1- PROCEEIINGS
`
`V
`
`I EGHT-IETH
`fignuahl‘Meeting of the
`‘ American Associatéon
`for Cancer Rasaarch
`
`a
`
`May 24—27, 1989
`San Franci'sgo, California
`
`
`
`E
`
` \4
`
`Ut Cancrum /
`Vincamus M
`
`lSSN 0197-016X
`
`Phigenix v. Immunogen
`|PR2014-00676
`
`IMMUNOGEN 2309, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`PROCEEDINGS
`
`OF THE
`AMERICAN ASSOCIATION
`FOR CANCER RESEARCH
`
`1
`
`Cancer Research
`Editor
`Peter N. Magee
`
`Managing Editor
`Margaret Foti
`Assistant Managing Editor
`Ma Anne Mennite
`ry
`Senior Stati Editor
`Heide M. Pusztay
`Staii Editors
`Ellen M. McDonald
`Mark G. Hall
`
`Editorial Assistants
`Martha Michael
`‘
`Joseph Helm
`Administrative Secretary
`Margaret A. Plokels
`Editorial Secretaries
`Sandra E. Pettle
`Theresa A. Griffith
`Mary Ellen Pirring
`American Association for
`Cancer Research, inc.
`
`Executive Director
`Margaret Foti
`Senior Administrator
`Adam D. Blisteln
`
`Senior Accountant
`Anthony P. Blenglno
`Financial Assistant
`George L. Moore
`
`Meetings and Development
`Coordinator
`Jeffrey M. Ruben
`Executive Secretaries
`Ruth E. Fortson
`Elizabeth A. Moore
`
`Secretary tor
`Member Services
`Robin E. Felder
`
`
`
`AMERICAN ASSOCIATION FOR CANCER RESEARCH,
`
`INC.
`
`_
`Otilcers
`
`Lawrence A. Loeb, President
`Harris Busch, President-Elect
`Thomas J. King, Treasurer
`Margaret Foti, Executive Director
`
`_
`Board of Directors
`
`Term Expiring May 1989
`
`Margaret L. Kripke
`Brigid G. Leventhal
`Lawrence A. Loeb
`Harold L. Moses
`
`Term Expiring May 1990
`Harris Busch
`Ronald B. Herberman
`Susan B. Horwitz
`John Laszlo
`
`Term Expiring May 1991
`Bernard Fisher
`
`Jay A. Levy
`Sandra R. Wolman
`Stuart H. Yuspa
`
`EX OffiCiO
`Margaret Foti
`Thomas J. King
`Peter N. Magee
`Enrico Mihich
`Alan C. Sartorelli
`
`Address inquiries to the Office of the American Association for Cancer Research, Inc., 530 Walnut Street, 10th Floor, Philadelphia, PA 19106
`(215-440-9300).
`Copyright 1989 by American Association for Cancer Research, lnc. Printed for the American Association for Cancer Research. inc, by Waverly
`Press, inc., Baltimore, MD 21202 and included in subscriptions to the journal Cancer Research. Volume 30 of the Proceedings of the American
`Association for Cancer Research (ISSN 0197-016X) succeeds Volume 29 of the Proceedings of the American Association for Cancer Research. The
`Proceedings may be obtained through registration at the annual meeting of the American Association for Cancer Research, May 24—27, 1989, at a
`price of $20.00. Orders placed directly with the printer are also available at the price of $20.00; bulk discounts are provided upon request.
`' No responsibility is accepted by the Editors, by the American Association for Cancer Research, Inc., or by Waverly Press, inc. for the opinions
`expressed by the contributors or for the contents of the advertisements herein.
`
`IMMUNOGEN 2309. Pg. 2
`Phigenix v. Immunogen
`|PR2014-00676
`
`IMMUNOGEN 2309, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`CLINICAL INVESTIGATIONS
`
`1145
`Interaction of oncof‘etal antigen with malignant melanoma
`pauenty sera.
`F.A. SaHnas, Cancer Control Agency of
`B.C., 600 West
`ions Ave., Vancouver, B.C., V52 4E6,
`Canada.
`.
`We have
`evaluated the reachiUes of
`sera
`from
`maHgnant meMnoma
`(MM) anents upon intmhcfion whh
`Xenogeneic oncofetal
`antigen (XOFA) by using an i_n
`vhro system that annuates tumor burden changes. Each
`serum sample was mixed with XOFA at
`increasing
`concentranns (2 to 20 Hmes). The resuhs demonstrated
`a
`consistent
`inverse
`relationship
`between
`levels
`of
`drCMaHng immune compmxes
`(CIC) and levds of anu-
`XOFA angody (lgG)
`concaflrafion.
`When XOFA-
`containing CIC were
`subjected
`to
`size distribution
`analysis a significant
`relationship was found among CIC
`flze,
`tumor burden and concentrafion of added XOFA.
`Predominant CIC of 10—125 were observed in sera from
`patients with no evidence of disease at sampling time, of
`13-155 in sera from pafients win)
`smaH tumor burden,
`and
`of
`16-185
`in
`sera from patients with advanced
`disease.
`CIC sizes were dependent on the concentrann
`of XOFA and anH-XOFA as we”
`as on
`thMr
`rmafive
`combining reactivlties.
`No increase in baseline levels of
`CIC were observed in parahel analyses of normal or
`non-mahgnant
`control
`sera.
`Our
`resuhs
`iHusuete a
`dynamic interaction of exogenous XOFA, with anti-XOFA
`and CIC present
`in sera from MM patients and suggest
`that analysis of
`size and molecular composition of CIC
`could exlen the changes of CIC concentrafion observed
`in MM patients with different
`tumor burden.
`Such an
`analysis can be clinically relevant
`to disease prognosis.
`The
`study mso
`suggests
`that
`the
`interacfion
`of
`exogenous XOFA and pafienty sera provMe anin vflro
`modeh that shnumtes panents tumor burden changes, K
`study host—tumor interaction.
`
`1146
`R. Amato,
`PHASE 1 CLINICAL EVALUATION OF ELSAMICIN.
`M. Rnber. and L. Schacter.
`The University of Texas
`M. D. Anderson Cancer Center, Houston, Texas
`77030
`Elsamicin is a product of fermentation with a novel
`chemical structure that is not related to other known
`chemotherapeutic agents.
`Its mechanism of action is un—
`known.
`In preclinical studies it is active against the
`mnrine tumors 9388, L1210, 316, M5076, as well as the nxl
`and HGT—116 xenografts using the subrenal capsule assay.
`It is active against a variety of human tumor cell lines
`independent of route or schedule of administration.
`The
`mouse LDlO is 50 mgs/m2 as a single injection.
`In dogs,
`3.12 mgs/m2 (5% MELDlO) was uniformly lethal, while 1.8
`mgs/m2 was well tolerated.
`
`We are conducting a phase I clinical evaluation of
`Eisamicln given as an intravenous bolus every three weeks.
`The starting dose was 0.6 mga/m2 (1/3 of the TDL in dogs).
`To date, 16 patients with metastatic solid tumors re~
`firaclory to standard therapy (9 female/7 male, median
`performance status 1, median age 59, prior chemotherapy
`15, prior immune therapy 4, prior radiation therapy 11),
`have received 22 courses;
`To date six dose escalations
`have been achieved,
`(0.6, 1.2, 2.4, 4.8, 712, and 10.8
`mgs/mz). One patient at 4.8 mgs/m2 developed grade II
`leukopenia associated with a grade I thrombocytopenia.
`One other patient developed a grade I thrombocytopenia at
`7.2 mgs/mz.
`No other patients have experienced myelo—
`suppression. Nonhematologic toxicity has been minimal.
`The study is ongoing.
`
`1147
`TREATMENT OF ADVANCED METASTATIC MELANOMA USING
`SINGLE DOSE MURINE MONOCLONAL ANTIBODY - RICIN A
`CHAIN IMMUNOTOXIN WITH DOSE ESCALATION — A PHASE
`I STUDY. P. Salem, A. Zukiwski, w. Robinson, P.
`Bunn, R. Lamb, R.s. Benjamin, L. Spitler, N.
`Wedel, and S. Ackerman. The U.T. M.D. Anderson
`Cancer Center
`(MDACC), Houston, TX, The Univer—
`sity of Colorado Medical Ctr., Denver, CO, and
`XOMA Corp., Berkeley, CA.
`A phase I study utilizing single dose murine
`monoclonal anti—melanoma antibody — Rioin A chain
`immunotoxin (XOMAZYME—MEL)
`in the treatment of
`advanced malignant melanoma was jointly conducted
`at MDACC and the University of Colorado Medical
`Center. A total of 19 patients (pts) were
`treated. The immunotoxin was given as an infusion
`over 30 min. and in all pts except one,
`a single
`infusion was given. The starting dose was 0.6
`mg/kg and was escalated stepwise by 25% to a
`maximum of 1.6 mg/kg. Six pts were treated at 1.6
`mg/kg dose level and four of them developed grade
`I
`Iv fatigue (reduction in pt's activity to < 25%)
`and grade III myalgias (requiring narcotics).
`These toxicities were considered limiting. They
`were first noted 4 days after drug administra—
`tion and they lasted approximately 1 week. Other
`non—limiting toxicities were: mild hypotension,
`decrease in serum albumin associated with weight
`gain and peripheral edema, and flu—like syndrome.
`The severity of these toxicities was also dose
`dependent. All pts were considered evaluable for
`response. There was one PR and one minor respon—
`se.
`In conclusion,
`the maximum tolerated dose of
`XOMAZYME—MEL, when given as a single infusion of
`30 minutes is 1.6 mg/kg.
`
`1148
`IN ADULTS; AN OVER
`SKELETAL EWING'S SARCOMA (ES)
`40 YEARS' EXPERIENCE. N.E.J. Papadopoulos, R.S.
`Benjamin, C. Plager, A. Ayala, M. Romsdahl and
`John Murray. The University of Texas M.D. Anderson
`Cancer Center, Houston, Texas 77030.
`One hundred ten adult
`(age 2 16) patients
`(pts) with-ES and no metastases at diagnosis were
`retrospectively reviewed. There were 72 males and
`38 females. Primary location included long bones
`(51), pelvis (25), spinei(8), ribsl(1l), clavicle
`(2), skull
`(2), scapula (7),
`foot
`(4). The 5—year
`survival
`(5Y8) of all pts was 36%. Those who
`received primary treatment with chemotherapy that
`included adriamycin (A) did the best: CMVADIC 48%
`and CAV 35%. For pts with extremity lesions,
`the
`most favorable site (47% 5Y5), and A chemotherapy,
`those treated with surgery had a 73% SYS compared
`with 48% for those without surgery (p=0.10)
`whereas those treated with radiation (54% 5Y8) did
`no better than those treated without radiation
`(65% SYS)
`(p=0.2). Thirteen pts had resection of
`the primary lesion after treatment with
`chemotherapy only. Ten pts with microscopic or no
`residual tumor had DFS of 90%.
`In contrast, 3 pts
`with residual tumor 2 10% all died (p=0.004).
`In
`conclusion: a) Chemotherapy should be the primary
`treatment Eor ES. b) Primary lesions should be
`resected if feasible. c) Degree of tumor necrosis
`after primary chemotherapy becomes an important
`prognostic factor. d) The adjuctive role of radia—
`tion therapy in the primary treatment of ES is
`questionable.
`
`PROCEEDINGS OF THEAMERICAN ASSOCIATION FOR CANCER RESEARCH
`VOLUME 30 0 MARCH 1989
`288
`
`
`
`IMMUNOGEN 2309, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
`
`