Pooled safety results from SPIRITT: A multicenter, open-label, randomized, phase II study of FOLFIRI with panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 477-477 ◽  
Author(s):  
J. R. Hecht ◽  
S. R. Dakhil ◽  
M. N. Saleh ◽  
B. Piperdi ◽  
M. Cline-Burkhardt ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Patient Reported

477 Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR) approved as monotherapy in pts with chemorefractory mCRC. Many pts with mCRC who have progressed on a bev-containing regimen receive second-line bev + chemotherapy despite the lack of prospective, randomized data supporting this approach. A phase III study recently showed that pmab + second-line FOLFIRI improved progression-free survival (PFS) in pts with wild-type (WT) KRAS tumors vs chemotherapy alone. This study was amended after enrollment began to focus hypothesis testing on the WT KRAS population and is evaluating the safety and efficacy of pmab + FOLFIRI vs bev + FOLFIRI in pts who received first-line therapy with an oxaliplatin-based regimen + bev. Methods: This is a randomized, phase II, open-label study in pts with mCRC with disease progression or intolerability after ≥ 4 doses of first-line oxaliplatin-based chemotherapy + bev. Pts are randomized 1:1 to receive either 6 mg/kg pmab Q2W + FOLFIRI or bev (given at institutional standard dose Q2W) + FOLFIRI. Tx is administered until disease progression (PD), death, or withdrawal from study. The primary endpoint is PFS in patients with WT KRAS tumors. Other endpoints include objective response rate, overall survival, safety, and patient-reported outcomes. Results: At the time of data cutoff, 216 of 277 planned pts were enrolled. 175 (81%) pts discontinued study tx and 39 (18%) pts remain on tx. Any grade adverse events (AEs) were reported in 197 (92%) pts. 38 (18%) pts had AEs that led to withdrawal from tx or study. Serious AEs were reported in 66 (31%) pts and included gastrointestinal disorders (13%), infections and infestations (8%), respiratory disorders (7%), and metabolism and nutrition disorders (7%). Fatal AEs were reported in 18 (8%) pts of which 9 (4%) were related to disease progression. Conclusions: The aggregate safety profile is consistent with expected toxicities of FOLFIRI in combination with an anti-EGFR or an anti-VEGF targeted therapy in second-line mCRC. Detailed pooled safety results will be presented at the meeting. [Table: see text]

A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4139-4139
Author(s):  
Chris Poki Leung ◽  
Minal A. Barve ◽  
Ming-Shiang Wu ◽  
Kathleen F. Pirollo ◽  
James F. Strauss ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Tp53 Gene ◽  
Phase Iii ◽  
Published Data ◽  
Line Treatment ◽  
Second Line ◽  
First Line

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
David Malka ◽  
Laetitia Fartoux ◽  
Vanessa Rousseau ◽  
Tanja Trarbach ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Mutational Analysis ◽  
Metabolic Response ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

Multicenter phase II clinical trial of everolimus in Japanese patients with unresectable or metastatic renal cell carcinoma (mRCC) after failure of treatment with first-line tyrosine kinase inhibitor (TKI) therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 455-455
Author(s):  
Seiichiro Ozono ◽  
Masafumi Oyama ◽  
Masahiro Nozawa ◽  
Kiyohide Fujimoto ◽  
Ken Kishida ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Line Setting

455 Background: Everolimus has shown the efficacy and the safety in the phase III trial (RECORD-1) in patients with mRCC after failure of Vascular Endothelial Growth Factor Receptor-TKI. However, 26% of patients received two TKIs (sunitinib and sorafenib) as previous therapy in RECORD-1. In addition, as pre-treatment before TKI, 65% of patients received cytokine therapy and 13% of patients received chemotherapy. Therefore, there is still no clear evidence of everolimus as second line setting after failure of 1st-line TKI therapy. Methods: This study is an open-label, multi-center, single-arm, phase II trial. Primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival, objective response rate, time-to-treatment-failure, safety and quality of life (EORTC QLQ-C30, FKSI-DRS, EQ-5D). Key eligibility criteria are RCC with clear cell component, patients who received one TKI as first line therapy, patients who did not receive cytokine and chemotherapy and ECOG performance status 0-1. Results: 57 patients were enrolled from 02/11 to 12/12. Median age was 63 years, common sites of metastasis were lung (32.7%) and bone (12.2%), 79.6% had previous nephrectomy, previous TKI therapy were sunitinib (69.4%), sorafenib (22.4%) and axitinib (8.2%). Median PFS was 4.4 months (95% confidence interval: 3.7-6.0). 8.2% had partial response and 57.1% had stable disease according to RECIST v.1.0. The incidence of adverse events (AEs) of all grades was 95.9%. Major AEs were stomatitis (49.0%), hypertriglyceridemia (26.5%) and hypercholesterolemia (24.5%). Serious AEs were stomatitis (10.2%), interstitial lung disease (6.1%) and rash (6.1%). There were no treatment related deaths. All QOL scores were not changed at 2 months, while dyspnea and global health scores of EORTC QLQ-C30 and FKSI-DRS score were worsened at 4 months. Conclusions: This study is a first report of everolimus as second line setting after failure of 1st-line TKI. Further study and long-term follow-up would be warranted. Clinical trial information: UMIN000004742.

Phase III randomized sequential open-label study to evaluate the efficacy of FOLFOX + panitumumab followed by FOLFIRI + bevacizumab (Sequence 1) versus FOLFOX+ bevacizumab followed by FOLFIRI + panitumumab (Sequence 2) in untreated patients with wild-type RAS metastatic, primary left (L)-sided, unresectable colorectal cancer (CRC): The CR-SEQUENCE.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS3618-TPS3618
Author(s):  
Ramon Salazar ◽  
Alfredo Carrato ◽  
Teresa Garcia Garcia ◽  
Javier Gallego Plazas ◽  
Auxiliadora Gómez-España ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Objective Response ◽  
Primary Objective ◽  
Phase Iii ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Open Label ◽  
Anti Vegf

TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they are added in first and second-line in L-sided CRC. The conflicting results in anti-VEGF vs. anti-EGFR studies (FIRE-3, PEAK and CALGB/SWOG 80405 studies) suggest that the sequence of targeted therapies added to FOLFOX or FOLFIRI regimens in first- and second-line treatment could be an important factor in the overall survival (OS) of mCRC patients. Currently, there are no randomized data on the sequential use of an anti-EGFR followed by an anti-VEGF or vice versa. Therefore, the aim of this randomized clinical trial is to compare the efficacy of two treatment sequences, panitumumab followed by bevacizumab versus bevacizumab followed by panitumumab in combination with FOLFOX chemotherapy in first-line and with FOLFIRI in second-line in patients with wild-type RAS, primary L-sided, metastatic colorectal cancer (mCRC). Methods: A phase III, multicentre, open-label and randomized two-arm clinical trial. Untreated patients with wild-type RAS mCRC (determined locally), primary L-sided and unresectable will be screened for this trial. Eligible patients will be randomized 1:1 to receive first-line (1L) panitumumab plus FOLFOX and then bevacizumab plus FOLFIRI as second-line (2L) treatment (Seq. 1) or bevacizumab plus FOLFOX as 1L and then panitumumab plus FOLFIRI as 2L treatment (Seq. 2). Randomization will be stratified by number of metastatic organs involved (1 vs > 1). Primary objective is the comparison of the progression free survival (PFS) rate at 35 months (m) of Seq 1 vs Seq. 2. Secondary objectives: PFS from randomization to 2nd progression or death, OS rate at 35 months and OS of Seq. 1 vs Seq. 2; PFS, objective response rate, disease control rate, early tumour shrinkage, Depth of Response, duration and time to response and safety in 1L treatment and in 2L treatment in each Sequence arm. Exploratory objectives: impact of baseline biomarkers predictive of the efficacy in each Sequence arm and the clinical impact of clonal dynamics by longitudinal analysis of circulating tumour deoxyribonucleic acid (ctDNA) in plasma. The trial is in progress; 28 of up to 370 planned patients have been recruited at the end of January 2019 (first patient in 31 October 2018). Clinical trial information: NCT03635021.

Quattro-II study: A multicenter randomized phase II study comparing capoxiri plus bevacizumab with FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer as the first-line treatment.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS267-TPS267
Author(s):  
Akihito Tsuji ◽  
Takayuki Yoshino ◽  
Takeharu Yamanaka ◽  
Hideaki Bando ◽  
Hironaga Satake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Recommended Dose ◽  
Hematologic Toxicity ◽  
First Line ◽  
Randomized Phase Ii ◽  
Patient Reported

TPS267 Background: The first-line FOLFOXIRI with Bevacizumab (BEV) is highly effective and regarded as one of standard-of-care treatments in patients (pts) with metastatic colorectal cancer (mCRC) despite a high incidence of adverse events (AEs) such as neutropenia and diarrhea. The AXEPT, Asian Phase III study showed CAPIRI+BEV [Capecitabine (CAP: 1600 mg/m2), Irinotecan (IRI: 200 mg/m2) and BEV (7.5 mg/m2)] q3wk was non-inferior to FOLFIRI+BEV in pts with the second-line mCRC, with a lower incidence hematologic toxicity favoring CAPIRI+BEV over FOLFIRI+BEV. Based on these, a reduced dose of CAP and IRI regimen in combination with Oxaliplatin (OX) and BEV, CAPOXIRI+BEV may be more feasible than FOLFOXIRI+BEV, without compromising efficacy. Methods: QUATTRO-II is an open-label, multicenter, randomized phase II study. Key eligibility criteria are as follows; age ≥20 years, ECOG performance status (PS) 0-1 (≥71 years age: PS 0), adequate organ function, and UGT1A1 single-heterozygous (UGT1A1*1/*6 or *1/*28) or wild-type (*1/*1) genotype. Pts are randomized to either the recommended dose of CAPOXIRI+BEV or FOLFOXIRI+BEV (OX: 85 mg/m2, IRI: 165 mg/m2, l-leucovorin: 200 mg/m2, 5-FU: 3200 mg/m2), with the strata of RAS/ BRAF status, previous adjuvant OX, tumor sidedness, and UGT1A1 status. Induction triplet chemotherapy plus BEV treatments are administered for up to 4 months followed by fluoropyrimidine plus BEV maintenance. The recommended dose of CAPOXIRI+BEV will be determined as a safety-lead-in before moving forward to the phase II main part. The primary endpoint is progression-free survival (PFS). The similarity of PFS between the two arms is evaluated by observing whether the point estimate of hazard ratio (HR) for PFS falls in between 0.80 and 1.25. Ensuring 70% probability that the observed HR will be “0.8<HR<1.25” under the assumption of the true HR of 1.0, a total of 100 patients will be needed with 3-year study period. Secondary endpoints included overall survival, overall response rate, safety, and patient-reported outcome (FACT/GOG-Ntx4). The enrollment started in October 2019. Clinical trial information: NCT04097444.

Surufatinib in combination with toripalimab in patients with advanced neuroendocrine carcinoma: Results from a multicenter, open-label, single-arm, phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16199-e16199
Author(s):  
Lin Shen ◽  
Xianjun Yu ◽  
Ming Lu ◽  
Xing Zhang ◽  
Ying Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Neuroendocrine Carcinoma ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Open Label ◽  
Grade 3

e16199 Background: Patients with advanced neuroendocrine carcinoma (NEC) have a poor prognosis and limited treatment option after first-line treatment. Surufatinib, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1 and CSF-1R, has been approved in patients with advanced or metastatic extra-pancreatic neuroendocrine tumors in China. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Surufatinib modulates tumor immune microenvironment and has shown promising antitumor activity in combination with toripalimab in solid tumors, including neuroendocrine tumor and neuroendocrine carcinoma. Herein, we reported the efficacy and safety of surufatinib in combination with toripalimab in a cohort of advanced NEC patients. Methods: The multicenter, open-label, single-arm phase II clinical trial enrolled advanced NEC patients refractory to first-line chemotherapy, and received surufatinib 250 mg once a day orally plus toripalimab 240 mg intravenously on day 1 of a 21-day cycle. The primary end point is objective response rate (ORR) per RECIST 1.1. Results: Twenty-one patients enrolled and received combination therapy. At data cut-off (December 31, 2020), the average treatment cycles were 5.1±3.69 for surufatinib and 5.0±3.68 for toripalimab. Among 20 tumor evaluable patients, 4 patients achieved confirmed PR and 10 patients achieved stable disease. The ORR and disease control rate (DCR) are 20 % (95%CI: 5.7%-43.7%) and 70% (95%CI: 45.7%-88.1%) respectively. The median PFS is 3.94 months (95%CI: 1.31- unknown). OS is not mature till data cut-off. Adverse events (AEs) reported as related to treatment (TRAE) occurred in 100% of patients, of which Grade≥3 TRAEs occurred in 33.3% of patients. The reported Grade≥3 TRAEs were hypertension in 2 (9.5%) patients, and upper abdominal pain, oral mucositis, neutrophil count decreased, leukocyte count decreased, dermatitis, anemia and backache in 1 (4.8%) patient each. Immune related Grade ≥3 AEs, Gamma-glutamyl transpeptidase increased and dermatitis, occurred in 2 (9.5%) patients, respectively. TRAE caused surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious AEs nor AEs inducing treatment discontinuations or deaths. Conclusions: As there is no standard second-line treatment, this combination of surufatinib and toripalimab might offer a new promising choice to treat NEC as second-line treatment due to good efficacy and manageable treatment related toxicities. Clinical trial information: NCT04169672.

A randomized, multicenter, double-blind, placebo (PBO)-controlled phase III study of paclitaxel (PTX) with or without ramucirumab (IMC-1121B; RAM) in patients (pts) with metastatic gastric adenocarcinoma, refractory to or progressive after first-line therapy with platinum (PLT) and fluoropyrimidine (FP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4139-TPS4139 ◽  
Author(s):  
Hansjochen Wilke ◽  
David Cunningham ◽  
Atsushi Ohtsu ◽  
Ulrike Nuber ◽  
Rolf Bruns ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Phase Iii ◽  
Vegf Receptor ◽  
First Line ◽  
Vegf Expression ◽  
First Line Therapy ◽  
Line Therapy ◽  
Patient Reported

TPS4139 Background: Vascular endothelial growth factor (VEGF) expression in gastric cancer (GC) is associated with more aggressive clinical disease. VEGF expression in resected GC is associated with tumor recurrence and shorter survival. Data from Phase 2 and 3 studies suggest that agents targeting the VEGF pathway improve the efficacy of some chemotherapy regimens in 1st- and 2nd-line treatment of patients with gastric or gastroesophageal carcinomas. RAM, a fully human monoclonal antibody, binds to the VEGF receptor-2 (VEGFR-2), potently blocks the binding of VEGF to VEGFR-2, inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGF-induced mitogenesis of human endothelial cells. Methods: Pts are randomized 1:1 to receive PTX + RAM or PTX + PBO until disease progression or intolerable toxicity (28-day cycle; RAM/PBO 8 mg/kg Days 1, 15; PTX 80 mg/m2 Days 1, 8, 15). Eligibility includes metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma; prior first-line therapy with any PLT/FP doublet with or without anthracycline; progressive disease during or following first-line therapy; ECOG PS 0-1; bilirubin ≤ 1.5 × upper limit of normal (ULN), transaminases ≤ 3 × ULN for ALAT/ASAT if no liver metastases, < 5 × ULN if liver metastases; creatinine ≤ 1.5 × ULN; absolute neutrophil count ≥ 1.5 × 109/L, hemoglobin ≥ 9 g/dL; platelets ≥ 100 × 109/L. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival, time to progression, best overall response, objective response rate, safety, patient-reported outcome measures, pharmacodynamics, immunogenicity, and pharmacokinetics. This study, powered at 90% to show an increase in OS (mdn: 7 m PTX + PBO, 9.33 m PTX + RAM) at a 1-sided 2.5% significance level, will randomize 663 pts. As of 18 January 2012, approximately 58% of planned pts were randomized. The IDMC reviewed this study 23 June and 01 December 2011 and recommended the study continue unmodified.

LUX-Lung 6: A randomized, open-label, phase III study of afatinib (A) versus gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lung.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8016-8016 ◽  
Author(s):  
Yi Long Wu ◽  
Caicun Zhou ◽  
Cheng-Ping Hu ◽  
Ji Feng Feng ◽  
Shun Lu ◽  
...  
Keyword(s):  
Objective Response ◽  
Prospective Trial ◽  
Phase Iii ◽  
Egfr Mutations ◽  
First Line ◽  
Open Label ◽  
Asian Patients ◽  
Patient Reported ◽  
Exon 19 Deletion ◽  
Independent Review

8016 Background: A is an oral, irreversible, ErbB Family Blocker, blocking signaling from EGFR (ErbB1), HER2 (ErbB2) and ErbB4. A was superior to first-line pemetrexed/cisplatin in a global phase III trial (LUX-Lung 3) in EGFR M+ NSCLC. This study compared the safety and efficacy of first-line A with GC in EGFR M+ Asian pts. Methods: The trial was conducted in Asian countries. Following central testing for EGFR mutations (TheraScreen EGFR RGQ PCR kit), 364 pts (stage IIIB/IV, PS 0–1, chemo-naïve) were randomized 2:1 (A: 242; GC: 122) to daily A 40 mg or IV GC (1,000 mg/m2 D1, 8 + 75 mg/m2q21 days up to 6 cycles). Primary endpoint was PFS by central independent review. Results: Baseline characteristics were balanced in both arms: Female (64.0 vs 68.0%), non-smoker (74.8 vs 81.1%), exon 19 deletion (51.2 vs 50.8%), L858R (38.0 vs 37.7%) in A and GC arms, respectively. PFS was significantly prolonged with A compared with GC by independent review (median PFS 11.0 vs 5.6 months, HR=0.28, p<0.0001); this finding was consistent across all subgroups. Results from the investigator review were similar: HR=0.26, p<0.0001, median 13.7 (A) vs 5.6 months (GC). Objective response (66.9% vs 23.0%, p<0.0001) and disease control (92.6% vs 76.2%, p<0.0001) rates (ORR/DCR) were significantly higher with A. OS, based on 43% of events shows HR=0.95, p=0.7593. Drug-related AEs of ≥G3 were reported in 36.0% (A) and 60.2% (GC) of pts, the most common of which were rash/acne (14.6%), diarrhea (5.4%) and stomatitis/mucositis (5.4%) with A and neutropenia (17.7%), vomiting (15.9%) and leukopenia (13.3%) with GC. Related AEs led to discontinuation in 5.9% (A) and 39.8% (GC) of pts. Patient reported-outcomes (PROs) showed significantly better control of cancer-related dyspnea, cough and pain with A. Conclusions: In EGFR M+ Asian pts, A significantly prolonged PFS with significant improvements in ORR, DCR, PROs. AEs in both arms were as expected, with a more favorable safety profile with A. LUX-Lung 6 is the largest prospective trial in EGFR M+ lung cancer, providing further evidence of superiority of A over standard chemotherapy in this setting. Clinical trial information: NCT01121393.

The Canadian Cancer Trials Group PA.7 trial: Results from the safety run in of a randomized phase II study of gemcitabine (GEM) and nab-paclitaxel (Nab-P) versus GEM, nab-P, durvalumab (D), and tremelimumab (T) as first-line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 349-349 ◽  
Author(s):  
Daniel John Renouf ◽  
Neesha C. Dhani ◽  
Petr Kavan ◽  
Derek J. Jonker ◽  
Alice Chia-chi Wei ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Human Monoclonal Antibody ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

349 Background: GEM and Nab-P is a standard first line therapy for mPDAC based on the MPACT Trial. D is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. T is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). PA.7 is designed to evaluate whether combining PD-L1 and CTLA-4 inhibition with GEM and Nab-P increases treatment efficacy. Methods: This randomized phase II study (ClinicalTrials.gov NCT02879318) is assessing the efficacy and safety of GEM and Nab-P vs. GEM, Nab-P, D, and T in patients (pts) with mPDAC (n = 190). Pts with untreated mPDAC and good performance status (ECOG PS 0-1) are eligible. A safety run in was planned for 10 pts receiving GEM, Nab-P, D and T. The study is then planned to randomize pts in a 2:1 ratio to receive GEM (1000mg/m2 D1, 8, 15); Nab-P (125mg/m2 D1, 8, 15); D (1500 mg) D1 q 28 days and T (75 mg) D1 for first 4 cycles vs. GEM and Nab-P alone. The primary endpoint is overall survival (OS); secondary endpoints include progression free survival (PFS), safety, overall response rate and quality of life. Results: 11 pts were enrolled in the safety run in (2 final pts enrolled on the same day). Median (Med) age = 59; 9 male/ 2 female; 2 ECOG 0/ 9 ECOG 1; no pts had prior adjuvant therapy. Med follow-up was 8.3 months at the time of data lock. Med number of treatment cycles was 6 (3-10). The most common Grade 3 or greater adverse events included fatigue (27%), anemia (36%), abnormal WBC (27%), hyponatremia (27%), hypoalbuminemia (45%), and abnormal lipase (45%). 1 pt (9.1%) experienced grade 3 colitis. 8/11 pts (73%) had a partial response, with the med duration of 7.4 months. Disease control rate was 100%. Med PFS was 7.9 months (95% C.I. 3.5-9.2 months). 6-month survival rate was 80% (95% C.I 40.9%-94.6%). Med OS has not been reached. Conclusions: The combination of GEM, Nab-P, D and T was well tolerated and promising efficacy signals were noted. The originally designed randomized phase II study is ongoing, and an international randomized phase III trial is planned. Clinical trial information: NCT02879318.

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