Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: Preclinical characterization and phase I clinical trial

Clinical Cancer Research

Volumn 21, Issue 1, 2015, Pages 49-59

  Di Cosimo, Serena ^a,g   Sathyanarayanan, Sriram ^b,j   Bendell, Johanna C ^c   Cervantes, Andrés ^d   Stein, Mark N ^e   Braña, Irene ^a,h   Roda, Desamparados ^d   Haines, Brian B ^b   Zhang, Theresa ^b   Winter, Christopher G ^b   Jha, Sharda ^b   Xu, Youyuan ^b   Frazier, Jason ^b   Klinghoffer, Richard A ^b   Leighton Swayze, Ann ^b   Song, Yang ^b   Ebbinghaus, Scot ^b   Baselga, José ^f,i  

^a HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^b MERCK RESEARCH LABORATORIES   (United States)

^c SARAH CANNON RESEARCH INSTITUTE   (United States)

^d UNIVERSITY OF VALENCIA   (Spain)

^e RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^f MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^g NATIONAL CANCER INSTITUTE   (Italy)

^h PRINCESS MARGARET HOSPITAL   (Canada)

ⁱ MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^j Jounce Therapeutics   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; ANTIDIABETIC AGENT; DALOTUZUMAB; FLUORODEOXYGLUCOSE F 18; INSULIN; LENTIVIRUS VECTOR; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN KINASE B; RIDAFOROLIMUS; SHORT HAIRPIN RNA; ANTINEOPLASTIC AGENT; IGF1R PROTEIN, HUMAN; MONOCLONAL ANTIBODY; MTOR PROTEIN, HUMAN; RAPAMYCIN; SOMATOMEDIN RECEPTOR; TARGET OF RAPAMYCIN KINASE;

ADVANCED CANCER; ANEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; ASTHENIA; BODY WEIGHT; BREAST CANCER; CANCER CELL LINE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CHONDROSARCOMA; COLON CANCER; COLORECTAL CANCER; COMPUTER ASSISTED EMISSION TOMOGRAPHY; CONTROLLED STUDY; DECREASED APPETITE; DESMOPLASTIC ROUND CELL TUMOR; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; DRUG SCREENING; DRUG SENSITIVITY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ELECTROCARDIOGRAPHY; ELECTROLYTE DISTURBANCE; ENDOMETRIUM CANCER; ENZYME ACTIVATION; EPISTAXIS; EWING SARCOMA; FATIGUE; FEMALE; FEVER; HEALTH STATUS; HEMATOLOGIC DISEASE; HISTOPATHOLOGY; HOSPITALIZATION; HUMAN; HUMAN CELL; HYPERCHOLESTEROLEMIA; HYPERGLYCEMIA; HYPERTRIGLYCERIDEMIA; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; INFECTION; LEIOMYOSARCOMA; LIPOSARCOMA; LUNG ADENOCARCINOMA; MAJOR CLINICAL STUDY; MELANOMA; MONOTHERAPY; MUCOSA INFLAMMATION; NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; NONHUMAN; OSTEOSARCOMA; OVARY CANCER; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PROGRESSION FREE SURVIVAL; RASH; RECOMMENDED DRUG DOSE; RECTUM CANCER; SALIVARY GLAND CANCER; SARCOMA; SKIN; SOLID TUMOR; STOMATITIS; SYNOVIAL SARCOMA; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; VITAL SIGN; VOMITING; ADULT; AGED; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; CLINICAL TRIAL; DRUG EFFECTS; GENETICS; IMMUNOLOGY; METABOLISM; MIDDLE AGED; MULTICENTER STUDY; PATHOLOGY; SIGNAL TRANSDUCTION;

ADULT; AGED; ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; HUMANS; MIDDLE AGED; RECEPTORS, SOMATOMEDIN; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84920518981     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-14-0940     Document Type: Article

References (32)

1. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501.
2. Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002;296:1655-7.
3. Creighton CJ, Casa A, Lazard Z, Huang S, Tsimelzon A, Hilsenbeck SG, et al. Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis. J Clin Oncol 2008;26:4078-85.
4. Creighton CJ, Fu X, Hennessy BT, Casa AJ, Zhang Y, Gonzalez-Angulo AM, et al. Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res 2010;12:R40.
5. Loi S, Haibe-Kains B, Desmedt C, Wirapati P, Lallemand F, Tutt AM, et al. Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics 2008;9:239.
6. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 2008;68:6084-91.
7. Fox EM, Miller TW, Balko JM, Kuba MG, Sánchez V, Smith RA, et al. A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res 2011;71:6773-84.
8. Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol 2011;29:4452-61.
9. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007;12:9-22.
10. Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009;27:2278-87.
11. Di Cosimo S. Controversies in breast cancer: the mammalian target of rapamycin as a target for breast cancer therapy. Breast Cancer Res 2009;11(Suppl 3):S25.
12. Di Cosimo S, Seoane J, Guzman M, Rojo F, Jimenez J, Anido J, et al. Combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (E) with the insulin like growth factor-1-receptor (IGF-1-R) inhibitor NVP-AEW-541: A mechanistic based anti-tumor strategy. J Clin Oncol 2005;23(Suppl):3112.
13. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006;66:1500-8.
14. Tabernero J, Rojo F, Calvo E, Burris H, Judson I, Hazell K, et al. Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol 2008;26:1603-10.
15. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011;19:58-71.
16. Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 2011;30:2547-57.
17. Skolnik JM, Barrett JS, Jayaraman B, Patel D, Adamson PC. Shortening the timeline of pediatric phase I trials: the rolling six design. J Clin Oncol 2008;26:190-5.
18. Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodríguez-Braun E, et al. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res 2011;17:6304-12.
19. Loboda A, Nebozhyn M, Klinghoffer R, Frazier J, Chastain M, Arthur W, et al. A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors. BMC Med Genomics 2010;3:26.
20. Zha J, O'Brien C, Savage H, Huw LY, Zhong F, Berry L, et al. Molecular predictors of response to a humanized anti-insulin-like growth factor-I receptor monoclonal antibody in breast and colorectal cancer. Mol Cancer Ther 2009;8:2110-21.
21. Mita MM, Britten CD, Poplin E, et al. Deforolimus trial 106 - a phase I trial evaluating 7 regimens of oral deforolimus (AP23573, MK-8669). J Clin Oncol 2008;26 (Suppl):3509.
22. Sankhala K, Mita A, Kelly K, Mahalingam D, Giles F, Mita M. The emerging safety profile of mTOR inhibitors, a novel class of anticancer agents. Target Oncol 2009;4:135-42.
23. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56.
24. Gualberto A, Pollak M. Emerging role of insulin-like growth factor receptor inhibitors in oncology: early clinical trial results and future directions. Oncogene 2009;28:3009-21.
25. Chan S, Scheulen ME, Johnston S, Mross K, Cardoso F, Dittrich C, et al. Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 2005;23:5314-22.
26. Ellard SL, Clemons M, Gelmon KA, Norris B, Kennecke H, Chia S, et al. Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol 2009;27:4536-41.
27. Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009;101:736-50.
28. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869-74.
29. de Ronde JJ, Hannemann J, Halfwerk H, Mulder L, Straver ME, Vrancken Peeters MJ, et al. Concordance of clinical and molecular breast cancer subtyping in the context of preoperative chemotherapy response. Breast Cancer Res Treat 2010;119:119-26.
30. Massarweh S, Osborne CK, Creighton CJ, Qin L, Tsimelzon A, Huang S, et al. Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res 2008;68:826-33.
31. Casa AJ, Dearth RK, Litzenburger BC, Lee AV, Cui X. The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance. Front Biosci 2008;13:3273-87.
32. Baselga J, Campone M, Piccart M, Burris HA III, Rugo HS, Sahmoud T, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012;366:520-9.