Sandoz Inc. IPR2016-00318
`Sandoz v. Eli Lilly, Exhibit 1070-0001
`
`

`
`Program/Proceedings
`of the
`$tmerican Society of Clinical Oncology
`
`Michael C. Perry, MD
`Program/Proceedings Editor
`
`American Society of Clinical Oncology
`
`Officers
`
`1997.98
`
`Robert J. Mayer, MD
`
`Allen S, Lichtar, MD
`President-Elect
`James O. Armitage, lVID
`Immediate Past President
`
`William P. Vaughan, MD
`Secretary/Treasurer
`
`Board of Directors
`Douglas W. Blayne:~ MD
`George J. Bosl, MD
`PaulA. Bunn, Jr., MD
`Nancy E. Davidson, MD
`Jay R. Harris, MD
`Harry E. Hynes, MD, PhD
`John D. Minna, MD
`Larry Norton, MD
`Philip A. Pizzo, MD
`James Lloyd Wade III, MD
`Barbara Lynn Weber, M:D
`William C. Wood, MD
`
`John R. Durant, MD
`Executive Vice President
`
`Al~txact management and indexing prodded by Prism Productions, Inc., Westervflle, OH
`
`Electronic page ~npositiau a~d print productionpmvided by W.B. Saunde.~ Company, Philadelphia,
`and the Mack Printing Group.
`
`0. (~opyri~t 1998 by the American Society of Cliai~ On~logy
`
`Sandoz Inc. IPR2016-00318
`Sandoz v. Eli Lilly, Exhibit 1070-0002
`
`

`
`Proceedings of ASCO Volume 171998
`
`GENITOURINARY CANCER
`
`339a
`
`1305
`ADJUVANT AOMINISTRATION OF SUBCUTANEOUS (SC) IN1TRLEUKIN-2 (RIL-2)
`IN PATIENTS FOLLOWING RESECTION OF RENAL CELL CARCINOMA: PREMMI-
`N~RY RESULT~ OF A PILOTSTUDY. T. Olencki, R.M. Bukowski, K. Zuccaro, D.
`McLain, P. Elson, J. Finke, A. Novick. Cleveland Clinic Foundation,
`Cleveland, OH.
`Adjuvant administration of rlL-2 following resection of locally advanced
`(T~-c Nz Mo) or metastatic renal cell carcinoma was investigated to
`determine toxicity and patient (pt) tolerance to 4 different SC rlL-2
`regimens. Pts with adequate cardiovascular, renal and hepatic function
`who had no evidence of residual disease were treated within 3 mos of
`surgery. Pts. were randomized to receive rlL-2 at either 2.0 or 4.0 MIU/m2
`S.C. BID dl-5 q o wk (cohorts I & II respectively) or wks 1-4 every 8 wks
`(cohorts III & IV respectively) for a total of 24 wks. Dose reduction (50%)
`for ~ Gr III toxicity or patient intolerance was permitted. 24 pts (6/cohort)
`will be entered, with 17 entered to date (stage 111-15, stage IV-2). 15 pts
`are currently evalual31e and preliminary results are as follows:
`
`Cohort
`
`No. Eval.
`
`Completed
`24 wks
`
`Dose
`Reduction
`
`Currently
`On Therapy
`
`I
`II
`III
`IV
`
`414
`4/4
`5/4
`4/3
`
`2
`2
`2
`1
`
`0
`0
`1
`1
`
`1
`1
`1
`2
`
`Toxicity included constitutional symptoms in all pts and Gr III hepatic
`toxicity consisting of SGOT elevation (1 pt cohort IV) which subsequently
`returned to normal. Dose reduction or discontinuation of rlL-2 was required
`in 2/15 (pt request) and 1/15 patients respectively, with no major
`differences between the cohorts apparent. Progressive disease developed
`in 4/15 pts. Prolonged S.C. administration of rlL-2 is possible, in an
`adjuvant setting, and early discontinuation because of pt intolerance or
`toxicity does not appear excessive. It remains unclear which regimen is
`optimal in terms of patient compliance/tolerance. Adjuvant trials compar-
`ing rlL-2 to surgery alone in high risk renal cell carcinoma patients should
`be performed (supported by Chiton Therapeutics).
`
`1307
`A PHASE II STUDY OF THE MULTI-TARgETED ANTIFOLATE, MTA (LY231514), IN
`PATIENTS WITH ADVANCED TRANSITIONAL CELL CARCINOMA (TCC) OF THE
`BLADDER. L. Paz.Ares, J. Tabemero, A. Moya~o, J. Rifa, H. Gomez, E.
`Marcuello, A. Gonzalez, I. Tarazona, H. Cort~s-Funes, H. Dote de Octubre,
`Madrid, Spain; H. Sant Pau, Barcelona, Spain; H. R y Cajal Madrid, Spain;
`H. Son Dureta, Palma de Mallorca, Spain; Lilly Spain.
`MTA is a novel multi-targeted antifolate that inhibits multiple folate-
`dependent enzymes, including thymidylata synthase (TS), dihydrofolate
`reductase (DHFR) and glycinamJde ribonucleotide formyltransferase
`(GARFT). MTA has activity in preclinical models and human tumors (breast,
`colon and lung). We undertook a phase II trial of MTA in 22 patients (pts)
`with advanced TCC of the bladder. MTA was administered as 10 minute
`infusions every 3 weeks, ata dose of 600 mWm2 (first 6 pts) or 500 mg/m2
`(subsequent pts). 18 pts are currently evaluable. 1 was ineligible (prior
`chemotherapy), 3 are too early. Median age was 66 years (range: 48-76);
`17 were male; PS was 0 (6 pta), I (10 pts) and 2 (2 pts). All ts had
`metastatic disease; median number of disease sites: 2 (range: 1-4). 60
`courses were administered, median cycleeipt: 3 (range 1-12). Five courses
`(8%) were dose-reduced and 6 (10%) delayed. The main toxicity was
`hematologic: 8 pts (44%) had grade (G) 3 and 5 pts (28%) G4 neutropenia;
`4 pts developed neutropenic fever; 1 pt had G3 thrombocytopenia; 3 pts
`G2-4 anemia. Non-hematologic toxicity included: skin rash (G1/2:10 pts,
`G3:1 pt) preventable with dexamethasone, nausea/uomitin8 (G1/2:)0
`pts), stomatitis (G1/2:7 pts, G3:1 pt), diarrhea (G3:2 pts), and alopecia
`(G 1: 3 pts). There were 2 toxic deaths (septicemia and renal failure). Doses
`were subsequently reduced to 500 mg/mz due to toxicity. Six pts (33%,
`95% Ch 13-59%) had a partial remission, 4 (22%) had stable disease, 7
`(39%) had progressive disease (1 pt died after the first course--reported
`above as the toxic death due to septicemia). Responses lasted for 1.5+ to 8
`months. In conclusion, MTA has definitive antitumor activity in advanced
`TCC of the bladder, but its toxicity is significant.
`
`1306
`BLADDER PRESERVATION IN LOCALLY ADVANCED (T2-T4) TRANSITIONAL BLAD-
`DER CARCINOMA (TgC) AFTER TRANSURETHRAL RESECTION (I’UR) AND NEOAD-
`JUVANT CHEMDRADIOTHERAPY. R. Passalacqua, N. Naldi, F. Leonardi, G.
`Ceci, V Franciosi, L. Bidin, V. Paietta, B. Monica, A. Prati, D. Potenzoni, G.
`Sanfilippo, M. Fuma~alli, R. Martinelli, R. Camisa, G. CocconL Medical
`Oncolo~y, Urology Division and Radiotherapy, Azienda Ospedaliera, Urolog~
`Division, Azienda USL, Parma, Italy.
`This is a single institution study aiming to evaluate, in muscle invasive BC,
`an approach of TUR, chemotherapy and pelvic radiotherapy (RT) in terms of
`bladder preservation, survival and toxicity. Since March 1994, 55 T2-T4
`NO-N 1, MO patients (pts) entered the study. Median age was 65 (42-77);
`T2-T3a: 36%; T3b: 49%, T4: 13%, G3: 89%, M/F ratio: 4916, PS
`100-90: 76%, 80-60: 24%. All pts underwent an initial TUR and were
`treated w=th cispiatin (P) 20 mg/m2 and 5-Fluorouracil (F) 200 mg/mz daily
`for 5 days on weeks 1,4 and 7. Pelvic RT (2 Gy/die for 5 days each week)
`was delivered on weeks 2-3 and 5-6 for a total of 40 Gy in 4 weeks. Pts
`were then evaluated with cystoscopy, multiple biopsies, CT scan and urine
`cytology. Pts with residual disease were considered as incomplete respond-
`ers (IR) and an immediate cystectomy was proposed. Complete responders
`(CR) were treated with 2 additional PF cycles plus a further bladder RT
`boost with 24-28 Gy. At present 53 pts are evaluable for response; 38
`(72%) achieved a complete histological response (89% for T2-T3a, 74%
`for T3b, 14% for T4). 15 were IR and 12 accepted an immediate
`cystectomy. With a median follow-up of 15 months (2-44), 5/15 (33%) in
`the IR group relapsed and died for distant metastasis; in the RC graup 9/38
`(24%) relapsed (6 in the bladder and 3 in distant sites) and 2/38 (5%)
`died. Toxicity was mild: neutropenia gr. 3-4: 23%; diarrhea gr. 2-3: 27%,
`cystitis gr. 3: 4%. Conclusions: this combined approach of TUR and
`alternated chemoradiotherapy induces an high rate of CR, is well tolerated
`even in the elderly pts, and represents a valid treatment for locally
`advanced TBC in a therapeutical conservative perspective.
`
`1308
`A PHASE II TRIAL OF LIPOSOMAL DOXORBICIN (DOXILe) IN THE TREATMENT OF
`ADVANCED RENAL CELL CANCER: A HOOSIER ONCOLUSY GROUP (HOG) STUDY.
`K. Pennington, M. Gordon, J. Picus. Hoosier Oncology Group and the
`Walther Cancer Institute, Indianapolis, IN.
`Metastatic renal cell cancer has few effective therapies. Standard chemo-
`therapy has poor response rates and minimal impact on survival. Early
`responses in phase I trials of Doxil® in patients with advanced renal cell
`cancer prompted the HOG to conduct a formal phase II trial. Between
`7/10/96 and 1U7197 a total of 32 patients was entered onto this trial.
`Eligibility criteria included biopsy proven renal cell cancer that was
`metastatic or unresectable, KPS > 60%, no prior chemotherapy, ~1 prior
`immunotherapy regimen, Creatinine -=2.5, and no clinical evidence of
`compromised cardiac function. Patients received 50 mg/mz IV every 28
`days. Standard dose reductions for cytopenia were employed, along with
`dose reductions for plantar-palmar erythema. The patients ranged in age
`from 38-78 years (median 60) with a median KPS of 90. Twelve patients
`had previous immunotherapy. A maximum of eight cycles was allowed, and
`five patients received that number of cycles. The median number of cycles
`was three. One patient showed a partial response based on standard
`criteria, which lasted 190 days. Thirteen additional patients showed stable
`disease, that lasted a median of 105 days. Fourteen patients showed
`progressive disease, without evidence of disease stabilization. The median
`survival is 10 months, with 19 patients still alive. Major grade III or IV
`toxicities included fatigue (4), leukopenia (3), skin or hand-foot Syndrome
`(3), stomatitis or mucositis (2), constipation (2), infection (1], nausea or
`vomiting (I). More minor nausea (grade I or II} was seen in 6 other patients.
`Only 2 patients had grade I and I patient had grade II cardiotoxicity. This
`regimen was very well tolerated, but unfortunately only exhibited minimal
`evidence of tumor response.
`Supported by Sequus Pharmaceuticals, Inc.
`
`Sandoz Inc. IPR2016-00318
`Sandoz v. Eli Lilly, Exhibit 1070-0003