Phase i study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors

OncoImmunology

Volumn 2, Issue 1, 2013, Pages

  Vonderheide, Robert H ^a   Burg, Jennifer M ^a   Mick, Rosemarie ^a,b   Trosko, Jennifer A ^a   Li, Dongguang ^c   Shaik, M Naveed ^c   Tolcher, Anthony W ^d   Hamid, Omid ^e  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c PFIZER INC   (United States)

^d South Texas Accelerated Research Therapeutics   (United States)

^e Angeles Clinic and Research Institute   (United States)

Author keywords

893; CD40; Chemotherapy; Clinical trial; CP 870; Monoclonal antibody; T cells

Indexed keywords

CARBOPLATIN; CP 870893; PACLITAXEL;

ADULT; ADVANCED CANCER; ADVERSE OUTCOME; AGED; ALOPECIA; ANEMIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; BACKACHE; BRAIN HEMORRHAGE; CANCER COMBINATION CHEMOTHERAPY; CD3+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL SPECIFICITY; CELLULAR IMMUNITY; CEREBROVASCULAR ACCIDENT; CHILL; CLINICAL ARTICLE; CLINICAL EVALUATION; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYTOKINE RELEASE SYNDROME; DECREASED APPETITE; DIARRHEA; DIZZINESS; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FEVER; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TREATMENT FAILURE; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; GASTROESOPHAGEAL REFLUX; HEART ARRHYTHMIA; HEMATURIA; HUMAN; HUMAN CELL; HYPOGEUSIA; HYPOMAGNESEMIA; IMMUNOMODULATION; IMMUNOREGULATION; LEUKOPENIA; LYMPHEDEMA; LYMPHOCYTE COUNT; LYMPHOCYTE DEPLETION; LYMPHOCYTOPENIA; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MENTAL HEALTH; MULTICENTER STUDY; MYALGIA; NAUSEA; NEUTROPENIA; OPTIC NERVE INFARCTION; OUTCOME ASSESSMENT; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; SIDE EFFECT; SOLID TUMOR; STOMATITIS; THORAX PAIN; THROMBOCYTOPENIA; THROMBOSIS; TRANSIENT ISCHEMIC ATTACK; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; UPREGULATION; VOMITING;

EID: 84877805593     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.4161/onci.23033     Document Type: Article

References (13)

1. Vonderheide RH. Prospect of targeting the CD40 pathway for cancer therapy. Clin Cancer Res 2007; 13:1083-8; http://dx.doi. org/10.1158/1078-0432.CCR-06-1893.
2. van Kooten C, Banchereau J. CD40-CD40 ligand. J Leukoc Biol 2000; 67:2-17
3. Alexandroff AB, Jackson AM, Paterson T, Haley JL, Ross JA, Longo DL, et al. Role for CD40-CD40 ligand interactions in the immune response to solid tumours. Mol Immunol 2000; 37:515-26; http://dx.doi.org/10.1016/S0161-5890(00)00079-1.
4. Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011; 331:1612-6; http://dx.doi.org/10.1126/science.1198443.
5. Gladue RP, Paradis T, Cole SH, Donovan C, Nelson R, Alpert R, et al. The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice. Cancer Immunol Immunother 2011; 60:1009-17; http://dx.doi.org/10.1007/s00262-011-1014-6.
6. Vonderheide RH, Flaherty KT, Khalil M, Stumacher MS, Bajor DL, Hutnick NA, et al. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J Clin Oncol 2007; 25:876-83; http://dx.doi.org/10.1200/JCO.2006.08.3311.
7. Nowak AK, Robinson BW, Lake RA. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res 2003; 63:4490-6.
8. Rüter J, Antonia SJ, Burris HA 3rd, Huhn RD, Vonderheide RH. Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors. Cancer Biol Ther 2010; 10:983-93; http://dx.doi.org/10.4161/cbt.10.10.13251.
9. Pflugfelder A, Eigentler TK, Keim U, Weide B, Leiter U, Ikenberg K, et al. Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma. PLoS One 2011; 6:e16882; http://dx.doi.org/10.1371/journal.pone.0016882.
10. Hauschild A, Agarwala SS, Trefzer U, Hogg D, Robert C, Hersey P, et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol 2009; 27:2823-30; http://dx.doi.org/10.1200/JCO.2007.15.7636.
11. Hodi FS, Soiffer RJ, Clark J, Finkelstein DM, Haluska FG. Phase II study of paclitaxel and carboplatin for malignant melanoma. Am J Clin Oncol 2002; 25:283-6; http://dx.doi.org/10.1097/00000421-200206000-00016.
12. Domchek SM, Recio A, Mick R, Clark CE, Carpenter EL, Fox KR, et al. Telomerase-specific T-cell immunity in breast cancer: effect of vaccination on tumor immunosurveillance. Cancer Res 2007; 67:10546-55; http://dx.doi.org/10.1158/0008-5472.CAN-07-2765.
13. Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat 1979; 6:65-70.