A phase II study of sorafenib in combination with tegafur/uracil (UFT) for Asian patients with advanced hepatocellular carcinoma (HCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4589-4589
Author(s):  
Y. Shen ◽  
C. Hsu ◽  
C. Hsu ◽  
Z. Lin ◽  
P. Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Molar Ratio ◽  
Advanced Hepatocellular Carcinoma ◽  
Multikinase Inhibitor ◽  
Advanced Hcc ◽  
Asian Patients ◽  
Ecog Ps

4589 Background: Sorafenib, a multikinase inhibitor with antiangiogenic activity, has recently been approved for the treatment of unresectable HCC. Combination of sorafenib with metronomic chemotherapy has theoretic advantage in improving antitumor activity without increasing toxicities. UFT (tegafur: uracil = 4:1 in molar ratio), an oral fluoropyrimidine, is active in various gastrointestinal cancers. We conducted a phase II study to evaluate the efficacy and safety of sorafenib plus low-dose UFT in advanced HCC patients (pts). Methods: Pts with histologically or cytologically proven unresectable/metastatic HCC, ECOG PS 0–2, Child-Puch class A, platelets ≥ 100 K/μl, transaminases ≤ 5 × ULN, bilirubin ≤ 3 mg/dl, INR ≤ 2.3 and creatinine ≤ 1.5 × ULN were enrolled. Prior systemic therapy for advanced disease is not allowed. Sorafenib (400 mg bid) and UFT (125 mg/m2 based on tegafur bid) were taken per os continuously. Tumor assessment was performed q8w by RECIST criteria. Primary endpoint is progression-free survival (PFS). Results: Between April 2007 and April 2008, 53 pts were enrolled. Baseline pts characteristics were: M/F, 47/6; median age 57 (range, 31–83); CLIP score 0–3/4, 48/5; extrahepatic spread/macroscopic vascular invasion, 33/30; and HBsAg(+)/anti-HCV(+)/both(+), 38/13/4. 89% of pts were BCLC stage C. Pts received a median of 3.7 (range 0.3- 18.9+) months of treatment. There were 3 (6%) PR and 27 (51%) SD. The median PFS and OS were of 3.7 months (95% C.I., 1.9- 5.5) and 7.4 months (95% C.I., 3.4- 11.4), respectively. Adverse events (AEs) were summarized in Table . Hand-foot skin reaction (HFSR), fatigue, and diarrhea were most common AEs. HFSR was the major AE resulting in dose reduction (19%) or treatment delay (21%). Grade 3/4 neutropenia occurred in 2 pts (4%). Conclusions: Adding metronomic UFT chemotherapy to sorafenib may improve therapeutic efficacy of the latter in pts with advanced HCC. The toxicity profile of the combination is similar to that of sorafenib alone. [Table: see text] [Table: see text]

Phase II study of intrabuccally-administered amplitude-modulated electromagnetic fields in patients with advanced hepatocellular carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
F. P. Costa ◽  
A. C. de Oliveira ◽  
R. Meirelles ◽  
M. M. Machado ◽  
R. Surjan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Electromagnetic Fields ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Advanced Hcc ◽  
Independent Review

e15573 Background: Over the past few years we have identified tumor-specific frequencies for several common forms of cancer. The goal of this study was to assess the tolerability and effectiveness of electromagnetic fields amplitude-modulated at tumor-specific frequencies and administered by means of an intrabuccal spoon-shaped probe in patients with advanced hepatocellular carcinoma (HCC). Methods: From October 2005 to July 2007, patients with advanced HCC and Child-Pugh A or B were recruited in a phase II study. Three daily 60 min outpatient treatments were administered until disease progression or death. Imaging studies were performed every eight weeks. The primary efficacy end point was progression-free survival ≥ 6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: A total of 41 patients were enrolled, 17 had Child-Pugh A, 20 Child-Pugh B disease. The median age was 64.0 years. Seventeen patients (34.1%) were progression-free for more than 6 months. Median progression-free and overall survivals were 4.8 months (95% CI 2.3–6.0) and 6.9 months (95 CI 4.8–11.1). As of December 2008, four patients are alive and two patients, who are still undergoing therapy, remain progression-free for 30.4 and 30.7 months, respectively. Four patients had partial response (9.8%) and sixteen had stable disease for at least 12 weeks (39.0%) according to the RECIST criteria resulting in 48.8% disease control. All responses were confirmed by independent review. There were no NCI grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient grade 1 fatigue. Conclusions: In patients with advanced HCC and impaired hepatic function, treatment with amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of anti-tumor effects, which are long-lasting in some patients. No significant financial relationships to disclose.

Clinical, pharmacodynamic (PD), and pharmacokinetic (PK) evaluation of cediranib in advanced hepatocellular carcinoma (HCC): A phase II study (CTEP 7147).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4112-4112 ◽  
Author(s):  
Andrew X. Zhu ◽  
Marek Ancukiewicz ◽  
Jeffrey G. Supko ◽  
Lawrence Scott Blaszkowsky ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Steady State ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Vegf Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Eligibility Criteria ◽  
Advanced Hcc ◽  
Baseline Levels ◽  
Grade 3

4112 Background: Sorafenib remains the only approved systemic therapy in HCC. We performed a phase II study of cediranib (AZD2171)—a more potent and selective pan-VEGF receptor inhibitor—in advanced HCC patients (pts). Methods: Eligibility criteria included unresectable or metastatic measurable HCC, ECOG PS ≤2, CLIP score ≤3, and adequate organ function. Patients received cediranib at 30 mg po qd continuously (4-wk cycle). The primary endpoint was progression free survival (PFS). We also assessed overall survival (OS) and response rates, steady-state PK of cediranib, and blood circulating biomarkers. Results: Since 6/16/09, we have enrolled the targeted 17 pts required for the first stage of the planned study: ECOG 0/1/2=5/11/1, CLIP 1/2/3=6/4/7, Child A/B=14/3, BCLC C=17. Nine pts had prior sorafenib. The best response was stable disease in five pts (29%). The median PFS was 5.3 months (95% CI: 3.5-9.7). The median OS was 11.7 months (95% CI: 7.5-13.6). Grade 3 toxicities included hypertension (29%), hyponatremia (12%), elevated SGOT (12%) and one pt each (6%) in SGPT, fatigue, hyperbilirubinemia, cardiac ischemia, and proteinuria. Grade 4 pulmonary embolism and brainstem hemorrhage occurred in 1 pt each. Steady-state PK parameters (mean±SD) were, Cmin, 22±21 ng/mL; Cmax, 55±33 ng/mL; AUCτ, 887±503 ng*h/mL. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2 and Ang-2 decreased significantly after cediranib treatment (p<0.05). PFS was inversely correlated with baseline levels of bFGF, sVEGFR2 and VEGF, and OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-alpha and CD34+CD133+ hematopoietic progenitor cells (p<0.05). Conclusions: Cediranib at 30 mg daily is associated with high frequency of grade 3 hypertension and shows preliminary evidence of antitumor activity in advanced HCC pts. Exploratory studies confirmed potential PD and response biomarkers of anti-VEGF therapy. Cediranib exhibits similar PK in HCC pts as in those with other tumor types and normal/near normal hepatic function. This study was stopped by AstraZeneca after discontinuation of cediranib development for unrelated factors.

A multicenter phase II study of sorafenib, capecitabine, and oxaliplatin (SECOX) in patients with advanced hepatocellular carcinoma: Final results of Hong Kong-Singapore Hepatocellular Carcinoma Research Collaborative Group study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4117-4117 ◽  
Author(s):  
Thomas Cheung Yau ◽  
Foon Yiu Cheung ◽  
Francis Lee ◽  
Su Pin Choo ◽  
Hilda Wong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Asian Population ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Collaborative Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Grade One

4117 Background: This is a single arm, multi-center, phase II study to assess the efficacy and tolerability of sorafenib, oxaliplatin and capecitabine combination for the treatment of advanced hepatocellular carcinoma (HCC) patients. Methods: Eligible patients received SECOX regime—sorafenib 400 mg bid (Day one-fourteen), oxaliplatin 85 mg/m2 (Day one) and capecitabine 1700 mg/m2(Day one-seven) every two weeks. Response assessment was based on RECIST 1.0 criteria. The primary endpoint was time-to-progression (TTP) and the secondary endpoints were tumor response rate (RR), progression-free survival (PFS), overall survival (OS) and tolerability. Results: A total of 51 patients were enrolled in the trial.The median age was 58 years (range, 28-81) and 84% of patients were chronic hepatitis B carriers. Ninety percent of recruited patients belonged to BCLC stage C disease and 41 (80%) patients had extra-hepatic metastasis. The best RR was 16% and they were all partial response. Another 62% of patients achieved stable disease for at least eight weeks. The median TTP was 5.29 months (95% CI 3.81-5.88 months), PFS 5.26 months (95% CI 3.75-5.88 months) and OS was 11.73 months (95% CI 8.87- 15.38 months). Diarrhea (75%), Hand-foot-skin reaction (73%) and transient liver function derangement were the most commonly encountered adverse events, with the majority of patients having grade one or two. No treatment-related death was reported. Conclusions: The SECOX regime indicates preliminary promising activity and safety in Asian population with advanced HCC. Our data support a randomized trial comparing SECOX versus sorafenib alone for treatment of advanced HCC. Clinical trial information: NCT00752063.

Combination of capecitabine, oxaliplatin with bevacizumab in treatment of advanced hepatocellular carcinoma (HCC): A phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4574-4574 ◽  
Author(s):  
W. Sun ◽  
D. G. Haller ◽  
K. Mykulowycz ◽  
M. Rosen ◽  
M. Soulen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Female Ratio ◽  
Advanced Hcc ◽  
Standard Chemotherapy Regimen ◽  
Hand Foot Syndrome ◽  
Number Of Treatment

4574 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers globally and its incidence of in USA is increasing. Unfortunately, most patients with HCC are unsuitable for surgical resection or transplantation. Because of the heterogeneity of this disease and poor liver function in many patients, there is no generally accepted standard chemotherapy regimen for HCC. Efforts have been made to investigate effective and tolerable therapy for patients with advanced HCC. We conducted a phase II study to evaluate the efficacy and feasibility of the combination of bevacizumab, oxaliplatin and capecitabine in patients with advanced or metastatic HCC. The primary goal of the study was to evaluate the progression-free survival rate. The secondary endpoints include response, overall survival and toxicity. Methods: Patients with advanced or unresectable untransplantable metastatic HCC who had adequate bone marrow, liver and renal function (ANC ≥ 1,500/mm3, platelets ≥ 75,000/mm3, serum creatinine ≤ 2.0 mg/dl, total bilirubin ≤ 3.0 mg/dl, transaminases ≤ 5 upper limit of normal, and INR ≤ 1.5) were eligible to the study. Bevacizumab (5 mg/kg) and oxaliplatin (130 mg/m2) were administered intravenously day 1 of each 21- day cycle. Capecitabine (825 mg/m2, twice a day) was administered days 1 to 14. Results: Thirty patients (male/female ratio of 23/7) have been enrolled, with a median age of 57 (range 23–85). The average number of treatment cycles was 8 (2–25 cycles). Of evaluable patients, 3 patients (11%) achieved partial response, 21 patients had stable disease (78%) with a disease control rate of 89%. The mean PFS was 5.4 months with 3- and 6- months PFS of 70%, and 40%. There were 33% Gr. 2/3 oxaliplatin-related peripheral neuropathy and 11 % capecitabine-related Gr. 2/3 hand- foot syndrome. One patient had gastrointestinal perforation and sepsis after his first administration of bevacizumab and oxaliplatin. Two patients had esophageal varices-related bleeding, likely disease-related. Conclusions: The results demonstrate that the combination of bevacizumab, oxaliplatin and capecitabine is effective and tolerable in treatment of advanced HCC and should be considered for the further investigation. [Table: see text]

scholarly journals Efficacy, Safety, and Potential Biomarkers of Sunitinib Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study

2009 ◽  
Vol 27 (18) ◽  
pp. 3027-3035 ◽  
Author(s):  
Andrew X. Zhu ◽  
Dushyant V. Sahani ◽  
Dan G. Duda ◽  
Emmanuelle di Tomaso ◽  
Marek Ancukiewicz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Sunitinib Treatment

PurposeTo assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response.Patients and MethodsWe conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functional magnetic resonance imaging to evaluate vascular changes in HCC after sunitinib treatment. Circulating molecular and cellular biomarkers were evaluated before and at six time points after sunitinib treatment.ResultsThirty-four patients were enrolled. The objective response rate was 2.9%, and 50% of patients had stable disease. Median PFS was 3.9 months (95% CI, 2.6 to 6.9 months), and overall survival was 9.8 months (95% CI, 7.4 months to not available). Grade 3 or 4 toxicities included leukopenia/neutropenia, thrombocytopenia, elevation of aminotransferases, and fatigue. Sunitinib rapidly decreased vessel leakiness, and this effect was more pronounced in patients with delayed progression. When evaluated early (at baseline and day 14) as well as over three cycles of treatment, higher levels of inflammatory molecules (eg, interleukin-6, stromal-derived factor 1α, soluble c-KIT) and circulating progenitor cells were associated with a poor outcome.ConclusionSunitinib shows evidence of modest antitumor activity in advanced HCC with manageable adverse effects. Rapid changes in tumor vascular permeability and circulating inflammatory biomarkers are potential determinants of response and resistance to sunitinib in HCC. Our study suggests that control of inflammation might be critical for improving treatment outcome in advanced HCC.

scholarly journals Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study

Oncology ◽  
2013 ◽  
Vol 85 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Chih-Hung Hsu ◽  
Yoon Koo Kang ◽  
Tsai-Shen Yang ◽  
Chia-Tung Shun ◽  
Yu-Yun Shao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
First Line Therapy ◽  
Asian Patients ◽  
Multicenter Phase ◽  
Line Therapy

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Final results of phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in metastatic colorectal cancer (mCRC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 574-574 ◽  
Author(s):  
Kentaro Yamazaki ◽  
Tomohiro Nishina ◽  
Takeshi Kato ◽  
Takayuki Yoshino ◽  
Yoshinori Miyata ◽  
...  
Keyword(s):  
Survival Rate ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Present Report ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Target Lesion ◽  
Ecog Ps ◽  
The Impact

574 Background: The SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) demonstrated a promising activity with tolerated toxicities compared to mFOLFOX6 in a randomized phase II study for mCRC. We previously reported the promising results of a phase II study of SOL+BV in Gastrointestinal Cancers Symposium 2012 (Kato T, et al.) focusing on early clinical outcomes, overall response rate (ORR), progression free survival (PFS) and safety. The final follow-up (cut-off date Dec 2012) has been completed, and we report up-dated overall survival (OS) and the impact of early objective tumor response (EOTR) on OS in the present report. Methods: The main inclusion criteria were; (1) metastatic colorectal adenocarcinoma, (2) age ≥20 years, (3) no prior chemotherapy, (4) target lesion (RECIST v1.0), (5) ECOG PS 0-1, 6) written informed consent. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week. Oxaliplatin (85 mg/m2) and BV (5 mg/kg) were administered on day 1. This treatment was repeated every 2 weeks. The primary endpoint was ORR confirmed by the independent review committee according to RECIST v1.0. This trial was supported by Taiho Pharmaceutical CO, LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881). Results: From Oct 2009 to Apr 2010, 31 pts were enrolled. Of the eligible 29 pts, median age was 62; PS 0/1 was 24/5; number of metastatic organs 1/≥2 was 15/14. ORR was 86% (95%CI, 68-96), and the median PFS was 15 months (95%CI, 10-26). OS has not reached median with a median follow-up time of 34 months. Two-year survival rate was 72%. EOTR (RECIST sum ≥30% shrinkage) at 6-weeks was observed in 35% of pts. Two-year survival rate in these pts with an EOTR at 6-weeks was 80%, while in other pts without an EOTR at 6-weeks was 68%. The curative resection rate of metastatic lesions was 28%. The incidence (≥10%) of grade 3/4 adverse drug reactions were; neutropenia 20%, hypertension 23%, anorexia 20%, fatigue 17%, diarrhea 10%, and sensory neuropathy 53%. Conclusions: The SOL+BV regimen showed the promising activity for mCRC. The high proportion of EOTR might lead to long survival. Further evaluation of this regimen would be warranted. Clinical trial information: 090881.

Phase Ib trial of tepotinib in Asian patients with advanced hepatocellular carcinoma (HCC): Final data including long-term outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4087-4087 ◽  
Author(s):  
Shukui Qin ◽  
Tae-You Kim ◽  
Ho Yeong Lim ◽  
Baek-Yeol Ryoo ◽  
Jürgen Scheele ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Progression Free Survival ◽  
Response Duration ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Advanced Hepatocellular Carcinoma ◽  
Modest Improvement ◽  
Phase Ib ◽  
Advanced Hcc ◽  
Ecog Ps

4087 Background: The incidence of hepatocellular carcinoma (HCC), a leading cause of cancer death, is increasing with the increasing incidence of chronic liver disease. Sorafenib, the only approved systemic therapy for advanced HCC, provides modest improvement in overall survival. Preclinical studies suggest c-Met is a valid target in HCC, but non-selective TKIs with c-Met inhibitory activity have not shown efficacy in trials, possibly due to lack of c-Met inhibition. Tepotinib (MSC2156119J) is a highly selective c-Met inhibitor that has favorable safety and promising activity, particularly against c-Met+ solid tumors. We report the final results of a phase Ib trial of tepotinib in patients (pts) with advanced HCC. Methods: Pts were Asian adults with confirmed HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG PS 0–2. Pts received tepotinib 300, 500 (the RP2D) or 1,000 mg/day on a 21-day cycle. c-Met expression status was retrospectively determined by IHC. Results: 27 pts were enrolled (median age 57 [38-69]; male 23; ECOG PS 0/1 11/16); 7 received tepotinib 300 mg/day, 14 500 mg/day, and 6 1,000 mg/day (3 with dose reduction). No DLTs were observed. 22 pts experienced treatment-related treatment-emergent adverse events (TRTEAEs), most commonly diarrhea (n = 10), nausea (8), elevated AST (7), and elevated ALT (6). 9 pts had grade ≥3 TRTEAEs, including elevated AST (3) and elevated ALT (3). Best overall response (BOR) was partial response (PR) in 2 pts, one of whom received tepotinib 500 mg (response duration 16.1 months) and one 1,000 mg (4.4 months); both had c-Met+ tumors. A further 8 pts had a BOR of stable disease (SD), 1 pt non-complete response (CR)/non-progressive disease (PD), and 14 pts had PD (2 pts not evaluable). Five pts had progression free survival > 8 months. PK were as expected from previous studies. Conclusions: Tepotinib at doses of up to 1,000 mg/day was well tolerated by Asian pts with advanced HCC and a maximum tolerated dose was not reached. Antitumor activity was observed, particularly in pts with c-Met+ tumors. The ongoing phase II part of this study is comparing the efficacy and safety of first-line tepotinib and sorafenib in pts with c-Met+ HCC. Clinical trial information: NCT01988493.

Phase II study of ipilimumab and nivolumab (ipi/nivo) in metastatic uveal melanoma (UM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9522-9522 ◽  
Author(s):  
Meredith Pelster ◽  
Stephen K. Gruschkus ◽  
Roland Bassett ◽  
Dan S. Gombos ◽  
Michael Shephard ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Duration Of Treatment ◽  
Safety And Efficacy ◽  
One Year ◽  
Ecog Ps

9522 Background: UM is the most common primary intraocular malignant tumor in adults. Approximately 40-50% of patients (pts) with UM will ultimately develop metastatic disease. There is currently no standard approach for metastatic UM. Early studies of single agent immunotherapy (IO) in metastatic UM have yielded meager results. Combination checkpoint inhibitor IO has the potential to improve response rates and survival. Herein, we report the safety and efficacy of ipi/nivo in metastatic UM. Methods: We performed a single-arm phase II study in metastatic UM (CA184-187) for pts with at least 1 measureable lesion and ECOG PS 0-1. Any number of prior treatments were permitted. Pts received nivolumab 1mg/kg IV plus ipilimumab 3mg/kg IV every 3 weeks for a total of 4 doses; maintenance nivolumab was dosed 3mg/kg every 2 weeks or 480mg IV every 4 weeks. The primary efficacy endpoint was best overall response rate (BORR) as determined by irRC. Secondary endpoints were median progression free survival (PFS), median overall survival (OS), and one-year OS. Results: As of the January 31, 2019 data cutoff, 39 pts were enrolled. 35 pts received at least one treatment and were evaluable for toxicity. 5 pts were inevaluable for response due to lack of follow-up imaging, leaving 30 pts evaluable for efficacy. 32 pts (91%) experienced any adverse event (AE), and 29 pts (83%) experienced any treatment related AE (TRAE). Grade 3-4 TRAEs occurred in 14 pts (40%). 10 pts (29%) were removed from the study due to AEs. There were no treatment-related deaths. Median duration of follow up is 60.5 weeks. 19 pts (63%) completed all 4 cycles of ipi/nivo; median duration of treatment was 16 weeks. The BORR was partial response for 5 pts (17%), stable disease (SD) for 16 pts (53%), and progression of disease for 9 pts (30%). 8 pts had SD for at least 6 months. Median PFS was 26 weeks. Median OS was 83 weeks (1.6 years), and one-year OS was 62%. Conclusions: Full results of ipi/nivo safety and efficacy including immune-related AE and clinical characteristics of the responders will be presented at the meeting. Preliminary translational tumor work including RNA analysis has been performed on a subset of responders. Clinical trial information: NCT01585194.

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