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SARC011/NO21157. Alberto Pappo, M.D. Texas Children’s Cancer Center Houston, TX. SARC011/NO21157.

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Sarc011 no21157

SARC011/NO21157

Alberto Pappo, M.D.

Texas Children’s Cancer Center

Houston, TX


Sarc011 no211571

SARC011/NO21157

SARC Global Collaboration: A Phase II trial of R1507, a recombinant human monoclonal antibody to the insulin-like growth factor-1 receptor for the treatment of patients with recurrent or refractory Ewing’s sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas

2

2


R1507 shows anti tumor activity in the clinic phase i

Pt. 8012

Baseline

Dec 8, 2006

Restaging Week 6

Jan 25, 2007

R1507 shows anti-tumor activity in the clinic- Phase I

Pt. 7002

  • Patient 7002:

  • 27yo male

  • Ewing’s sarcoma of chest wall with lung metastasis (1997)

  • SD → Partial Response after 25 weeks of R1507 at 1 mg/kg/week.

Baseline

June 19, 2006

Restaging Week 25

Dec 29, 2006

  • Patient 8012:

  • 28yo female

  • Ewing’s sarcoma of sacrum with lung metastasis (2003)

  • PR after 6 weeks of R1507 at 9 mg/kg/week


Sarc011 no21157

Determine the ORR to R1507 in pts with recurrent or refractory Ewing sarcoma (secondary cohort) osteosarcoma, synovial sarcoma, rhabdomyosarcoma, and other sarcomas: ASPS, CCS, EMS, DSRCT, MLS

Determine PFS at 18 wks for patients treated with R1507 with progressive, recurrent or refractory ESFT (primary cohort)

SARC011/NO21157 Primary Objectives


Sarc 011 secondary objectives

SARC 011Secondary Objectives

  • Determine duration of response, PFS at 18 wks and overall PFS for pts with recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma, and other sarcomas-ASPS, CCS, EMS,DSRCT, MLS.

  • Determine ORR, response duration, overall PFS in patients with Ewing sarcoma

  • PK,Tolerability and AE profile of R 1507


Sarc011 no21157

PET scan changes

Serum Biomarkers

SARC011/NO21157 Exploratory Objectives


Protocol amendment v3 8 1 08

Protocol Amendment v3 8-1-08

  • Reduced the age from ≥ 12 to ≥ 2 years

  • Expanded “others” cohort to 10 patients for each subtype, then if 1PR an additional 10 patients

    • Alveolar Soft Part Sarcoma

    • Clear Cell Sarcoma

    • Extraskeletal Myxoid Chondrosarcoma

    • Desmoplastic Round Cell Tumor

    • Myxoid Liposarcoma


Sarc011 no21157 statistical considerations

SARC011/NO21157 Statistical Considerations

  • Ewing’s Primary cohort

    • Relapse ≤ 24 months AND at least 2 previous chemo regimen, surgically unresectable

    • 65 patients

    • Two stage design

  • Ewing’s Secondary cohort (all other Ewing’s patients)

    • Relapse > 24 months (or ≤ 24 months 1 chemo regimen)

    • 35 patients

    • Two stage design


Sarc011 no21157 statistical considerations1

SARC011/NO21157Statistical Considerations

  • Osteosarcoma, Rhabdomyosarcoma, Synovial Sarcoma

    • 35 patients

    • Two stage design

  • Other Sarcomas

    • 20 patients for each of 5 other subtypes

    • Two stage design within each of the 5 subtypes


Who criteria

WHO Criteria

Bi-dimensional measurements

Complete response (CR)

Disappearance of all known disease

Partial response (PR)

≥ 50% decrease

Stable disease (SD)

No 50% decrease & no 25% increase

Progressive disease (PD)

≥ 25% increase


Interim analysis

Interim Analysis

  • Open to Recruitment:

    • Ewing’s 1

    • Ewing’s 2

    • Rhabdomyosarcoma

    • Other Sarcomas

  • Closed

    • Osteosarcoma

  • Undergoing interim analysis

    Synovial Sarcoma


Sarc011 no21157 patient enrollment

SARC011/NO21157Patient Enrollment

  • 28 centers are activated and open to enroll patients

  • n = 189 (177 eligible)

  • Age:

    • 12-86 yrs

  • Gender: (n=190*)

    • 118 Male

    • 72 Female

      *includes patient in screening

      data from Nov 1st, 2008


Sarc011 no21157

Patient Enrollment-All Cohorts

189 enrolled 177 patients are eligible- data from Nov 1st, 2008


Sarc011 no21157

Patient Enrollment-Ewing’s

68 eligible Ewing’s patients- data from Nov 1st, 2008


Patient enrollment by week

Patient Enrollment by week

All Patients

Ewing’s Patients


Patient enrollment by month

Patient Enrollment by month


Sarc011 no21157

Ewing’s – Only 15% of Enrolled Patients < 18

data from Nov 1st, 2008


Sarc011 no21157 protocol violations

SARC011/NO21157 Protocol Violations

Patients must have measurable disease

Index lesions must not be in prior site of radiation

Index lesions must be ≥ 10mm by spiral CT or ≥ 20mm by conventional techniques

Central pathology confirmation required within 6 weeks

Dose of R1507 must not be adjusted unless there is a 10% change in weight


Where do we need your help

Where do we need your help?

  • Ensuring patients are eligible

  • Enrolling pediatric patients

  • Enrolling Ewing’s 1 patients

  • Enrolling patients to the CBP

  • Sending samples for central path review

  • Sending pre study, baseline and efficacy scans to Bioimaging

  • Entering data answering queries


Sarc011 no21157 enrollment by cohort

SARC011/NO21157Enrollment by Cohort

Nov 1, 2008


Sarc011 no21157 enrollment by others cohort

SARC011/NO21157Enrollment by Others Cohort

Nov 1, 2008

Clear Cell Sarcoma


Sarc011 no21157 histologic diagnosis n 189

SARC011/NO21157Histologic Diagnosis (n=189)

Nov 1, 2008

SS: synovial sarcoma

OGS: osteosarcoma

EWS-1: Ewing’s sarcoma primary

EWS-2: Ewing’s sarcoma secondary

MLS: myxoid liposarcoma

EMC: extraskeletal myxoid chondrosarcoma

DSRCT: desmoplastic small round cell tumor

CCS: clear cell sarcoma

ASPS: alveolar soft part sarcoma

RMS: rhabdomyosarcoma


Sarc011 no21157 saes

SARC011/NO21157 SAEs

Nov 1, 2008

*1 event of Thrombocytopenia, Adrenal Hemorrhage and Pulmonary embolism attributed to drug


Sarc011 no21157 saes1

SARC011/NO21157 SAEs

Nov 1, 2008


Sarc011 no21157

Thank you


Background slides

Background slides


Sarc011 no21157 background

SARC011/NO21157 Background

The outcome for patients with recurrent sarcomas

is uniformly poor

Rhabdomyosarcoma

n=605

Med age 8y [0-20y]

Pappo et al.

JCO, 17, 3487, 1999

27


Sarc011 no21157

The outcome for patients with recurrent sarcomas

is uniformly poor

SARC011/NO21157 Background

Ewing Sarcoma

Jürgens

ASCO 2007

Asbtract 10012

1

28


Sarc011 no21157

SARC011/NO21157 Background

The outcome for patients with recurrent sarcomas

is uniformly poor

Osteosarcoma

n=575

Median age at Diagnosis

15.5 y [2.2 -68.2y]

Kempf-Bielack et al.

JCO, 23, 559, 2005

2

29


Sarc011 no21157

30


Sarc 011 background

SARC 011Background

  • R 1507 is a IGF-1 MoAb of the IgG1 subclass that binds the extracellular domain of IGF-1R and inhibits receptor activation

  • Main adverse events in about 40% of patients included GI, and fatigue but NO DLT

  • 4/59 HAHA (3 preexisting)

  • 9 mg/kg weekly. Half life 7 days

  • Responses:

    • 2/7 PR EWS

    • 5/19 SD


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