 3, dated 4/31/10, contracting almost complete 7/19/10: study activated by Abraxis 7/27/10: study activated at UCSF 7/30/10: 1st patient on study at UCSF 8/11/10: IRB approval at Huntsman Cancer Institute, Dr Kim Jones is PI, contract partially signed on 8/18, waiting for Bruce’s signature 10/15/10: first 3 pts on dose level 0 (100/750/750), accrual on hold until pt 3 completes 3 cycle. 1/28/11: needed to expand dose level 1 due to 2 DLTs, currently have 4 pts on dose level 1, 4th pt on dose level is starting cycle 3, 2 pts from HCI. Study will establish doses for weekly nab-paclitaxel, FDR Gemcitabine and Capecitabine using standard dose escalation schema with 3 to 6 patients per cohort (3+3 design). Will also correlate intratumoral expression of candidate markers mediating sensitivity to chemotherapy to clinical outcomes, including SPARC, DCK, RRM1. CA19-9 biomarker response rate (>50% decline in CA19-9 in patients with >2xULN at baseline). Protocol reviewed during week of 1/25/10 before IRB submission, IND Cross reference letter requested on 1/28, updated IB sent on 1/28/10. Trish emailed Andrew on 2.12.10 that support or SPARC testing withdrawn, Andrew was OK with that decision. Trish reviewed consent, version 1.3, dated 2.12.2010 on 2.16.201 and consent contains needed language. 2nd site at the Huntsman Cancer Institute with Dr Kim Jones, separate contracts with each site. Treatment: until progression or toxicity Status: Active FPI: 7/2010 Enrollment to date: 8 / 3 active Publications to date: None

Pancreatic Cancer (ABX271) Manuel Hidalgo / Centro Integral Oncologico Assessment of Stromal Response to Nab-paclitaxel in combination with gemcitabine in Operable Pancreatic Cancer Primary endpoints: Evaluate the effect on tumor stroma density Evaluate the effect on tumor vessel formation Evaluate the effect of nab-paclitaxel on tumor metabolism Secondary endpoints: Evaluate combination treatment activity in relation with biological changes in tumor stroma and tumor metabolic activity Assess the impact of SPARC expression in tumor and stroma n = 15 Stage I – III Pancreatic cancer Study start delayed (from July 2010 to September 2010) due to limited drug availability in Europe. Nab-paclitaxel 125 mg/m2 weekly Gemcitabine 1000 mg/m2 weekly enroll Status: Active FPI: n/a Enrollment to date: 0 / 0 active Publications to date: none Treatment: 2 cycles Surgery

Pre-clinical Pancreatic Study (ABX273) Manuel Hidalgo / Centro Integral Oncologico Targeting Pancreatic Cancer Stroma Human pancreatic ductal adenocarcinoma xenografts Murine model Aim 1: To determine the effects of combining nab-paclitaxel with other stroma targeting agents hedgehog inhibitors (CUR199691) either alone or in combination with gemcitabine, capecitabine and oxaliplatin Aim 2: To assess the effects of sequential promotion and inhibition of blood vessel formation. It will determine the metastasis promoting effects of anti-stromal drugs as well as the effects of sequential combination of maximal anti-stroma treatments with angiogenesis inhibitors Activated: 10/5/2010 (5% complete) Publications to date: None