Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
David Cunningham ◽  
Niall C. Tebbutt ◽  
Irina Davidenko ◽  
André M. Murad ◽  
Salah-Eddin Al-Batran ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Gastroesophageal Junction ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
First Line Therapy ◽  
Line Therapy

KEYNOTE-062: Phase III study of pembrolizumab (MK-3475) alone or in combination with chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS185-TPS185 ◽  
Author(s):  
Josep Tabernero ◽  
Yung-Jue Bang ◽  
Charles S. Fuchs ◽  
Atsushi Ohtsu ◽  
Uma Kher ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Phase Iii ◽  
Primary Study ◽  
First Line ◽  
Open Label ◽  
Double Blind ◽  
End Points ◽  
First Line Therapy ◽  
Line Therapy

TPS185 Background: Pembrolizumab (pembro) is a monoclonal antibody against PD-1 designed to block its interaction with PD-L1 and PD-L2 and permit an antitumor immune response. In KEYNOTE-012, pembro showed a 22% ORR (RECIST v1.1, central review) and a manageable safety profile in patients (pts) with advanced gastric cancer. The randomized, phase 3 KEYNOTE-062 study (NCT02494583) is designed to compare the efficacy and safety of pembro alone or in combination with cisplatin + a fluoropyrimidine with those of cisplatin + a fluoropyrimidine as first-line therapy for PD-L1+/HER2– advanced gastric or GEJ adenocarcinoma. Methods: Key eligibility criteria include age ≥ 18 y, locally advanced or metastatic PD-L1+/HER2– gastric or GEJ adenocarcinoma, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for advanced disease. Pts are randomized 1:1:1 to pembro 200 mg Q3W (arm 1), pembro + cisplatin 80 mg/m2 Q3W + 5-fluorouracil (5-FU) 800 mg/m2 on days 1-5 of each Q3W cycle (arm 2), or placebo Q3W + cisplatin + 5-FU (arm 3); 5-FU may be replaced with capecitabine 1000 mg/m2 twice daily on days 1-14 of each cycle. Randomization is stratified by region (Europe/North America/Australia vs Asia vs rest of world), disease status (locally advanced vs metastatic), and chosen fluoropyrimidine (5-FU vs capecitabine). Arm 1 is open label; in arms 2 and 3, assignment to pembro vs placebo is double blind. In all arms, treatment will continue for 35 cycles or until progressive disease, unacceptable toxicity, or pt/investigator decision. Response will be evaluated every 6 wk per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns; eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be assessed throughout treatment and for 30 d thereafter (90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 3 mo. OS and PFS per RECIST v1.1 are the primary study end points; secondary end points include ORR and duration of response. Enrollment in KEYNOTE-062 is ongoing and will continue until ~750 pts have enrolled. Clinical trial information: NCT02494583.

A phase III trial-in-progress comparing tislelizumab plus chemotherapy with placebo plus chemotherapy as first-line therapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2655-TPS2655
Author(s):  
Rui-hua Xu ◽  
Hendrik-Tobias Arkenau ◽  
Yung-Jue Bang ◽  
Crystal S. Denlinger ◽  
Ken Kato ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Tolerability Profile ◽  
First Line ◽  
Double Blind ◽  
First Line Therapy ◽  
Line Therapy

TPS2655 Background: In patients (pts) with locally advanced or metastatic G/GEJ cancer, fluoropyrimidine- and platinum (plt)-based combination chemotherapy is first-line standard of care. Despite improvement in chemotherapy regimens, outcomes are poor and survival remains low. Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding of FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports suggested tislelizumab, as a single agent and in combination with chemotherapy, was generally well tolerated and had antitumor activity in pts with advanced solid tumors, including G/GEJ cancer. Methods: This global, double-blind, randomized, phase 3 study (NCT03777657) is designed to compare plt/fluoropyrimidine + tislelizumab versus plt/fluoropyrimidine + placebo as first-line therapy for pts with locally advanced or metastatic G/GEJ cancer. Approximately 720 pts from 160 centers will be randomized 1:1 to receive tislelizumab (200 mg IV Q3W) or placebo (IV Q3W) in combination with chemotherapy. Oxaliplatin (130 mg/m² IV Q3W) plus capecitabine (1000 mg/m2 orally twice daily for 2 weeks) or cisplatin (80 mg/m² IV Q3W) plus 5-fluorouracil (800 mg/m2/day IV on Days 1–5 Q3W) will be used as backbone chemotherapy on an individual basis. Chemotherapy will be administered for up to 6 cycles; capecitabine maintenance therapy is optional for pts who received capecitabine and oxaliplatin. PD-L1 expression will be assessed using the VENTANA PD-L1 (SP263) assay. Progression-free survival and overall survival are primary endpoints in the intent-to-treat and PD-L1-positive analysis sets of the study. Secondary endpoints include overall response rate, duration of response, quality-of-life outcomes, and the safety/tolerability profile of combination therapy. Exploratory endpoints include disease control rate, time to response, and an analysis of potential predictive biomarkers including, but not limited to, PD-L1 expression. Clinical trial information: NCT03777657.

REGARD: A phase III, randomized, double-blinded trial of ramucirumab and best supportive care (BSC) versus placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing combination therapy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. LBA5-LBA5 ◽  
Author(s):  
Charles S. Fuchs ◽  
Jiri Tomasek ◽  
Jae Yong Cho ◽  
Filip Dumitru ◽  
Rodolfo Passalacqua ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Disease Progression ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Vegf Receptor ◽  
First Line ◽  
Double Blind ◽  
Cancer Pathogenesis ◽  
Line Therapy

LBA5 Background: VEGF and VEGF receptor-2 mediated signaling and angiogenesis may contribute to gastric cancer pathogenesis. Ramucirumab (RAM; IMC-1121B) is a fully human IgG1 monoclonal antibody targeting VEGF-receptor 2. We conducted a placebo-controlled, double-blind, phase III international trial to evaluate the safety and efficacy of RAM in pts with metastatic gastric or GEJ adenocarcinoma progressing on first-line platinum- and/or fluoropyrimidine containing combination therapy. Methods: Pts were randomized 2:1 to receive RAM (8 mg/kg IV) plus BSC or placebo (PL) plus BSC every 2 weeks (wks) until disease progression, unacceptable toxicity, or death. Eligible patients had disease progression within 4 months (m) after 1st-line therapy for metastatic disease or within 6 m after adjuvant therapy. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), 12-wk PFS rate, overall response rate (ORR) and safety. Results: From 10/09 to 01/12, 355 pts were randomized (RAM: 238; PL: 117). Baseline characteristics were well balanced between arms. The Hazard Ratio (HR) for OS was 0.776 (95% CI, 0.603-0.998; p = 0.0473). Median OS was 5.2 m for RAM and 3.8 m for PL. The HR for PFS was 0.483 (95% CI, 0.376-0.620; p < 0.0001). Median PFS was 2.1 m for RAM and 1.3 m for PL. 12-wk PFS was 40% for RAM and 16% for PL. ORR was 3.4% for RAM and 2.6% for PL. Disease control rate was 49% for RAM and 23% for PL (p < 0.0001). Use of anti-cancer therapy post-study: 32% RAM; 39% PL. The most frequent of grade ≥ 3 adverse events (AEs) were: hypertension (7.2% RAM; 2.6% PL), anemia (6.4% RAM; 7.8% PL), abdominal pain (5.1% RAM; 2.6% PL), ascites (4.2% RAM; 4.3% PL), fatigue (4.2% RAM; 3.5% PL), decreased appetite (3.4% RAM; 3.5% PL) and hyponatremia (3.4% RAM; 0.9% PL). Conclusions: Ramucirumab conferred a statistically significant benefit in OS and PFS compared to PL in metastatic gastric or GEJ adenocarcinoma following progression on 1st-line therapy with an acceptable safety profile. Clinical trial information: NCT00917384.

Assessment of ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients (pts) with advanced HER2-negative gastric or gastroesophageal junction cancers: The ARMANI phase III trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4151-TPS4151 ◽  
Author(s):  
Federica Morano ◽  
Monica Niger ◽  
Salvatore Corallo ◽  
Sara Lonardi ◽  
Stefano Tamberi ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2

TPS4151 Background: Platinum/fluoropyrimidine regimens are the backbone of first-line therapy for advanced gastric cancer (AGC). The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only 40% of AGC pts are eligible for second-line treatment. This study aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after a first-line with a platinum/fluoropyrimidine regimen. The hypothesis is that the early administration of an active, non-cross resistant regimen may delay disease progression and, consequently, improve pts’ quality of life. This strategy may also rescue all those subjects that become ineligible for a second-line therapy due to the rapid clinical deterioration. Methods: This is a randomized, open-label, multicenter, phase III trial. Eligibility criteria are: unresectable/metastatic HER-2 negative AGC or gastroesophageal junction (GEJ) cancer; ECOG PS 0-1; measurable and/or evaluable disease by RECIST v1.1; no progression after 3 months of therapy with either FOLFOX4, mFOLFOX6 or XELOX . The primary endpoint is to compare PFS of pts in ARM A (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine) versus ARM B (switch maintenance to ramucirumab and placlitaxel). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of pts receiving a second-line therapy per treatment arm, safety and quality of life. Exploratory analyses to identify primary resistance and prognosis biomarkers are planned, including Next-Generation Sequencing (NGS) on archival tumor tissues. The ARMANI study is sponsored by the Fondazione IRCCS Istituto Nazionale dei Tumori and it is ongoing at 29 Italian centers with a planned population of 280 pts. Clinical trial information: NCT02934464.

Sign in / Sign up

Export Citation Format

Share Document