Early clinical development of ARQ 197, a selective, Non-ATP-competitive inhibitor targeting MET tyrosine kinase for the treatment of advanced cancers

Oncologist

Volumn 16, Issue 6, 2011, Pages 788-799

  Adjei, Alex A ^a   Schwartz, Brian ^b   Garmey, Edward ^b  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

^b ARQULE INC   (United States)

Author keywords

C MET; EGFR; Epithelial growth factor inhibitor; Hepatocyte growth factor; Kinase receptor inhibitor

Indexed keywords

CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEMCITABINE; IRINOTECAN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PEMETREXED; PLACEBO; SCATTER FACTOR RECEPTOR; SORAFENIB; TIVANTINIB; VASCULOTROPIN INHIBITOR;

ADVANCED CANCER; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; BONE METASTASIS; BREAST CANCER; COLON CANCER; COLORECTAL CANCER; COMBINATION CHEMOTHERAPY; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG COMPETITION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG ERUPTION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG INTERMITTENT THERAPY; DRUG METABOLISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; DRUG TRANSFORMATION; DRUG WITHDRAWAL; DYSPNEA; ENZYME INHIBITION; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL DISEASE; GERM CELL TUMOR; HAND FOOT SYNDROME; HUMAN; IC 50; KIDNEY CARCINOMA; LEUKOPENIA; LIVER CELL CARCINOMA; LIVER METASTASIS; LUNG NON SMALL CELL CANCER; MAXIMUM PLASMA CONCENTRATION; MELANOMA; MONOTHERAPY; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NONHUMAN; OVERALL SURVIVAL; PANCREAS CANCER; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROSTATE CANCER; RECOMMENDED DRUG DOSE; SEPSIS; SINGLE DRUG DOSE; SINUS BRADYCARDIA; STOMACH CANCER; THROMBOCYTOPENIA; UNSPECIFIED SIDE EFFECT; VOMITING;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CAMPTOTHECIN; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; HEPATOCYTE GROWTH FACTOR; HUMANS; MICE; NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MET; PYRROLIDINONES; QUINAZOLINES; QUINOLINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTORS, GROWTH FACTOR;

EID: 79959609860     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2010-0380     Document Type: Article

References (46)

1. Furge KA, Zhang YW, Vande Woude GF. Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene 2000;19:5582-5589.
2. Birchmeier C, Gherardi E. Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol 1998;8:404-410.
3. Birchmeier C, Birchmeier W, Gherardi E et al. Metastasis, motility and more. Nat Rev Mol Cell Biol 2003;4:915-925.
4. Zhang YW, Vande Woude GF. HGF/SF-met signaling in the control of branching morphogenesis and invasion. JCell Biochem 2003;88:408-417.
5. Jiang W, Hiscox S, Matsumoto K et al. Hepatocyte growth factor/scatter factor, its molecular, cellular and clinical implications in cancer. Crit Rev Oncol Hematol 1999;29:209-248.
6. Toschi L, Janne PA. Single-agent and combination therapeutic strategies to inhibit hepatocyte growth factor/MET signaling in cancer. Clin Cancer Res 2008;14:5941-5946.
7. Jiang WG, Hiscox SE, Parr C et al. Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. Clin Cancer Res 1999;5:3695-3703.
8. Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 2008;7:504-516.
9. Schmidt L, Duh FM, Chen F et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997;16:68-73.
10. Lee JH, Han SU, Cho H et al. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 2000;19:4947-4953.
11. Heideman DA, Snijders PJ, Bloemena E et al. Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma. J Pathol 2001; 194:428-435.
12. Derksen PW, de Gorter D. J, Meijer HP et al. The hepatocyte growth factor/ Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia 2003;17:764-774.
13. Beroukhim R, Getz G, Nghiemphu L et al. Assessing the significance of chromosomal aberrations in cancer: methodology and application to gli-oma. Proc Natl Acad Sci U S A 2007;104:20007-20012.
14. Zeng Z, Weiser MR, D'Alessio M et al. Immunoblot analysis of c-Met expression in human colorectal cancer: overexpression is associated with advanced stage cancer. Clin Exp Metastasis 2004;21:409-417.
15. Christensen JG, Burrows J, Salgia R. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett 2005;225:1-26.
16. Cipriani NA, Abidoye OO, Vokes E et al. MET as a target for treatment of chest tumors. Lung Cancer 2009;63:169-179.
17. Bean J, Brennan C, Shih JY et al. MET amplification occurs withor without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 2007;104:20932-20937.
18. Munshi N, Jeay S, Li Y et al. ARQ197, anovel and selective inhibitorof the human c-Met receptor tyrosin kinase with anti-tumor activity. Mol Cancer Ther 2010;9:1544-1553.
19. Jeay S, Munshi N, Hill J et al. ARQ 197, a highly selective small molecule inhibitor of c-Met, with selective antitumor properties in a broad spectrum of human cancer cells. Paper presented at: 98th AACR Annual Meeting, Los Angeles, CA, April 14, 2007; Abstract 2369.
20. Jarvis LM. One pill, many uses. Chem Eng News 2007;85:15-23.
21. Underiner TL, Herbertz T, Miknyoczki SJ. Discovery of small molecule c-Met Inhibitors: evolution and profiles of clinical candidates. Anticancer Agents Med Chem 2010;10:7-27.
22. Pan BS, Chan GK, Chenard M. MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res 2010;70:1524-1533.
23. Gu X, Wang C, Yu Y et al. Inhibition of HGF/c-Met pathway by ARQ 197: characterization of pharmacodynamic markers in vitro and in vivo. Poster presented at: 2009 AACR Annual Meeting, Denver, CO, April 18, 2009; Abstract 1748.
24. Anderson K, Li C, Moreau J et al. ARQ 197, a small molecule inhibitor of c-met, prevents bone metastasis in a humanized mouse model ofbreast cancer. Poster presented at: AACR-NCI-EORTC International Conference B184, San Francisco, CA, October 22, 2007; Abstract B184.
25. Li Y, Chen D, Zhou W et al. Broad spectrum anti-cancer activity of ARQ 197, a highly selective oral c-Met inhibitor, in multiple xenograft models. Poster presented at: 98th AACR Annual Meeting; April 14-18, 2007, Los Angeles, CA; Poster 2216.
26. Savage RE, Zhong C, Hall T et al. In vitro ADME Properties of ARQ-197. Comparison to in vivo data. Poster presented at: 99th AACR Annual Meeting, Philadelphia, PA, April 12, 2009; Poster 1291.
27. Yap TA, Barriuso J, Frentzas S et al. Pharmacokinetic (PK) and pharma-codynamic (PD) phase I study of an oral c-Met inhibitor ARQ197 reaches maximum tolerated dose (MTD) in a twice daily (bid) dosing schedule. Eur J Cancer 2008;6(12 suppl):Abstract 386.
28. Santoro A, Simonelli M, Zucali P. A Phase Ib safety trial of ARQ 197 in cirrhotic patients with hepatocellular carcinoma (HCC). Poster presented at: American Society of Clinical Oncology Gastrology; 2010; Poster 1961.
29. Laux I, Goldman J, Goldman J et al. Phase I dose escalation trial (ARQ 197-111) evaluating combination of selective c-Met inhibitor ARQ 197 and erlotinib. American Society of Clinical Oncology 2010. J Clin Oncol 2009;27(15):3549.
30. Rosen L, Senzer N, Nemunaitis J et al. Phase 1 dose escalation study and signs of anti-metastatic activity of ARQ 197, a selective c-Met inhibitor. Paper presented at: AACR-NCI-EORTC International Conference, San Francisco, CA, October 22, 2007; Abstract B91.
31. Mekhail T, Rich T, Rosen L et al. Final results: a dose escalation phase I study of ARQ 197, a selective c-Met inhibitor, in patients with metastatic solid tumors. J Clin Oncol 2009;27(15s):3548.
32. Garcia A, Rosen L, Cunningham C et al. Phase 1 study of ARQ 197, a selective inhibitor of the c-Met RTK in patients with metastatic solid tumors reaches recommended phase 2 dose. J Clin Oncol 2007;25(suppl 18):3525.
33. Yap TA, Frentzas S, Tunuriu N et al. Final results of a pharmacokinetic (PK) and pharmacodynamic (PD) phase I trial of ARQ 197 incorporating dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) studies investigating the antiangiogenic activity of selective c-Met inhibition. J Clin Oncol 2009;27(15):3523.
34. Goldberg J, Demetri GD, Choy E et al. Preliminary results from a phase II studyof ARQ 197inpatients with microphthalmia transcription factor family (MiT)-associated tumors. J Clin Oncol 2009;27(15):10502.
35. Adjei AA, Sosman J, Dy GK et al. A Phase 1 dose-escalation trial of the c-MET inhibitor ARQ 197 administered in combination with sorafenib in adult patients with advanced solid tumors. Poster presented at: American Society ofClinical Oncology meeting, Chicago, IL, June 4-8,2010; Poster 3024.
36. Goldman J, Rosen L, Laux I et al. Phase I dose escalation trial (ARQ 197- 111) evaluating combination of selective c-Met inhibitor ARQ 197 and er-lotinib. Oral presentation at: IASLC 13th World Conference on Lung Cancer; August 1, 2009; San Francisco, CA, USA; Presentation A6.5.
37. Santoro A, Simonelli M, Zucali P et al. Preliminary results from ARQ 197- 144: a phase 1b safety trial evaluating ARQ 197 in cirrhotic patients with hepatocellular carcinoma (HCC). Poster presented at: American Society of Clinical Oncology meeting, Chicago, IL, June 4-8, 2010; Poster 1961.
38. Zucali P, Santoro A, Rodriguez-Lope C et al. Final results from ARQ 197- 114: a Phase 1b safety trial evaluating the c-MET inhibitor ARQ-197 in cirrhotic patients with hepatocellular carcinoma. Poster presented at: American Society of Clinical Oncology, Chicago, IL, June 4 - 8, 2010; Poster 4137.
39. Wagner A, Demetri GD, Choy E et al. Preliminary results from a Phase 2 studyof ARQ 197inpatients with microphthalmia transcription factor family (MiT) associated tumors. Oral presentation to: Connective Tissue Oncology Society, Miami, FL, November 26, 2009. Oral presentation 39313.
40. Borbath I, Santoro A, Van Laethem J et al. ARQ 197-215: a randomized, placebo-controlled phase 2 clinical trial evaluating the c-Met inhibitor, ARQ 197, in patients (pts) with hepatocellular carcinoma (HCC). Paper presented at: American Society of Clinical Oncology meeting, Chicago, IL, June 4-8, 2010; Abstract TPS215.
41. ClinicalTrials.gov. ARQ 197 for subjects with relapsed or refractory germ cell tumors. Avaiable at: http://www.clinicaltrials.gov/ct2/show/NCT01055067?term=nct01055067&rank=1. Accessed 2010.
42. Adjei AA, Puzanov I, Chai F et al. A phase 1 dose-escalation trial evaluating ARQ 197 administered in combination with sorafenib in adult patients with advanced solid tumors. Paper presented at: American Society of Clinical Oncology meeting, Chicago, IL, June 4-8, 2010; Abstract 3024.
43. Camacho L, Chen CL, Kazakin J et al. A phase 1b dose-escalation trial evaluating ARQ 197 administered in combination with gemcitabine to patients with advanced solid tumors. Paper presented at: American Society of Clinical Oncology meeting, Chicago, IL, June 4-8, 2010; Abstract e13008.
44. Schiller JH, Akerley WL, Brugger W et al. Results from ARQ 197-209: a global randomized placebo-controlled Phase 2 clinical trial comparing er-lotinib plus ARQ 197 to erlotinib plus placebo in previously treated EGFR-inhibitor naive patients with locally advanced or metastatic non-small cell lung cancer. Paper presented at: American Society of Clinical Oncology meeting oral presentation, Chicago, IL, June 4-8, 2010; Abstract LBA7502.
45. Sequist LV, Akerley WL, Brugger W et al. Final results from ARQ 197- 209: a global randomized placebo-controlled phase 2 clinical trial of erlotinib plus ARQ 197 versus erlotinb plus placebo in previously treated EGFR-inhibitor naïve patients with advanced non-small cell lung cancer (NSCLC). Paper presented at: European Society for Medical Oncology meeting, Milan, Italy, October 8-12, 2010; Abstract LBA7502.
46. ClinicalTrials.gov. ARQ 197 in combination with chemotherapy in patients with metastatic colorectal cancer. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01075048?term=nct01075048&rank=1. Accessed 2010.