Phase I dose escalation study of continuous oral dosing of OSI-906, an insulin like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitor, in patients with advanced solid tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2559-2559
Author(s):  
C. R. Lindsay ◽  
E. Chan ◽  
T. R. Evans ◽  
S. Campbell ◽  
P. Bell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Dose Escalation ◽  
Kinase Inhibitor ◽  
Plasma Concentrations ◽  
Median Number ◽  
Insulin Like Growth Factor ◽  
Dose Escalation Study ◽  
Molecule Inhibitor ◽  
Grade 3

2559 Background: OSI-906 is a potent small molecule inhibitor of IGF-1R, a receptor tyrosine kinase activated by insulin like growth factor, which is overexpressed in numerous malignancies and implicated in resistance to chemotherapy. Methods: Patients with advanced cancer entered escalating dose cohorts of OSI-906. Study objectives included assessment of: safety; determination of MTD; pharmacokinetics (PK), pharmacodynamics (PD) including IGF-1R levels in peripheral blood cells; and tumor response (RECIST). Results: To date, 32 pts have been treated (22M/10F, median age 62y) at 10, 20, 40, 75, 150, and 300 mg QD and at 20, 40 mg and 75 mg BID. Median number of weeks on trial was 6 (range 0–44). No DLTs have been observed. Hyperglycemia (5/20 pts) related to OSI-906 was transient and mild (grade 1 only). In addition to hyperglycemia, grade 1–2 nausea and vomiting (5/20 pts) were the most frequent related adverse events (AEs). There was grade 3 elevated lipase in 1 pt. At doses of 10–150 mg, OSI-906 exhibited linear PK, median terminal t1/2 ranged from 2.18–4.30 hr, AUC0-inf from 284–10200 ng.hr/mL, and Cmax 76.6–1440 ng/mL. There was no relationship between glucose or insulin levels and OSI-906 plasma concentrations. Stable disease > 12 weeks was seen in 7/20 pts (range 12–34 weeks), including 1 pt each with thymic (27 w), adrenocortical (28w), and colorectal (34w) cancer. PD data on IGF-1R phosphorylation will be presented. Conclusions: Plasma concentrations of OSI-906 achieved in this trial exceed concentrations required for antitumor efficacy in preclinical models. PD target modulation and preliminary anti-tumor activity have been observed. It is interesting to note that clinically meaningful hyperglycemia has yet to occur. Minimal toxicity was observed and further dose escalation is in progress. [Table: see text]

Phase 1 Dose Escalation Study of the Monoclonal Antibody Against the Insulin Like Growth Factor I Receptor CP-751,871 in Patients with Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1171-1171 ◽  
Author(s):  
Martha Q. Lacy ◽  
Melissa Alsina ◽  
Luisa Roberts ◽  
Rafael Fonseca ◽  
Carrie Melvin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Growth Factor ◽  
Dose Escalation ◽  
Therapeutic Approach ◽  
Phase 1 ◽  
Median Number ◽  
Insulin Like Growth Factor ◽  
Dose Escalation Study ◽  
Igf I

Abstract Background: CP-751,871, a fully human IgG2 subtype monoclonal antibody, is a potent and specific inhibitor of the insulin- like growth factor type I receptor (IGF-IR). The IGF-IR regulates the growth, survival, adhesion and invasiveness of multiple myeloma cells. High IGF-IR expression is observed in poor-prognostic subtypes of multiple myeloma and its inhibition has been long proposed as a potential therapeutic approach for treatment of this disease. Methods: A phase 1 dose escalation study was conducted to define the safety and tolerability, and to characterize the pharmacokinetic and pharmacodynamic (granulocyte surface IGF-IR expression and serum IGF-I levels) properties of CP-751,871 in patients with multiple myeloma. Patient’s eligibility included previously treated multiple myeloma in relapse or refractory phase including those less than complete remission to autologous stem cell transplant or tandem transplant. Results: Following informed consent and screening, 47 patients were enrolled into 11 dose-escalation cohorts of CP-751,871 at doses from 0.025 to 20 mg/Kg. Median patient age was 60 years. Median number of previous regimens was 4 (range 1–8). CP-751,871 was given as an IV infusion on Day 1 of 4-week cycles. Patients with a suboptimal response to CP-751,871 alone were eligible to receive CP-751,871 in combination with either oral dexamethasone and/or rapamycin at the discretion of the investigator. Twenty-seven patients received CP-751, 871 in combination with dexamethasone, while four patients received rapamycin in combination with either CP-751,871 or CP-751,871 and dexamethasone. Median number of treatment cycles was 3 (range 1–16). Ten patients were dosed at the highest cohort of 20 mg/Kg. No CP-751,871 related dose limiting toxicities were identified. Grade 3 toxicities were all observed at the 20 mg/Kg cohort (1 hyperglycemia, 1 anemia, 1 AST increase, 1 accidental fall, 1 muscle weakness). Plasma CP-751,871 exposure increased with dose, and the pharmacokinetic characteristics were consistent with target-mediated disposition. Granulocyte IGF-IR expression was maximally down-regulated for the entire duration of the dosing period at doses ≥1.5 mg/kg, indicating a saturation of circulating targets. CP-751,871 also led to a dose-dependent increase in circulating IGF-I concentrations. Tumor response was assessed according to Blade criteria. Two remissions and 4 partial remissions were reported in patients treated with different doses of CP-751,871 in combination with dexamethasone. Interestingly, the 2 patients with remission were previously found to be refractory to dexamethasone treatment. Conclusions: These data indicate that CP-751,871 is well tolerated either as a single agent or in combination with dexamethasone. Furthermore, CP-751,981 in combination with dexamethasone, may constitute a novel and effective therapeutic approach for patients with multiple myeloma.

An open-label phase I dose escalation study of KRN951, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 1 in a 4 week on, 2 week off schedule in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2034-2034 ◽  
Author(s):  
F. A. Eskens ◽  
A. Planting ◽  
L. Van Doorn ◽  
T. Isoe ◽  
K. Hayashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Drug Exposure ◽  
Kinase Inhibitor ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Growth Factor Receptor ◽  
Pharmacokinetic Analysis ◽  
Dose Escalation Study ◽  
Once Daily ◽  
Grade 3

2034 Background: KRN951 inhibits VEGF induced phosphorylation of VEGF receptors (VEGFR)2 and 1 (IC50 of 0.16 and 0.21 nM) and phosphorylation of c-Kit and Platelet Derived Growth Factor Receptor (PDGFR), (IC50 of 1.63 and 1.72 nM). Methods: The principal objectives of this study were (1) to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of KRN951 administered once daily (OD) for 28 days followed by 14 days off treatment, (2) to characterize safety and tolerability, (3) to characterize single and multiple dose pharmacokinetics, (4) to explore inhibitory effects on tumor blood flow, and (5) to look for evidence of antitumor activity. Results: 10 male and 5 female patients, median age 57 yrs (28–72) have been enrolled at dose levels of 1 mg (n=6), 2 mg (n=8), and 1.5 mg (n=1). The total number of courses given is 63 (1–15 per patient) At 2 mg DLT consisting of grade 3 asymptomatic proteinuria, grade 3 ataxia and grade 4 intracranial hemorrhage was seen in three patients. In the next-lower dose level of 1 mg one DLT (grade 3 fatigue) was seen. An intermediate dose of 1.5 mg is currently studied. Hypertension occurred in 14/15 patients but could be medically controlled. Pharmacokinetic analysis revealed dose dependent drug exposure and peak plasma concentrations. Plasma levels of sVEGFR2 decreased following exposure to KRN951. Exploratory analysis by means of Dynamic Contrast Enhanced MRI analysis indicated a decrease in tumorperfusion in selected patients. One confirmed partial response lasting more than 80 weeks in a patient with renal cell carcinoma was seen, and stable disease lasting more than 2 courses of treatment was seen in 6 patients. Conclusion: Once daily KRN951 can be administered safely when given for 28 days followed by 14 days off treatment. The recommended phase II dosing is currently being defined. No significant financial relationships to disclose.

Phase I and Pharmacologic Study of the Tyrosine Kinase Inhibitor SU101 in Patients With Advanced Solid Tumors

1999 ◽  
Vol 17 (4) ◽  
pp. 1095-1095 ◽  
Author(s):  
S. Gail Eckhardt ◽  
Jinee Rizzo ◽  
Kevin R. Sweeney ◽  
Gillian Cropp ◽  
Sharyn D. Baker ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Dose Escalation ◽  
Kinase Inhibitor ◽  
Plasma Concentrations ◽  
Dose Schedule ◽  
Malignant Neoplasms ◽  
Pharmacokinetic Studies ◽  
Entire Treatment Period ◽  
Moderate Nausea

PURPOSE: To evaluate the clinical feasibility and pharmacologic behavior of the platelet-derived growth factor (PDGF) tyrosine kinase inhibitor SU101, administered on a prolonged, intermittent dosing schedule to patients with advanced solid malignancies. PATIENTS AND METHODS: Twenty-six patients were treated with SU101 doses ranging from 15 to 443 mg/m2 as a 24-hour continuous intravenous (IV) infusion weekly for 4 weeks, repeated every 6 weeks. Pharmacokinetic studies were performed to characterize the disposition of SU101 and its major active metabolite, SU0020. Immunohistochemical staining of PDGF-α and -β receptors was performed on malignant tumor specimens obtained at diagnosis. RESULTS: Twenty-six patients were treated with 52 courses (187 infusions) of SU101. The most common toxicities were mild to moderate nausea, vomiting, and fever. Two patients experienced one episode each of grade 3 neutropenia at the 333 and 443 mg/m2 dose levels. Dose escalation of SU101 above 443 mg/m2/wk was precluded by the total volume of infusate required, 2.5 to 3.0 L. Individual plasma SU101 and SU0020 concentrations were described by a one-compartment model that incorporates both first-order formation and elimination of SU0020. SU101 was rapidly converted to SU0020, which exhibited a long elimination half-life averaging 19 ± 12 days. At the 443 mg/m2/wk dose level, trough plasma SU0020 concentrations during weeks 2 and 4 ranged from 54 to 522 μmol/L. Immunohistochemical studies revealed PDGF-α and -β receptor staining in the majority (15 of 19) of malignant neoplasms. CONCLUSION: SU101 was well tolerated as a 24-hour continuous IV infusion at doses of up to 443 mg/m2/wk for 4 consecutive weeks every 6 weeks. Although further dose escalation was precluded by infusate volume constraints, this SU101 dose schedule resulted in the achievement and maintenance of substantial plasma concentrations of the major metabolite, SU0020, for the entire treatment period.

Phase I dose-escalation study of pasireotide LAR in patients with advanced neuroendocrine tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15126-e15126 ◽  
Author(s):  
Alexandria T. Phan ◽  
Edward M. Wolin ◽  
Jennifer A. Chan ◽  
Jerry M. Huang ◽  
Michelle Hudson ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Somatostatin Receptor ◽  
Plasma Concentrations ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Dose Escalation Study ◽  
Best Response ◽  
Long Acting

e15126 Background: Somastatin analogs (SSA), including octreotide and lanreotide, bind predominantly to somatostatin receptor (SSTR) 2 and form the foundation of treatment for symptomatic neuroendocrine tumors (NET). Pasireotide, a novel SSA with a broad binding affinity (SSTR 1-3 and 5), is being explored for treatment of NET. A phase 1 dose-escalation study (NCT01364415) of pasireotide long-acting release (LAR; starting dose of 80 mg) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to characterize safety, tolerability, pharmacokinetics, and efficacy in pts with advanced NET. Methods: Pts with advanced, well- or moderately differentiated NET received pasireotide LAR beginning at a dose of 80 mg q28d. Successive cohorts will receive doses (up to 220 mg) guided by a Bayesian logistic regression model until MTD/RP2D is reached. Results: To date, 15 pts have been treated at 80 mg (n=6) and 120 mg (n=9). Median age is 59 (44-76) years. Primary tumor sites include small intestine (40%), pancreas (20%), and lung (13.3%). All pts received prior antineoplastic therapy; 93% received prior SSA. Median number of cycles of pasireotide was 6.68 (2-14) (1 cycle=28 days). 10 (67%) pts remain on treatment: 3 on 80 mg and 7 on 120 mg. 5 (33%) have discontinued (disease progression, 2 pts; withdrew consent, 2 pts; adverse event [AE], 1 pt). Median plasma concentrations of pasireotide increased with dose. No dose-limiting toxicities have been reported. Most frequent AEs were similar in both dose groups and included hyperglycemia (87%), diarrhea (53%), abdominal pain (47%), nausea (40%), anemia (33%), and fatigue (33%). Most AEs were mild/moderate. 2 pts (1 in each group) had grade 3 hyperglycemia. 4 (27%) and 2 (13%) pts had HbA1C increase from <6.5% at baseline to 6.5-<8% and ≥8%, respectively. 13 (87%) pts had radiographically stable disease as best response. More pts at 120 mg (50%) vs 80 mg (33%) achieved ≥50% reduction in chromogranin A. Conclusions: Pasireotide LAR up to 120 mg appears to be well tolerated in patients with advanced NET. The study is ongoing. Pasireotide represents a promising therapy for pts with NET. Clinical trial information: NCT01364415.

A phase I dose-escalation study of the safety and pharmacokinetics (PK) of XL184, a VEGFR and MET kinase inhibitor, administered orally to patients (pts) with advanced malignancies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14031-14031 ◽  
Author(s):  
R. Salgia ◽  
D. S. Hong ◽  
L. H. Camacho ◽  
C. S. Ng ◽  
L. Janisch ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Half Life ◽  
Kinase Inhibitor ◽  
Cell Cancer ◽  
Dose Escalation Study ◽  
Medullary Thyroid ◽  
Molecule Inhibitor ◽  
Advanced Malignancies ◽  
Terminal Half Life ◽  
Dose Levels

14031 Background: XL184 is a potent orally available small molecule inhibitor of MET and VEGFR2/KDR, and also inhibits KIT, RET, FLT3, and Tie-2. Methods: This is a ph 1 cohort dose escalation study. Pts with advanced malignancies are treated with 2 cycles of XL184 orally daily for 5 consecutive days every 2 weeks. Response is assessed every 8 wks by RECIST criteria and pts with SD or better receive maintenance therapy. Plasma markers of angiogenesis VEGF-A, sVEGFR2 and Ang2 are being analyzed. Results: A total of 25 pts with advanced malignancies have been treated across 7 dose levels: 0.08 to 5.12 mg/kg. A total of 10 pts have had SD lasting > 3 months. Three pts with medullary thyroid carcinoma (one of whom had a documented RET mutation) had substantial reductions in plasma calcitonin. Three pts have had stable disease for over 6 months, including 1 pt with carcinoid (20% decrease in liver metastases) and 1 pt with T- cell lymphoma (on treatment for >12 mos). One pt with papillary renal cell cancer, a disease that sometimes bears activating MET mutations, demonstrated 9% tumor reduction at first restaging. There have been no DLTs to date. Preliminary PK analysis (0.08–1.28 mg/kg) suggests linear PK with average Cmax values 34.2, 70, 198, 322 and 603 ng/mL following the fifth dose at 0.08, 0.16, 0.32, 0.64 and 1.28 mg/kg, respectively. The terminal half-life is 80–90 hrs, resulting in concentrations exceeding 200 ng/mL for 96 hours following the fifth dose at 1.28 mg/kg. Conclusions: XL184 appears generally well tolerated at doses tested to date. XL184 has a long terminal half-life. Early signs of antitumor activity have been observed, at doses not associated with toxicity, in patients with various cancers, including but not limited to those that may have RET (medullary thyroid) or MET (papillary renal) mutations. No significant financial relationships to disclose.

A phase lb, open-label, multicenter, dose-escalation study of the oral pan-PI3K inhibitor BKM120 in combination with the oral MEK1/2 inhibitor GSK1120212 in patients (pts) with selected advanced solid tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3003-3003 ◽  
Author(s):  
Philippe Bedard ◽  
Josep Tabernero ◽  
Razelle Kurzrock ◽  
Carolyn D. Britten ◽  
Anastasios Stathis ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Plasma Concentrations ◽  
Oral Intake ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Open Label ◽  
Dose Escalation Study ◽  
Grade 3 ◽  
Recommended Phase Ii Dose ◽  
Bayesian Logistic Regression

3003 Background: MAPK and PI3K/AKT signaling pathways regulate proliferation, differentiation and cell death in human cancers. Known interaction between the 2 pathways provides the rationale for combining both inhibitors in a phase I study. Methods: The objective is to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) for oral, daily administered, BKM120 + GSK1120212, mainly in pts with tumors with RAS/RAF mutations (mt). A Bayesian logistic regression model with overdose control guides the dose escalation of the treatment. Secondary objectives include safety, tolerability, PK and efficacy. Results: As of 22.09.11, 49 pts were treated with BKM120 + GSK1120212 as follows: 30mg + 0.5mg, 60mg + 0.5mg, 60mg + 1.0mg, 60mg + 1.5mg, 60mg + 2.0mg, 70mg + 1.5mg, 80mg + 1.0mg, 80mg + 1.5mg. 6 pts had dose-limiting toxicities (DLTs); all were reversible. Grade 3 DLTs were: 3 x stomatitis, 1 x dysphagia, 1 x LVEF decrease, 1 x CK increase, 1 x nausea, 1 x anorexia, 1 x decreased oral intake. MTD and/or RP2D for the combination have not been reached. Most common adverse events (AEs) (>25%), all grades and causality, were dermatitis acneiform, diarrhea (51% each); nausea (41%); vomiting (37%); rash (33%); asthenia (31%); CK increase, decreased appetite, pyrexia or stomatitis (29% each) and hyperglycemia (27%). There were 4 on-treatment deaths unrelated to treatment. AEs led to treatment discontinuation, 17 pts (35%) and interruptions/dose reductions, 25 pts (51%). Apparent steady-states of BKM120 and GSK1120212 were reached by day 28. Plasma concentrations of BKM120 in combination with GSK1120212 were lower than for monotherapy. Exposure to GSK1120212 with BKM120 was similar to that observed in monotherapy studies. 3 confirmed partial responses have been observed in pts with KRAS mt ovarian cancer; 2 lasting >9 months. 2 patients with BRAF mt melanoma, who had previously progressed on BRAF inhibitors, had stable disease, for 1 of whom treatment is still ongoing in cycle 6. Conclusions: BKM120 and GSK1120212 can be safely combined. Signs of clinical activity have been seen in pts with RAS/RAF mt tumors.

Phase I Pharmacokinetic and Pharmacodynamic Dose-Escalation Study of RG7160 (GA201), the First Glycoengineered Monoclonal Antibody Against the Epidermal Growth Factor Receptor, in Patients With Advanced Solid Tumors

2011 ◽  
Vol 29 (28) ◽  
pp. 3783-3790 ◽  
Author(s):  
Luis G. Paz-Ares ◽  
Carlos Gomez-Roca ◽  
Jean-Pierre Delord ◽  
Andres Cervantes ◽  
Ben Markman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phase I ◽  
Dose Escalation ◽  
Growth Factor Receptor ◽  
Dose Escalation Study ◽  
Epidermal Growth ◽  
Grade 3

Purpose We conducted a phase I dose-escalation study to characterize the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201), a humanized and glycoengineered immunoglobulin G1 anti–epidermal growth factor receptor (EGFR) monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity. Patients and Methods Seventy-five patients with advanced EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered every week, every 2 weeks, or every 3 weeks. Dose escalation followed a three-plus-three trial design. Results No maximum-tolerated dose was reached for any dosing schedule. Common adverse events (AEs) included rash (80% of patients), infusion-related reactions (77%), and hypomagnesemia (56%). Grades 3 and 4 AEs were rash (grade 3, 25%), infusion-related reaction (grade 3, 7%; grade 4, 1%), paronychia (grade 3, 3%), and hypomagnesemia (grade 3, 1%; grade 4, 1%). RG7160 exposure increased greater than proportionally over the 50- to 400-mg dose range (with greater than proportional decline in clearance) and approximately dose proportionally above 400 mg (where clearance plateaued). A marked reduction in circulating natural killer cells and increased infiltration of immune effector cells into skin rash were seen. Clinical efficacy included one complete response and two partial responses in patients with colorectal cancer (including one with KRAS mutation) and disease stabilization in 27 patients. Conclusion RG7160 had an acceptable safety profile with manageable AEs and demonstrated promising efficacy in this heavily pretreated patient cohort. On the basis of modeling of available PK parameters, the RG7160 dose selected for part two of this study is 1,400 mg on days 1 and 8 followed by 1,400 mg every 2 weeks.

Phase I Dose Escalation Study of Telatinib, a Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor 2 and 3, Platelet-Derived Growth Factor Receptor β, and c-Kit, in Patients With Advanced or Metastatic Solid Tumors

2009 ◽  
Vol 27 (25) ◽  
pp. 4169-4176 ◽  
Author(s):  
Ferry A.L.M. Eskens ◽  
Neeltje Steeghs ◽  
Jaap Verweij ◽  
Johan L. Bloem ◽  
Olaf Christensen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Phase I ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Vascular Endothelial ◽  
Dose Escalation Study ◽  
Grade 3 ◽  
Endothelial Growth Factor

PurposeTelatinib (BAY 57-9352) is an orally available tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -2, VEGFR-3, platelet-derived growth factor receptor-β, and c-Kit. This phase I dose escalation study was conducted to evaluate the safety and tolerability of telatinib, with additional pharmacokinetic, pharmacodynamic, and efficacy assessments.Patients and MethodsPatients with solid tumors refractory to standard therapies or with no standard therapy available were enrolled. Doses of continuously administered telatinib were escalated from 20 mg once daily to 1,500 mg twice daily.ResultsFifty-three patients were enrolled. Most frequently observed drug-related adverse events were nausea (26.4%; grade ≥ 3, 0%) and hypertension (20.8%; grade 3, 11.3%; grade 4, 0%). Two dose-limiting toxicities were observed: one poorly controlled hypertension (600 mg twice daily), and one grade 2 weight loss, anorexia, and fatigue (1,500 mg twice daily). A formal maximum-tolerated dose was not reached. Telatinib was rapidly absorbed, with median time to peak concentration (tmax) lower than 3 hours after dose. A nearly dose-proportional increase in exposure was observed with substantial variability. Telatinib half-life averaged 5.5 hours. Biomarker analyses showed dose-dependent increase in VEGF levels and decrease in plasma soluble VEGFR-2 levels, with a plateau at 900 mg twice daily. A decrease in tumor blood flow (Ktransand IAUC60) was observed with dynamic contrast-enhanced magnetic resonance imaging. Best tumor response was stable disease, observed in 50.9% of patients.ConclusionTelatinib was safe and well tolerated up to 1,500 mg twice daily. Based on pharmacodynamic and pharmacokinetic end points, telatinib 900 mg twice daily is the recommended dose for subsequent phase II studies.

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