A randomized phase II, open-label trial of orally administered SAR302503 in patients with polycythemia vera (PV) or essential thrombocythemia (ET) who are resistant or intolerant to hydroxyurea.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS6641-TPS6641 ◽  
Author(s):  
Ayalew Tefferi ◽  
Jorge E. Cortes ◽  
Andreas Hochhaus ◽  
Jean-Jacques Kiladjian ◽  
Ruben A. Mesa ◽  
...  
Keyword(s):  
Phase 1 ◽  
Symptom Burden ◽  
Primary Myelofibrosis ◽  
Open Label ◽  
Eligibility Criteria ◽  
Allele Burden ◽  
Phase 2 Trial ◽  
Stat3 Phosphorylation ◽  
Ecog Ps ◽  
Jak2v617f Allele Burden

TPS6641 Background: Hydroxyurea is widely used to treat patients with high-risk PV and ET. However, some patients are either clinically resistant to hydroxyurea or have unacceptable side effects, supporting the need for active therapeutic options in this setting. SAR302503 is an orally administered selective JAK-2 inhibitor that reduced symptom burden and provided a durable clinical benefit, including a reduction in the JAK2V617F allele burden, with an acceptable safety profile in a Phase 1/2 trial of patients with primary myelofibrosis (MF), post-PV MF, or post-ET MF (J Clin Oncol 2011;29:789; Pardanani, ASH 2011; Abs 3838). Based on the results in MF, in October 2011 we initiated a Phase 2 trial to evaluate SAR302503 for the treatment of patients with PV and ET who are resistant or intolerant to hydroxyurea (NCT01420783; ARD12042). Methods: Eligibility criteria include age of at least 18 years, ECOG PS 0–2, and hydroxyurea resistant PV or ET as defined by European LeukemiaNet Consensus Criteria (Blood 2009;113:4829). Patients are being randomized (1:1:1) to receive 100, 200, or 400 mg of SAR302503 orally once daily in consecutive 28-day cycles for at least 8 cycles in the absence of progression or unacceptable toxicity. The primary end points will be assessed after the completion of 8 cycles and are: for PV, the proportion of patients maintaining a hematocrit below 45% without phlebotomy for at least 3 months; for ET, the proportion of patients with a platelet count lower than 400 × 109/L for at least 3 months. Secondary objectives include safety, response rate, pharmacokinetics, pharmacodynamics as measured by JAK2V617F allele burden and STAT3 phosphorylation inhibition, assessment of disease-related symptoms, and quality of life. Enrollment of the planned total of 90 patients is ongoing at approximately 45 sites globally. Twelve patients have been enrolled as of January 2012.

JAKARTA: A phase III, multicenter, randomized, double-blind, placebo-controlled, three-arm study of SAR302503 in patients with intermediate-2 or high-risk primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF with splenomegaly.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS6639-TPS6639 ◽  
Author(s):  
Animesh Dev Pardanani ◽  
Jorge E. Cortes ◽  
Francisco Cervantes ◽  
Claire N Harrison ◽  
Francesco Passamonti ◽  
...  
Keyword(s):  
Phase 1 ◽  
Primary Myelofibrosis ◽  
Phase Iii ◽  
Open Label ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Allele Burden ◽  
Open Label Extension ◽  
Symptom Response ◽  
Ecog Ps

TPS6639 Background: SAR302503 is an orally administered selective JAK-2 inhibitor being evaluated for the treatment of MF. In a phase 1 study, SAR302503 reduced spleen size and disease-related symptoms and provided clinical benefit, including a reduction in the JAK2V617F allele burden, with an acceptable safety profile in patients with primary MF, post-PV MF, or post-ET MF (J Clin Oncol 2011;29:789). An ongoing open-label extension of this trial confirmed the durability of those results and found that doses between 400–500 mg/day of SAR302503 represented the optimal balance between safety and efficacy (Pardanani, ASH 2011;Abs 3838). These results led us to initiate a Phase 3 trial in December 2011 to evaluate SAR302503 at doses of 400 mg/day and 500 mg/day, compared with placebo, for the treatment of patients with MF (NCT01437787; EFC12153). Methods: Eligibility criteria include age of at least 18 years, platelets >50,000/µl, ECOG PS 0–2, and a diagnosis of high- or intermediate-risk 2 primary MF, post-PV MF, or post-ET MF according to IPSS criteria (Blood 2009;113:2895). Patients are being randomized (1:1:1) to receive 400 mg or 500 mg of SAR302503 or placebo orally once a day for at least 6 consecutive 28-day cycles. Assigned treatment will continue as long as patients are deriving benefit or until progression or unacceptable toxicity. Cross-over is allowed after 6 cycles or in case of progression before completion of 6 cycles according to predefined criteria. The primary endpoint is spleen response (≥35% reduction in spleen volume by MRI/CT at the end of cycle 6). Key secondary objectives are symptom response rate and durability of spleen response. Additional secondary endpoints include assessment of allele burden and bone marrow fibrosis reduction. It is planned to randomize 75 patients per treatment group at approximately 130 sites worldwide.

International multicenter phase II study of the HDAC inhibitor (HDACi) depsipeptide (FK228) in cutaneous T-cell lymphoma (CTCL): Interim report

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3063-3063 ◽  
Author(s):  
S. Whittaker ◽  
W. McCulloch ◽  
T. Robak ◽  
E. Baran
Keyword(s):  
T Cell ◽  
Clinical Activity ◽  
Open Label ◽  
Eligibility Criteria ◽  
Cell Counts ◽  
T Cell Lymphomas ◽  
The Uk ◽  
Ecog Ps

3063 Background: Depsipeptide, a unique bicyclic peptide histone deacetylase inhibitor (HDACi), has shown activity in a range of in vitro and in vivo tumor models and clinical activity in T-cell lymphomas and prostate cancer. This study seeks to confirm the CTCL activity previously reported by the NCI (Piekarz, et al., ASCO, 2004). Methods: Single-arm, open label study, in 25 centers in the UK, Germany, Poland and the US. Patients aged ≥18 years with biopsy-confirmed CTCL (centrally reviewed) who have failed at least one prior systemic treatment receive up to 6 cycles of depsipeptide as a 4-hour IV infusion on Days 1, 8 and 15 q 28 days. Eligibility criteria include: mycosis fungoides and Sézary syndrome plus variants, Stages IB - IVA, adequate organ function, ECOG PS ≤ 1. Patients with significant cardiovascular abnormalities are excluded in addition to those taking QTc-prolonging or CYP3A4-inhibiting drugs. The primary endpoint is overall reponse rate measured by a combination of imaging, circulating cell counts and a weighted skin average instrument, confirmed by standardized photography. A subset undergoes pharmacokinetic assessments. Correlative studies include acetylation status, apoptotic markers and proteomic analyses where possible. Target accrual is 76 to yield 64 evaluable patients. Results: 30 patients have received treatment with 17 evaluable for efficacy. Responses seen are 1 cCR, 4 PRs (duration 2+ to 6 months) 9 SD and 3 PD. 3 patients withdrew early for PD and 2 for other reasons. The remaining patients on study are too early to assess. Most frequent toxicities are: nausea/vomiting, fatigue, myelosuppression and asymptomatic ECG changes. No patient has withdrawn for toxicity and there have been no treatment-related deaths. Conclusions: The previously reported efficacy of depsipeptide in CTCL has also been seen in the present study. Duration of response is encouraging. Toxicity is manageable and the study continues to accrue. [Table: see text]

ABT-869 in non-small cell lung cancer (NSCLC): Interim results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8074-8074
Author(s):  
E. Tan ◽  
R. Salgia ◽  
B. Besse ◽  
G. Goss ◽  
D. R. Gandara ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Specific Inhibitor ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Trial

8074 Background: ABT-869 is a novel orally active, potent and specific inhibitor of vascular endothelial growth factor and platelet derived growth factor receptor tyrosine kinases. Methods: This ongoing, open-label, randomized, multicenter phase 2 trial of ABT-869 at 0.10 mg/kg daily (Arm A) and 0.25 mg/kg daily (Arm B) until progressive disease (PD) or intolerable toxicity, was initiated to assess antitumor activity and toxicity of ABT-869 in patients (pts) with NSCLC. Eligibility criteria included locally advanced or metastatic NSCLC; ≥ 1 prior systemic treatment, and ≥1 measurable lesion by RECIST criteria. The primary endpoint was the progression free (PF) rate at 16 wks. Secondary endpoints were objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed by the investigator and centrally; central assessment results are provided. Results: 138 patients (pts) were enrolled from 08/07–10/08 from 27 centers with interim data available for 94 pts (Arm A, n=43; Arm B; n=51). Median age was 64 years and 62 years in Arm A and B respectively. For the interim analysis population (Arm A, n=24; Arm B, n=24), 16 (33.3%) pts were PF at 16 wks: 7 (29.2%) in Arm A and 9 (37.5%) in Arm B. The ORR in Arm A (n=30) was 0% and 7.3% in Arm B (n=41). The median TTP and median PFS were 110 and 109 days, and 112 days and 108 days in Arm A and B, respectively. The most common adverse events (AEs) in Arm A were fatigue (35%), nausea (21%), and anorexia (21%), and in Arm B were hypertension (51%), fatigue (51%), diarrhea (43%), anorexia (41%), nausea (31%), proteinuria (31%) and vomiting (26%). The most common grade 3/4 toxicities in the Arm A were fatigue (7%), ascites (5%), dehydration (5%), pleural effusion (5%), and in the Arm B were hypertension (23%), fatigue (8%), PPE syndrome (8%), dyspnoea (6%) and stomatitis (6%). Most AE's were mild/moderate and reversible with interruptions/dose reduction/or discontinuation of ABT-869. Conclusions: ABT-869 demonstrates an acceptable safety profile and appears to be active in NSCLC patients. [Table: see text]

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

The combination of bevacizumab (B) and erlotinib (E) shows significant biological activity in patients with advanced hepatocellular carcinoma (HCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4567-4567 ◽  
Author(s):  
M. B. Thomas ◽  
R. Chadha ◽  
M. Iwasaki ◽  
K. Glover ◽  
J. L. Abbruzzese
Keyword(s):  
Growth Factor ◽  
Systemic Therapy ◽  
Early Death ◽  
Vascular Tumors ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Tumor Vascularity ◽  
Eligibility Criteria ◽  
Best Response ◽  
Ecog Ps

4567 Purpose: HCC is the 5th most common solid tumor worldwide and the incidence is rising in western countries. >75% of patients (pts) have advanced disease and are ineligible for surgical or loco-regional therapies. Existing cytotoxic chemotherapy does not prolong pt survival and can have significant toxicity in cirrhotic pts. HCC are highly vascular tumors, and based on the prevalence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptors (EGFR) in HCC, we are conducting a phase II, single-arm, open-label trial of B and E in pts with HCC. Patients and Methods: Eligibility criteria include biopsy-proven unresectable HCC, Child- Pugh class A or B cirrhosis, bilirubin = 2.0 mg/dL, transaminases (TA)= 5 x ULN, Plts = 50,000 K/UL and ECOG PS = 2. Prior allowed therapies are surgery, external radiotherapy, ablation, chemoembolization (TACE) and one systemic therapy. Pts receive B 10 mg/kg q14 days plus E 150 mg orally daily until PD or unacceptable toxicity. Results: The primary endpoint is the percent of pts alive and progression free (PFS) after 16 wks of therapy based on median PFS of 3–5 mos in published studies. Response is evaluated by RECIST. 29 pts have been enrolled. For all pts, the med. age was 61 (29–77), 24 (82.8%) were male, 19 (65.5%) were Caucasian; ECOG PS 0, 11 pts, PS 1, 18 pts; 6 had prior systemic therapy, and 10 pts had prior TACE. Of the 27 pts evaluable for response, 1 pt confirmed CR, 5 pts PRs (4 confirmed) (22% RR; 5/6 pts 1st line) 9 pts SD at 16 wks (55% PFS 16 wks); 5 additional pts SD at 8 wks (74% disease control rate). 2 pts PD at 16 wks, 1 pt PD at 8 wks, 2 removed for toxicity (proteinuria, fatigue); 1 early death. 12/14 pts with SD as their best response showed minor tumor shrinkage, decreased tumor vascularity or increased necrosis. Generally B+E are well tolerated; Gr 3–4 toxicities were TA elevation, hyperkalemia, acne (1 pt each), diarrhea, proteinuria (2 pts), GI bleed (3 pts), fatigue (4 pts), hypertension (5 pts). Conclusions: Based on these early encouraging results and favorable toxicity profile, the combination of B + E appears to have significant clinically meaningful biologic activity in HCC. The trial will continue to full accrual of 40 patients. The combination of B + E warrants further study in HCC. No significant financial relationships to disclose.

A phase II study of ABT-869 in hepatocellular carcinoma (HCC): Interim analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4581-4581 ◽  
Author(s):  
H. Toh ◽  
P. Chen ◽  
B. I. Carr ◽  
J. J. Knox ◽  
S. Gill ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ct Scan ◽  
Phase Ii ◽  
Tyrosine Kinases ◽  
Interim Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Trial

4581 Background: ABT-869 is a novel orally active, potent and selective inhibitor of the vascular endothelial growth factor and platelet derived growth factor families of receptor tyrosine kinases. Results of an interim analysis of a phase 2 trial of ABT-869 in HCC are presented. Methods: An open-label, multicenter phase II trial (M06–879) of oral ABT-869 at 0.25 mg/kg daily in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity, is ongoing. Key eligibility criteria included unresectable or metastatic HCC; up to one prior line of systemic treatment; and at least one measurable lesion by computed tomography (CT) scan. The primary endpoint was the progression free (PF) rate at 16 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed centrally and by the investigators; presented results are from central assessment. Results: 44 pts were enrolled from 09/07 to 08/08 at 6 centers internationally, with interim data available for 34 pts. There were 28 C-PA pts (median age, 63.5 y [range, 20- 81]) and 6 C-PB pts (median age, 64.5 y [range, 36–69]) and 73.5% received no prior systemic therapy. For the 19 evaluable C-PA pts included in the per-protocol interim analysis, 8 (42.1%) were progression free at 16 weeks [95% CI 20.3, 66.5]. The estimated ORR was 8.7% [95% CI, 1.1, 28] for the 23 C-PA pts and 0% for the 2 C-PB pts who had at least one post-baseline CT scan reviewed by central imaging. For all 34 pts, median TTP was 112 d [95% CI, 110, -], median PFS was 112 d [95% CI, 61, 168] and median OS was 295 d [95% CI, 182, 333]. The most common adverse events (AEs) for all pts were hypertension (41%), fatigue (47%), diarrhea (38%), rash (35%), proteinuria (24%), vomiting (24%), cough (24%) and oedema peripheral (24%). The most common grade 3/4 AEs for all pts were hypertension (20.6%) and fatigue (11.8%). Most AEs were mild/moderate and reversible with interruption/dose reductions/or discontinuation of ABT-869. Conclusions: ABT-869 appears to benefit HCC patients, with an estimated TTP of 112 days and an acceptable safety profile. Updated results from this ongoing study will be presented. [Table: see text]

Reductions in JAK2V617F allele burden with ruxolitinib treatment in COMFORT-II, a phase III study comparing the safety and efficacy of ruxolitinib to best available therapy (BAT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6514-6514 ◽  
Author(s):  
Alessandro M. Vannucchi ◽  
Jean-Jacques Kiladjian ◽  
Heinz Gisslinger ◽  
Francesco Passamonti ◽  
Haifa Kathrin Al-Ali ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Phase Iii ◽  
Total Daily Dose ◽  
Molecular Response ◽  
Open Label ◽  
Phase 3 ◽  
Allele Burden ◽  
Open Label Phase ◽  
Allele Specific ◽  
Jak2v617f Allele Burden

6514^ Background: Ruxolitinib is a potent and selective JAK1/2 inhibitor approved for the treatment of myelofibrosis (MF) based on results of the phase 3 COMFORT studies. Ruxolitinib demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life of patients (pts) with MF. Since one measure of efficacy is molecular response, this analysis correlates changes in mutant allele burden (%V617F) with spleen size reduction in COMFORT-II. Methods: COMFORT-II is a randomized, open-label, phase 3 study comparing ruxolitinib 15 or 20 mg twice daily (BID) with BAT. The primary endpoint was a ≥ 35% reduction in spleen volume from baseline (BL) at week 48. Change in %V617F was measured by allele specific qPCR. Pts were stratified by reduction in %V617F (< 10%, 10-20%, > 20%) and results were correlated with achievement of the primary endpoint. Results: More pts in the ruxolitinib arm had ≥ 10% V617F reductions compared with BAT (41% vs 5%; P = .01; Table). The majority of reductions > 20% were gradual and progressive over the course of the study; 2 pts had rapid reductions from 48% to 1% and 45% to 9% over 48 weeks. In the ruxolitinib arm, significantly more pts with a > 20% V617F reduction achieved the primary endpoint compared with pts with a < 10% reduction (79% vs 30%; P = .004); in each group, gender did not affect spleen response. For pts with < 10% reductions (15 mg BID, n = 16; 20 mg BID, n = 24), the average total daily dose (TDD) was ruxolitinib 29.6 mg; pts with > 20% reductions (15 mg BID, n = 3; 20 mg BID, n = 11) had a TDD of 35.3 mg. Conclusions: Pts who received ruxolitinib had larger reductions in JAK2V617F allele burden compared with BAT. %V617F reductions were gradual over the course of the 48-week study; longer follow-up is needed to determine the extent of allele burden reduction. [Table: see text]

Safety, tolerability, and pharmacokinetics (PK) of rilotumumab in Japanese patients (pts) with advanced solid tumors.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 130-130
Author(s):  
Toshihiko Doi ◽  
Rui Tang ◽  
Yilong Zhang ◽  
Elwyn Loh ◽  
Richard Lizambri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Solid Tumors ◽  
Phase 1 ◽  
Human Monoclonal Antibody ◽  
Locally Advanced ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Open Label ◽  
Eligibility Criteria ◽  
Dose Escalation Study

130 Background: Rilotumumab (R) is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor, the only known MET receptor ligand. The MET pathway has been identified as a potentially useful target for therapeutic blockade in oncology. R has been studied in multiple phase 2 trials either as monotherapy or combination therapy, including a phase 2 trial in gastric cancer combining R with epirubicin, cisplatin, and capecitabine. A phase 1 study was done to evaluate the safety, tolerability, and PK of R in Japanese pts. Methods: An open-label, dose-escalation study was performed with R at 10 mg/kg (Cohort 1A), escalating to 20 mg/kg (Cohort 1B) if no dose-limiting toxicities (DLTs) were observed. Key eligibility criteria were Japanese pts with unresectable locally advanced or metastatic carcinoma, age ≥ 20 yr, ECOG ≤ 1, and refractory to standard treatment (tx). Pts received R as an intravenous infusion on days 1 and 15 of each 28-day cycle, except for cycle 1 in which the day 15 dose was skipped to facilitate PK analysis. DLTs were evaluated in cycle 1. Results: A total of 9 pts were enrolled (1A, n = 3; 1B, n = 6). No DLTs were noted. As of 17 April 13, tx-emergent AEs were reported in 89% of pts. Tx-emergent AEs occurring in > 1 pt overall were vomiting (33%), diarrhea (22%), decreased hemoglobin (22%), hypoalbuminemia (22%), and nausea (22%). One grade 3 tx-emergent AE was observed (decreased hemoglobin; 10 mg/kg). Tx-related AEs were reported in 56% of pts. One grade ≥ 2 tx-related AE was observed (hypoalbuminemia; 20 mg/kg). 8 pts discontinued R due to disease progression; 1 pt remained on the investigational product. Mean exposure of R (Cmax and AUC) appeared to be doubled as dose increased from 10 to 20 mg/kg. The estimated mean CL was approximately 0.2 mL/hr/kg in both cohorts, suggesting a linear PK from 10 to 20 mg/kg. The terminal half-life of R was about 15 days. Conclusions: R monotherapy had an acceptable safety profile in Japanese pts with advanced solid tumors. These phase 1 safety and PK data support the further evaluation of R combined with chemotherapy in Japanese pts with MET-positive metastatic gastric cancer. Clinical trial information: NCT01791374.

ARQ 087, an oral pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients (pts) with advanced intrahepatic cholangiocarcinoma (iCCA) with FGFR2 genetic aberrations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4017-4017 ◽  
Author(s):  
Vincenzo Mazzaferro ◽  
Bassel F. El-Rayes ◽  
Christian Cotsoglou ◽  
William Proctor Harris ◽  
Nevena Damjanov ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Phase 1 ◽  
Treatment Options ◽  
Plasma Concentrations ◽  
Moderate Intensity ◽  
White Female ◽  
Open Label ◽  
Genetic Aberrations ◽  
Tumor Reduction ◽  
Ecog Ps

4017 Background: FGFR genetic aberrations have been implicated in the development and progression of a number of solid tumor types, including iCCA. Pts with unresectable advanced iCCA who relapse after first-line chemotherapy have limited treatment options with poor prognosis. Recently, FGFR2 fusions, observed in up to 20% of pts, have been recognized as a potential therapeutic target. ARQ 087 is a multi-kinase inhibitor with a potent pan-FGFR activity. Methods: 119 cancer pts were enrolled in the phase 1/2, open-label study of ARQ 087. Study design and results of the phase 1were reported previously. Assessments included response by RECIST v1.1 every 8 wks, safety (physical examination, vital signs, ECOG PS, laboratory tests), plasma concentrations of phosphate and FGF19, 21 and 23 (potential biomarkers). Results: As of 1Feb17, 35 iCCA pts with FGFR2 genetic aberrations were treated with ARQ 087 300 (n = 33) or 400 mg (n = 2) daily. FGFR2 status was identified by FISH or NGS, 29/35 pts were FGFR2 fusion positive (FISH n = 15/18; NGS n = 14/17). Pts were all white, female (60%) with ECOG PS 0 (69%) and median age 58 yrs (31-82). Median number of prior systemic therapies was 1(0-6). Drug-related AEs (all grades) were reported in 89% of pts; the most common (≥10%) included nausea (37%), dry mouth (29%), asthenia (26%), fatigue, vomiting (23%, each), abnormal LFTs, dysgeusia (20%, each), alopecia, diarrhea, vision blurred (14%, each), and conjunctivitis (11%). Grade 3/4 AEs occurring in ≥2 pts were asthenia and abnormal LFTs (6%, each). AEs were mostly (71%) of mild to moderate intensity, manageable and reversible. Median time on treatment was 183 days (95%CI: 166-289). 19 pts were on treatment for > 16 wks, nine are ongoing. 30 pts had at least one post-treatment radiographic assessment: 6 (20%) had PR (32-47% tumor reduction, all FGFR2 fusion positive), 17 SD (7 had tumor reduction between 10 to 25%), and 7 had PD. One pt died prior to scheduled assessment and assessment in 4 pts is pending. Conclusions: ARQ 087 demonstrated encouraging antitumor activity and manageable safety profile. Updated data, including safety, efficacy and biomarkers will be presented. Clinical trial information: NCT01752920.

Sign in / Sign up

Export Citation Format

Share Document