Table 1 |
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Summary of eleven first-in-human drugs presented at this year's ASCO meeting. |
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Drug name |
Target |
Route |
Tumor sites enrolled |
Common low-grade adverse effects |
Dose-limiting toxicities |
RPTD |
Clinical efficacy |
Phase II studies planned/o pen |
|
|
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BMS-663513 |
CD-137 agonist |
i.v. |
Melanoma Renal cell Ovarian |
Fatigue Rash/pruritis Diarrhea Fever |
Neutropenia Transaminitis |
TBD (range from 0.1–5 mg/kg every 3 weeks) |
6% PR 15% SD† |
Melanoma |
|
|
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CT-322 |
VEGFR-2 |
i.v. |
Misc. solid tumors and NHL |
Proteinuria Hypertension |
Proteinuria RPLS Retinal vascular occlusion |
MTD of 2 mg/kg/week, RPTD not specified |
49% SD† |
GBM |
|
|
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CVX-045 |
Thrombospondin |
i.v. |
Misc. solid tumors |
Fatigue GI Dyspnea Headache Dizziness |
None 1 radiation pneumonitis 1 death (bowel obstruction) |
12 mg/kg/week |
5% PR 33% SD |
TBD |
|
|
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GDC-0449 |
Smoothened |
oral |
Misc. solid tumors |
Dysguesia Hyponatremia Fatigue |
None |
150 mg daily |
11% PR 11% SD |
Colorectal Ovarian BCC |
|
|
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GRN163L |
Telomerase |
i.v. |
Misc. solid tumors |
Prolonged PTT GI Fatigue |
Thrombocytopenia One death (unknown cause) |
TBD |
TBD |
TBD |
|
|
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LY2181308 |
Survivin |
i.v. |
Misc. solid tumors |
Fever Fatigue Prolonged PTT Nausea |
Headache |
750 mg daily for 3 days, then weekly |
10% SD |
Prostate |
|
|
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PF-00562271 |
FAK |
oral |
Misc. solid tumors |
GI Headache Fatigue Dizziness |
Headache Nausea |
125 mg twice daily |
17% SD |
TBD |
|
|
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RAV12 |
RAAG12 |
i.v. |
GI cancers |
Diarrhea Abdominal discomfort Transaminitis |
Diarrhea Abdominal discomfort Transaminitis |
0.75 mg/kg twice weekly |
2% PR 20% SD† |
Pancreas Colorectal |
|
|
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RTA 402 |
NF-κB and STAT3 |
oral |
Misc. solid tumors and NHL |
GI Fatigue Anorexia Dysguesia |
ALT elevation |
900 mg/day |
7% CR + PR 40% SD† |
Pancreas Melanoma |
|
|
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XL765 |
PI3K and mTOR |
oral |
Misc. solid tumors |
Transaminitis Diarrhea Anorexia Fatigue |
Transaminitis Diarrhea |
Possibly 60 mg twice daily |
26% SD |
TBD |
|
|
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Survivin vaccine |
Survivin |
s.c. |
Melanoma |
Injection site reactions Fever Lymph node swelling |
None |
TBD |
8% CR+PR |
TBD |
|
|
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†Clinical efficacy was not available at time of presentation for all patients enrolled in these studies, therefore these response rates do not represent the whole study cohort and may change in the future Abbreviations: TBD – to be determined; MTD – maximum tolerated dose; RPTD – recommended phase II dose; CR – complete response; PR – partial response; SD – stable disease; i.v. – intravenous; Misc – miscellaneous; NHL – non-Hodgkin's lymphoma; GBM – gliobastome multiforme; PTT – partial thromboplastin time; s.c. – deep subcutaneous; GI – gastrointestinal (including all 3 of nausea/vomiting/diarrhea); BCC – basal cell carcinoma; RPLS – Reversible posterior leucoencephalopathy syndrome |
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Molckovsky and Siu Journal of Hematology & Oncology 2008 1:20 doi:10.1186/1756-8722-1-20 |
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