A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors

Investigational New Drugs

Volumn 36, Issue 5, 2018, Pages 836-847

  King, Gentry T ^a   Eaton, Keith D ^b   Beagle, Brandon R ^c   Zopf, Christopher J ^c   Wong, Gilbert Y ^c   Krupka, Heike I ^c   Hua, Steven Y ^c   Messersmith, Wells A ^a   El Khoueiry, Anthony B ^d  

^a UNIVERSITY OF COLORADO CANCER CENTER   (United States)

^b SEATTLE CANCER CARE ALLIANCE   (United States)

^c PFIZER INC   (United States)

^d UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Antibody drug conjugate; Auristatin; Phase 1; Solid tumors; Trop 2

Indexed keywords

ANTIBODY DRUG CONJUGATE; ANTINEOPLASTIC AGENT; CELL SURFACE PROTEIN; PF 06664178; TROPHOBLAST CELL SURFACE ANTIGEN 2; UNCLASSIFIED DRUG; AMINOBENZOIC ACID DERIVATIVE; ANTIBODY CONJUGATE; AURISTATIN; CELL ADHESION MOLECULE; OLIGOPEPTIDE; TACSTD2 PROTEIN, HUMAN; TUMOR ANTIGEN;

ADULT; ADVANCED CANCER; ANTIBODY BLOOD LEVEL; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ARTICLE; BREAST CANCER; BULLOUS DERMATITIS; CANCER PATIENT; CHILL; CLINICAL ARTICLE; COHORT ANALYSIS; CONSTIPATION; CYTOTOXICITY; DECREASED APPETITE; DIARRHEA; DOSE CALCULATION; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG EXPOSURE; DRUG FATALITY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; HUMAN TISSUE; INFUSION RELATED REACTION; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; OPEN STUDY; OVARY CANCER; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; PRURITUS; RASH; SOLID MALIGNANT NEOPLASM; TOXIC EPIDERMAL NECROLYSIS; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; CLINICAL TRIAL; METABOLISM; NEOPLASM; TREATMENT OUTCOME;

AMINOBENZOATES; ANTIGENS, NEOPLASM; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL ADHESION MOLECULES; EXANTHEMA; FEMALE; HUMANS; IMMUNOCONJUGATES; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; NEUTROPENIA; OLIGOPEPTIDES; TREATMENT OUTCOME;

EID: 85042791261     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-018-0560-6     Document Type: Article

References (23)

1. Lambert JM, Morris CQ (2017) Antibody-drug conjugates (ADCs) for personalized treatment of solid tumors: a review. Adv Ther 34:1–21
2. Beck A, Goetsch L, Dumontet C, Corvaïa N (2017) Strategies and challenges for the next generation of antibody–drug conjugates. Nat Rev Drug Discov 16:315–337
3. Lipinski M, Parks DR, Rouse R V, Herzenberg L a (1981) Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc Natl Acad Sci U S A 78:5147–5150
4. Bignotti E, Zanotti L, Calza S et al (2012) Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma. BMC Clin Pathol 12:22
5. Trerotola M, Cantanelli P, Guerra E et al (2013) Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene 32:222–233
6. Fong D, Moser P, Krammel C et al (2008) High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer 99:1290–1295
7. Ning S, Guo S, Xie J et al (2013) TROP2 correlates with microvessel density and poor prognosis in hilar cholangiocarcinoma. J Gastrointest Surg 17:360–368
8. Zhao W, Zhu H, Zhang S et al (2016) Trop2 is overexpressed in gastric cancer and predicts poor prognosis. Oncotarget 7:6136–6145
9. Ohmachi T, Tanaka F, Mimori K et al (2006) Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 12:3057–3063
10. Guerra E, Trerotola M, Aloisi AL et al (2013) The Trop-2 signalling network in cancer growth. Oncogene 32:1594–1600
11. Cubas R, Li M, Chen C, Yao Q (2009) Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochim Biophys Acta - rev. Cancer 1796:309–314
12. Strop P, Tran T-T, Dorywalska M et al (2016) RN927C, a site-specific Trop-2 antibody-drug conjugate (ADC) with enhanced stability, is highly efficacious in preclinical solid tumor models. Mol Cancer Ther 15:2698–2708
13. Strop P, Liu SH, Dorywalska M et al (2013) Location matters: site of conjugation modulates stability and pharmacokinetics of antibody drug conjugates. Chem Biol 20:161–167
14. Maderna A, Doroski M, Subramanyam C et al (2014) Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications. J Med Chem 57:10527–10543. 10.1021/jm501649k
15. O’quigley J, Pepe M, Fisher L (1990) Continual reassessment method: a practical Design for Phase 1 clinical trials in cancer. Biometrics 46103149:33–48
16. Iasonos A, O’Quigley J (2014) Adaptive dose-finding studies: a review of model-guided phase I clinical trials. J Clin Oncol 32:2505–2511. 10.1200/JCO.2013.54.6051
17. Stepan LP, Trueblood ES, Hale K et al (2011) Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer therapeutic target. J Histochem Cytochem 59:701–710. 10.1369/0022155411410430
18. Ocean AJ, Starodub AN, Bardia A et al (2017) Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: safety and pharmacokinetics. Cancer. 10.1002/cncr.30789
19. Heist RS, Guarino MJ, Masters G et al (2017) Therapy of advanced non–small-cell lung cancer with an SN-38-anti-trop-2 drug conjugate, sacituzumab govitecan. J Clin Oncol 35(24):2790–2797. 10.1200/JCO.2016.72.1894
20. Bardia A, Mayer IA, Diamond JR et al (2017) Efficacy and safety of anti-trop-2 antibody drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. J Clin Oncol 35(19):2141–2148. 10.1200/JCO.2016.70.8297
21. Ott PA, Hamid O, Pavlick AC et al (2014) Phase I/II study of the antibody-drug conjugate Glembatumumab Vedotin in patients with advanced melanoma. J Clin Oncol 32:3659–3666. 10.1200/JCO.2013.54.8115
22. Advani RH, Lebovic D, Chen A et al (2017) Phase I study of the anti-CD22 antibody-drug conjugate pinatuzumab vedotin with/without rituximab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res 23:1167–1176. 10.1158/1078-0432.CCR-16-0772
23. Devay RM, Delaria K, Zhu G et al (2017) Improved lysosomal trafficking can modulate the potency of antibody drug conjugates. Bioconjug Chem 28:1102–1114