`
`IMMUNOGEN 2293, Pg. 1
`Phigenix v. Immunogen
`|PR2014-00676
`
`IMMUNOGEN 2293, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`Program/ Proceedings of the
`American Society of Clinical Oncology
`
`
`AMERICAN SOCIETY OF CLINICAL ONCOLOGY, INC.
`
`OFFICERS
`
`1989—1990
`
`President, Robert C. Young
`
`Rresident-Elect, Harvey M. Golomb
`
`Immediate Past President, Charles A. Coliman, Jr.
`
`Secretary-Treasurer, John W. Yarbro
`
`BOARD OF DIRECTORS
`
`Karen Antman
`James O. Armitage
`John H. Glick
`
`Stephen E. Jones
`Robert J. Mayer
`Gary A. Presant
`James B. Gantenberg
`Executive Director
`
`‘
`
`
`
`Brigid Leventhal, Editor
`
`Editorial Staff provided by W.B. Saunders Company.
`
`
`Copyright 1990 by the American Society of Clinical Oncology.
`
`IMMUNOGEN 2293, Pg. 2
`Phigenix v. Immunogen
`|PR2014-00676
`
`IMMUNOGEN 2293, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`IMMUNOLOGY AND CYTOKINES
`
`'721
`TREATMENT OF T CELL LYMPHOMA WITH MONOCLONAL ANTI-
`IDIOTYPE ANTIBODY. D.G. Maloney, H.T. Maecker. S. Takahashi,
`D. Czerwinskl and Ft. Levy. Stanford Medical Center, Slanlord
`CA 94305.
`Epitopes formed by the combination of the alpha and beta
`chains of
`the T cell antigen receptor provide a clonotypio
`marker for monoclonal tumors of T cell origin. We report here
`the production and therapeutic use pi a monoclonal anti-
`ldiotype antibody against the T cell receptor of a patient with
`cutaneous T cell lymphoma. Balb/c mice were immunized with
`tumor Cells and hybrldomas screened for
`the ability to co-
`modulate 003 then further selected for
`tumor specificity by
`cell staining and immunopreclpitation. HLl precipitatedthe
`alpha and beta chains of the T cell receptor but not
`the CD3
`complex from tumor cells.
`it bound to patient tumor cells. but
`not to other cloned T cell lines and less that 4 percent of cells in
`tonsil or blood.
`In
`vitro. HLt had no eitect on the
`incorporation ct SH-thymidine.
`Rapidly increasing skin
`lesions occurred following discontinuation otchemolherapy
`prior
`to antibody treatments.
`The patient was treated with
`antibody given IV three times each week for two.
`three week
`courses. The dose was escalated to 300 mg to obtain Circulating
`antibody. Blood and skin tumor cells were rapidly coated with
`antibody. Serum samples were monitored for antibody level
`and circulating tumor cells analyzed by FACS. Skin biopsies
`documented a reduction in tumor burden. HLi positive cells
`remained in the blood despite being coated with antibody. The
`patient had initial worsening then clearing of his skin lesions
`over the lollowlng four months. We conclude.
`that
`like antl-
`idiolype therapy of B cell malignancies. anti-idlotypio T cell
`antibodies hold promise as anti-tumor
`immunolherapeulic
`agents.
`
`'722
`ANTIvTRANSFERRIN RECEPTOR IMMUNOTOXIN (IT) THERAPY: PHASE-l
`[NTRAPERITONEAL (i.p.) TRIAL. M.A. Bookman, S. Godfrey, K. Pndnvic. T.
`Griffin. LP. Cordn. T. Hamilton, R.F. 02.015, 13.3. Groves. Fox Chase Cancer
`Center (FCCC), Philnladolphia, PA 19111; U. Muss. Medical School. Worcester.
`MA 01605; and Cetus Corp., Emeryville, CA 94608.
`The transferrin receptor (TfR) is uniformly expressed on malignant. as well.
`as normnl cells,
`is efficiently intomnlizcd. and is a suitable target for IT delivery.
`The mnrina nnti-TfR monoclonnl antibody 454Al2. was linked via a reducible disulfido
`bond to recombinant ricin A-chnin (rRA. Cetus) to create 454A12-rRA. Efficacy was
`demonstrated in preclinical studios using a xenogeneic nude mouse model with human
`ovarian cancer (FitzGerald. et al. Cancer Res 47: 1407. 1987) Mid n syngencic murine
`model with different nnti-TfR lTs (Bjorn and Gmetsemn, Cancer Res 47:6§39. I987).
`A clinical trial was initiated for patients (pts) with ovarian, mesothelinl. renal, and
`gastrointestinal cancer involving the peritoneal cavity:
`Target Doses:
`20 pg test dose day i; then 5, 10. 25, 50, 100 nglkg daily x 5
`days !.p, in 2000 ml dialysnte (1.5% dextrose)
`Accmnl (11/89):
`10 pts treated at FCCC and U. Moss, Medical School
`Maximum Done:
`20 pg test does followed by 25 rig/kg x 5 doses
`Toxicity:
`IT-rclated: Hypoalbuminomin Grl (all pts) and malaise.
`Not clearly IT-related: Poritonitis (1 pt,
`1 dose) and partial
`bowel obstmction (1 pt,
`1 dose). No myelosupprcssiou.
`mucositis, skin rush, or neurologic toxicity.
`Intact IT measured by sandwich ELISA (3 pts @ 5 [lg/kg).
`Lp. levels sustained in 3 pts between 20 and 150 ng/ml x 5 days.
`Serum levels detectable in 1 pt between 3 and 10 ng/ml.
`0 CR. 0 PR.
`I decreased ascites. 5 progressive disease.
`Response:
`Untreated nscites tumors were evaluated for Tilt by immunohistochomicnl staining and
`immunofluorescent staining with flow cytometry.
`IT-rnediated protein synthesis
`inhibition (Icso) was measured by [3H]-leucine incorporation @24 hrs. All tumors
`examined were TtR(+) and lle ICSO values between 10 and 100 ng/ml. Data
`regarding formation of neutralizing antibodies are pending. We conclude that anti~
`Tl‘R IT can be administered Lp. with acceptable toxicity to pts with cancer at doses
`Which achieve detectable serum levels and with i.p. levels that exceed the in Vitro
`le. Dose escalation continues on this study to determine the spectrum of dose-
`limiting toxicity and obtain additional biological data.
`
`IT Levels:
`
`'723
`A PHASE II STUDY OF DACARBAZlNE (DTIC), CISPLRTIN (DDP),
`AND OUTPATIENT INTERLEUKlN-e (IL—a)
`(RIDD-al
`1N METASTATIC
`MALIGNANT MELRNOMA (M.M.M.l.
`L. Flaherty, N. Robinson,
`8. Redman, R. Gonzales. 5. Martina,
`t1. Kraut,
`H. Valdivieso, and A. Rudolph. Wayne State Univ.,
`,Detroit, "1., 48201, Univ. of Colorado, Denver,
`(30.,
`80220, and Cetus Corp., Emeryville, CA., 94608.
`The tolerablllty of DTIC and outpatient
`lL—E along
`with a median survival of 8.5 mos., and responses in
`visceral organs (ASCO, 7:854, 1988)
`in MM”, prompted the
`present ongoing phase ll study of DTIC, DDP, and lL-E.
`DTIC (750 mg/M”)
`IV over 30 min. and DDP (100 mg/M”)
`IV
`over 30 min. are administered on Day 1.
`lL-a 29.0 x 10*
`lU/Ma IV bolus is administered die-to, d19—23 of each 28
`day cycle.
`25 patients (pts.) have been registered to
`date and 91 cycles of therapy have been evaluated for
`toxicity. Patient characteristics include median age—SE
`y.o.
`(16-74), males 13, females 13, performance status 0-1
`in at pta., a 1n 4 pts.
`No pt. had prior chemotherapy.
`17 pts. had visceral
`involvement. Toxicity consisting
`primarily of fatigue, anorexia, arthralgies, vomiting,
`fever and chills, necessitated 13 lL—E dose reductions.
`The mean dose of lL-a administered has been 81.3 x 10°
`IU/ME. Renal
`toxicity lcreatlnlna clearance (coco/min.)
`has occurred in 11/91 courses.
`E4 pts. are evaluable for
`response with E CR‘o and 7 PR’s (38% RR).
`E pta. have
`been rendered disease—free with additional surgery. CR's
`have occurred in soft tissue and lymph nodes.
`PR's have
`occurred in soft tissue,
`lymph node,
`lung,
`liver, spleen,
`and adrenals.
`DTIC and DDP did not interfere with the
`repeated generation of NK and LAK activity. This program
`has been tolerable and more effective than our prior
`efforts combining DTIC and lL-E.
`lL-E was provided by Cetus Corp., Emeryvilla, CA.
`
`’
`'724
`IN‘I'ERLEUKIN 2 (1L2) +
`HUMAN
`RECOMBINANT
`+
`ALPHA—INTERFKRON
`( LAK)
`LYMPHOCYTES
`METASTATIC RENAL CELL CARCINOMA.
`
`ILZ ACTIVATE)
`( ot-IFN)
`IN
`
`G.
`stoter‘, S.H. Goey‘
`t C.J.A. Punt“, cm. Pranks’. c.
`barriers1 , R.L.I-t. Bolhuls .
`l) Rotterdam Cancer: Institute,
`Rotterdam. The Netherlands 2) EuroCelzus BV, Amsterdam,
`The Netherlands
`3) University Hospital, Nljniegen, The
`Netherlands
`.
`-
`
`Sixteen patients (pt-.5) with measurable metastatic renal
`cell
`carcinoma
`have been treated with daily continuous
`intravenous
`(c.i.v.)
`infusion of
`ILZ 18 MIU/inz/day,
`(1
`1—5.
`Leukapheresis is performed at: d 7~9.
`LAX is given
`following leukapheresis
`at:
`d
`12—14 with 1L2 d 12—16.
`oc—IFN 5 MU/‘mz/day 1.m. is given at: it 12—15. This cycle is
`repeated at: day
`36.
`Patients with stable disease or
`response
`receive 4 maintenance cycles consisting of
`IL2
`18 MIU/mz/day c.i..v., at 1—4 and u—IFN 5 MU/mz/day 1.m.
`d
`1—4.
`Cycles are repeated every 4 weeks. There were
`11
`males and 5 females with a median age of 52 (39~65) and a
`Karnofsky
`index of
`100
`(80—100). All patients had
`undergone nephrectomy of
`the primary tumor. Metastatic
`sites were lung, pleura,
`lymph nodes, liver, mesentery,
`and retroperitoneum. Among 12 evaluable pts, we observed
`4 (33%) Emulate
`responses
`(CR),
`and 3 pts have stable
`disease while still on therapy. All responses occurred in
`lung and pleural metastases.
`one
`CR relapsed after: 5
`are
`months. The remaining 3 CR5
`lasting 4", 8+ and 11"
`months.
`side effects were similar to those expected from
`each treatment: component:
`alone.
`one patient developed a
`fatal myocardial infarction between cycle 1 and 2 with a
`ventricular septum defect.
`These preliminary results
`show
`a high CR
`rate as
`compared
`to our previous
`experience with 1L2 alone and 11.2 + LAK.
`N.B.: 1 Cetus Unit «a 6 International Units (IU)
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`PROCEEDINGS OF ASCO VOL. 9 MARCH 1990
`187
`
`
`
`IMMUNOGEN 2293, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
`
`