Conatumumab: A novel monoclonal antibody against death receptor 5 for the treatment of advanced malignancies in adults

Expert Opinion on Biological Therapy

Volumn 11, Issue 11, 2011, Pages 1519-1524

  Bajaj, Madhuri ^a   Heath, Elisabeth I ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Conatumumab; Death receptor 5 agonist antibody; Therapy; TRAIL receptor

Indexed keywords

BEVACIZUMAB; BORTEZOMIB; CAPECITABINE; CARBOPLATIN; CONATUMUMAB; DEATH RECEPTOR 5; DOXORUBICIN; FLUOROURACIL; FOLINIC ACID; GANITUMAB; GEMCITABINE; IMMUNOGLOBULIN G1 ANTIBODY; IRINOTECAN; OXALIPLATIN; PACLITAXEL; PANITUMUMAB; VORINOSTAT;

ABDOMINAL PAIN; ADVANCED CANCER; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RELAPSE; CANCER SURVIVAL; COLORECTAL CANCER; COLORECTAL CARCINOMA; CREATINE KINASE BLOOD LEVEL; DRUG ACCUMULATION; DRUG BINDING; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FATIGUE; HEART FAILURE; HUMAN; HYPONATREMIA; IN VITRO STUDY; IN VIVO STUDY; LUNG EMBOLISM; LUNG NON SMALL CELL CANCER; LYMPHOMA; MONOTHERAPY; NAUSEA; NEUTROPENIA; NONHUMAN; PAIN; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; SIDE EFFECT; SOFT TISSUE SARCOMA; SOLID TUMOR; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; VOMITING;

ADULT; ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; HUMANS; NEOPLASMS; RECEPTORS, TNF-RELATED APOPTOSIS-INDUCING LIGAND; TREATMENT OUTCOME;

EID: 80053644400     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.2011.610788     Document Type: Article

References (19)

1. Griffith TS, Chin WA, Jackson GC, et al. Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J Immunol 1998;161:2833-40 (Pubitemid 28425704)
2. Biven K, Erdal H, Hagg M, et al. A novel assay for discovery and characterization of pro-apoptotic drugs and for monitoring apoptosis in patient sera. Apoptosis 2003;8:263-8 (Pubitemid 36749611)
3. Kelley SK, Ashkenazi A. Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol 2004;4:333-9 (Pubitemid 38987058)
4. Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 2005;5:876-85 (Pubitemid 41746032)
5. Kaplan-Lefko PJ, Graves JD, Zoog SJ, et al. Conatumumab, a fully human agonist antibody to death receptor 5, induces apoptosis via caspase activation in multiple tumor types. Cancer Biol Ther 2010;9:618-31
6. Herbst RS, Kurzrock R, Hong DS, et al. A first-in-human study of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res 2010;16:5883-91
7. Doi T, Murakami H, Ohtsu A, et al. Phase 1 study of conatumumab, a pro-apoptotic death receptor 5 agonist antibody, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 2010;published online 16 December 2010; doi: 10.1007/s00280-010-1544-1
8. Amgen. A Phase 1b/2 Study of AMG 655 in combination with Paclitaxel and Carboplatin for the first-line treatment of advanced non-small cell lung cancer. Clinicaltrials.gov NCT 00534027 Available from: http://clinicaltrials.gov/ct2/ show/NCT00534027? term=NCT00534027&rank=1
9. Rosevear HM, Lightfoot AJ, Griffith TS. Conatumumab, a fully human mAb against death receptor 5 for the treatment of cancer. Curr Opin Investig Drugs 2010;11:688-98
10. Marsters SA, Sheridan JP, Pitti RM, et al. A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol 1997;7:1003-6 (Pubitemid 28017080)
11. Martinez-Lorenzo MJ, Alava MA, Gamen S, et al. Involvement of APO2 ligand/TRAIL in activation-induced death of Jurkat and human peripheral blood T cells. Eur J Immunol 1998;28:2714-25 (Pubitemid 28425230)
12. Amgen. A Study of AMG 655 or AMG 479 in combination with Gemcitabine for treatment of metastatic pancreatic cancer. Clinicaltrials.gov NCT00630552 Available from: http://clinicaltrials.gov/ct2/show/NCT00630552? term=NCT00630552&rank=1
13. Amgen. Phase 1b/2 study of AMG 655 with mFOLFOX6 and Bevacizumab for first-line metastatic colorectal cancer. Clinicaltrials.gov NCT00625651 Available from: http://clinicaltrials.gov/ct2/show/NCT00625651? term=NCT00625651&rank=1
14. Amgen. Phase 1b/2 Study of AMG 655 with Doxorubicin for the first-line treatment of unresectable soft tissue sarcoma. Clinicaltrials.gov NCT00626704 Available from: http://clinicaltrials.gov/ct2/show/NCT00626704? term=NCT00626704&rank=1
15. Amgen. Phase 1b Lymphoma Study of AMG 655 in combination with Bortezomib or Vorinostat. Clinicaltrials. gov NCT00791011 Available from: http://clinicaltrials.gov/ct2/show/NCT00791011? term=NCT00791011&rank=1
16. Amgen. Phase 2 Safety & Efficacy of FOLFIRI in combination with AMG 479 or AMG 655 vs FOLFIRI in KRAS-mutant Metastatic Colorectal Carcinoma. Clinicaltrials.gov NCT00813605 Available from: http://clinicaltrials.gov/ct2/ show/NCT00813605? term=NCT00813605&rank=1
17. Amgen. AMG 655/Panitumumab combination metastatic colorectal cancer study. Clinicaltrials.gov NCT00630786 Available from: http://clinicaltrials.gov/ ct2/show/NCT00630786? term=NCT00630786&rank=1
18. Amgen. AMG 655 in combination with AMG 479 in advanced, refractory solid tumors. Clinicaltrials.gov NCT00819169 Available from: http://clinicaltrials. gov/ct2/show/NCT00819169? term=NCT00819169&rank=1
19. Radiation Therapy Oncology Group. Conatumumab, Gemcitabine Hydrochloride, Capecitabine, and Radiation Therapy in Treating patients with locally advanced pancreatic cancer. Clinicaltrials.gov NCT01017822 Available from: http://clinicaltrials.gov/ct2/show/NCT01017822? term=NCT01017822&rank=1