Envafolimab plus chemotherapy in advanced gastric or gastroesophageal junction (G/GEJ) cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16585-e16585
Author(s):  
Xianli Yin ◽  
Yun Zhang ◽  
Yanhong Deng ◽  
Nong Xu ◽  
Jianming Xu ◽  
...  
Keyword(s):  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Single Domain Antibody ◽  
Ecog Performance Status ◽  
First Line Therapy ◽  
Platelet Disorder ◽  
Duration Of Response

e16585 Background: Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc, formulated for subcutaneously (SC) injection. This study examined the feasibility of combining envafolimab with chemotherapy in advanced G/GEJ cancer. Methods: This study was a single arm, phase Ⅱ trial in adult subjects with previously untreated advanced G/GEJ cancer. Subjects received 8 cycles (2 weeks each) of envafolimab plus FOLFOX regimen followed by envafolimab and 5-FU until progression or unacceptable toxicity. Envafolimab was administrated SC at 5 mg/kg on day 1 of each cycle; FOLFOX consisted of 80 mg/m2 oxaliplatin, 400 mg/m2 5-FU and 400 mg/m2 leucovorin intravenous infusion on day 1, 2400 mg/m2 5-FU administered with a 48-hour continuous infusion on day 1 and 2. Tumor was assessed every 6 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Primary endpoints were safety and tolerability. Toxicity was graded using CTCAE v5.0. Secondary endpoints included objective response rate (ORR), duration of response (DoR). and progression free survival (PFS). Results: A total of 15 subjects were treated and evaluable for response. ECOG performance status was 1 in 80% of subjects. Majority had gastric cancer (86.7%). At the data cutoff, the minimum follow-up was 6 months. The treatment emergent adverse event (TEAE) occurrence was 100% (all grades) and 73.3% (grades 3-4). The most frequent grade 3-4 TEAE included neutrophil count decreased 46.7%, anemia 20.0%, and platelet disorder 20% (3/15). Confirmed ORR was 60% (unconfirmed ORR: 73.3%). Median DOR was not reached. Median PFS was 6.8 months. Conclusions: Envafolimab plus FOLFOX demonstrated a manageable safety profile with promising clinical efficacy as a first line therapy for advanced G/GEJ cancer. Clinical trial information: CTR20181124 .

Phase II efficacy and safety study of nintedanib versus sunitinib in previously untreated renal cell carcinoma (RCC) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4506-4506 ◽  
Author(s):  
Tim Eisen ◽  
Yaroslav Shparyk ◽  
Robert Jones ◽  
Nicholas James MacLeod ◽  
Graham Temple ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Qtc Interval ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Interval Change ◽  
First Line Therapy

4506 Background: Sunitinib (S) is established as a standard first-line therapy for patients (pts) with advanced RCC. However, treatment can be limited by the occurrence of drug-related adverse events (AEs). This Phase II study assessed the efficacy and safety of nintedanib (N) – a potent, triple angiokinase inhibitor of VEGFR-1–3, PDGFR-α/β, and FGFR-1–3, as well as RET and Flt3 – vs S in previously untreated pts with RCC. Methods: Ninety-nine eligible pts (96 of whom were treated) with advanced, unresectable/recurrent clear cell RCC, an ECOG performance status of 0–1, and no prior systemic therapy were randomized 2:1 to receive N 200 mg twice daily (n=64; given in 4-week cycles) or S 50 mg once daily (n=32; 4 weeks on, 2 weeks off schedule). Treatment continued until disease progression or unacceptable drug-related AEs. Primary endpoints were progression-free survival at 9 months (PFS-9) and, in N-treated pts only, QTc interval change (baseline to day 15). Secondary endpoints included PFS, objective response rate (ORR; RECIST 1.1), overall survival (OS), time to progression (TTP), time to treatment failure (TTF), and AEs. Results: Baseline characteristics were balanced between the arms. PFS-9 was not statistically significantly different between N- and S-treated pts (43 vs 45%; p=0.85). There were also no statistically significant differences between N and S with regard to PFS (median: 8.44 vs 8.38 mo; hazard ratio: 1.16; 95% CI: 0.71–1.89; p=0.56), confirmed ORR (18.8 vs 31.3%; p=0.19), OS (median: 20.37 vs 21.22 mo; p=0.63), TTP (median: 8.48 vs 8.54 mo; p=0.52), and TTF (median: 8.41 vs 8.36 mo; p=0.46). Grade ≥3 AEs occurred in 47% of N-treated pts and 56% of S-treated pts. Common AEs (all grades; N vs S) included diarrhea (61 vs 50%), nausea (38 vs 34%), fatigue (both 25%), and vomiting (16 vs 22%). Dermatologic AEs (8 vs 47%) were less frequent with N than S. There was no increase from baseline in QTc >60 ms on days 1 or 15 in N-treated pts, and there was no relationship between N exposure and QT interval change. Conclusions: N demonstrated similar efficacy to S and had a manageable safety profile, including a lower incidence of dermatologic AEs vs S. In addition, N was not associated with QT prolongation. Clinical trial information: NCT01024920.

Pembrolizumab (pembro) versus standard of care chemotherapy (chemo) in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4523-4523 ◽  
Author(s):  
Hironaga Satake ◽  
Keun Wook Lee ◽  
Hyun Cheol Chung ◽  
Jeeyun Lee ◽  
Kensei Yamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Asian Population ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
End Points ◽  
Asian Patients

4523 Background: First-line treatment with pembro or pembro + chemo vs chemo alone was evaluated in patients with PD-L1 combined positive score (CPS) ≥1, HER2-negative advanced gastric cancer in the randomized, active-controlled, phase 3 KEYNOTE-062 study (NCT02494583). We present results from the Asian subpopulation receiving pembro monotherapy or chemo. Methods: Eligible patients were randomly assigned 1:1:1 to pembro 200 mg, pembro + chemo (cisplatin + 5-FU or capecitabine), or placebo + chemo every 3 weeks for ≤35 cycles (~2 years). Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary end points for this analysis were overall survival (OS) in patients with CPS ≥1 and patients with CPS ≥10; progression-free survival (PFS) and objective response rate (ORR) were exploratory end points. Data cutoff was March 26, 2019. Results: Globally, 256 patients received pembro monotherapy and 250 received chemo. Pembro was noninferior to chemo for OS in CPS ≥1 per prespecified margins (median OS, 10.6 vs 11.1 months, respectively; HR [99.2% CI], 0.91 [0.69-1.18]). In the Asian population 62 patients received pembro and 61 received chemo; 26 and 22 had CPS ≥10 (Table). Compared with the global population, Asian patients had a higher proportion of ECOG performance status 0, more diagnoses of stomach cancer, and a greater proportion with 0-2 metastatic sites. Median OS was longer with pembro than chemo using both CPS cutoffs (HR [95% CI]: CPS ≥1, 0.54 [0.35-0.82]; CPS ≥10, 0.43 [0.21-0.89]); 12- and 24-month OS rates were higher for pembro using both CPS cutoffs (12-month OS: CPS ≥1, 69% vs 54%; CPS ≥10, 81% vs 68%; 24-month OS: CPS ≥1, 45% vs 23%; CPS ≥10, 54% vs 27%). The HR (95% CI) for PFS was 1.11 (0.76-1.64) for CPS ≥1 and 0.71 (0.36-1.39) for CPS ≥10. Conclusions: In Asian patients with advanced gastric cancer, OS favored pembro in patients with CPS ≥1 and CPS ≥10. Clinical trial information: NCT02494583 . [Table: see text]

A randomized phase II study of axitinib in combination with pemetrexed/cisplatin (pem/cis) as first-line therapy for nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7551-7551 ◽  
Author(s):  
Chandra Prakash Belani ◽  
Nobuyuki Yamamoto ◽  
Igor Bondarenko ◽  
Sergey V Orlov ◽  
Jie Tang ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Starting Dose ◽  
Grade 3 ◽  
To Receive

7551 Background: Axitinib is a potent and selective second-generation inhibitor of VEGF receptors 1, 2, and 3 that has promising single-agent activity in advanced NSCLC. Efficacy and safety of axitinib (in 2 dosing schedules) combined with pem/ciswere evaluatedfor non-squamous NSCLC. Methods: Patients with confirmed stage IIIB, IV, or recurrent non-squamous NSCLC and ECOG performance status (PS) 0 or 1 were stratified by gender and PS, and randomized 1:1:1 to receive six 21-day cycles of axitinib continuously plus pem/cis (arm I); axitinib on Days 2 through 19 followed by a 3-day interruption plus pem/cis (arm II); or pem/cis alone (arm III). Axitinib was administered at a starting dose of 5 mg BID. Pem/cis (500/75 mg/m2) was infused on Day 1 of each cycle. Primary endpoint was progression-free survival (PFS). Results: Baseline characteristics of patients in arm I (n=55), arm II (n=58), or arm III (n=57) ranged between 59–62 yr median age; 62–65% male; 71–85% White; 73–85% current/ex-smokers; and 43–47% PS 0. There were no significant differences in PFS or overall survival (OS) between axitinib-containing arms I and II compared with pem/cis alone, but objective response rates (ORR) were higher (Table). Most common all causality grade 3 adverse events (AEs) in arm I, II, and III, respectively, were hypertension (20%, 17%, 0%); neutropenia (18%, 10%, 9%); nausea (16%, 5%, 7%); vomiting (13%, 5%, 4%); fatigue (11%,16%,16%); and anemia (7%, 14%, 9%). Grade 4 AEs observed in >1 patient were asthenia and pulmonary embolism (2 patients each in arm II). Conclusions: Axitinib combined with pem/cis was generally well tolerated, but efficacy was not significantly better than pem/cis alone in non-squamous NSCLC. [Table: see text]

The association of tissue tumor mutational burden (tTMB) using the Foundation Medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (pts) with gastric cancer (GC) from KEYNOTE-061.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4537-4537 ◽  
Author(s):  
Kohei Shitara ◽  
Mustafa Özgüroğlu ◽  
Yung-Jue Bang ◽  
Maria Di Bartolomeo ◽  
Mario Mandalà ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Positive Association ◽  
Progression Free Survival ◽  
Wald Test ◽  
Cox Proportional Hazards ◽  
Open Label ◽  
Ecog Performance Status

4537 Background: KEYNOTE-061 (NCT02370498) was a randomized, open-label, phase 3 study of pembrolizumab vs paclitaxel in pts with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with tumor progression after first-line therapy (N = 592). In this analysis, we evaluated tTMB using FoundationOne CDx (F1CDx; Foundation Medicine) in pts with gastric or GEJ cancer in KEYNOTE-061. Methods: In pts with evaluable F1CDx tTMB data (n = 204), we analyzed the association of tTMB with confirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) within each treatment arm using one-sided (pembrolizumab) and two-sided (paclitaxel) Wald test nominal P for logistic regression (ORR) and Cox proportional hazards regression (PFS; OS) adjusted for ECOG performance status; significance was prespecified at 0.05. The clinical utility of tTMB was assessed using the prespecified cutoff of 10 mut/Mb for F1CDx. Clinical data cutoff: Oct 26, 2017. Results: tTMB was positively associated with ORR ( P < 0.001; AUROC, 0.68), PFS ( P < 0.001), and OS ( P = 0.003) with pembrolizumab but not paclitaxel (ORR, P = 0.047; AUROC, 0.30; PFS, P = 0.605; OS, P = 0.084). Pt outcomes by tTMB cutoff are reported in the Table; prevalence of TMB ≥10 mut/Mb was 17%. In pts with microsatellite stable disease-only, HRs (95% CI) by treatment arm for OS by F1CDx cutoff were 0.40 (0.14-1.17) for tTMB ≥10 mut/Mb (n = 21) vs 0.97 (0.70-1.34) for tTMB <10 mut/Mb (n = 168). Conclusions: In this exploratory analysis from KEYNOTE-061, tTMB as determined by F1CDx demonstrated a positive association with clinical outcomes with pembrolizumab, but not paclitaxel, in pts with GC; these findings are consistent with those reported with whole exome sequencing. Pembrolizumab demonstrated an OS benefit vs paclitaxel in the subgroup with tTMB ≥10 mut/Mb, which remained when pts with microsatellite instability-high disease were excluded. Clinical trial information: NCT02370498 . [Table: see text]

Impact of primary tumour location (PTL) on outcomes in patients (pts) with metastatic colorectal cancer (mCRC) undergoing first-line panitumumab (Pmab) + FOLFIRI treatment .

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 820-820 ◽  
Author(s):  
Meinolf Karthaus ◽  
Marc Van Den Eynde ◽  
Laurent Mineur ◽  
Josef Thaler ◽  
Reija Koukakis ◽  
...  
Keyword(s):  
Primary Tumour ◽  
Performance Status ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
First Line ◽  
Ecog Performance Status ◽  
Depth Of Response ◽  
Study Results ◽  
Duration Of Response

820 Background: Prognosis in pts with mCRC is affected by PTL; PTL may also affect the activity of the epidermal growth factor receptor inhibitor Pmab (+ FOLFIRI). Methods: In this phase II, single-arm study (NCT00508404), pts received first-line Pmab+FOLFIRI Q2W until disease progression (PD); primary endpoint: objective response rate (ORR). Analyses included pts with RAS wild-type (WT) mCRC (no mutations in KRAS/ NRAS exons 2, 3 and 4). Baseline demographics/disease characteristics were summarised by PTL and the effect of PTL on outcome was analysed. Early tumour shrinkage (ETS) was defined as a ≥30% reduction in the sum of the longest diameters of measurable target lesions at week 8. Depth of response (DpR) was the maximum % change from baseline to nadir in pts with shrinkage, or the change at PD in pts with no shrinkage. DpR was positive for shrinkage, negative for growth and zero for no change. Progression-free survival (PFS) was analysed by PTL and ETS status. There was no long-term follow-up of overall survival in this study. Results: PTL could be determined in 52/69 (75%) RAS WT pts; 45/52 (87%) had left (L)-sided disease. Pts with L- vs right (R)-sided disease were more likely to have BRAF WT mCRC (91% vs 71%), an ECOG performance status of 0 (56% vs 43%) and liver+other metastases (53% vs 29%). Pts with L- vs R-sided disease had longer median (95% CI) PFS (11.2 [7.6,17.0] vs 7.2 [1.1,19.1] months) and were more likely to experience ETS ≥30% (53% vs 29%). ORR (60% vs 57%), median (95% CI) duration of response (DoR; 13.2 [9.3,47.7] vs 14.3 [3.5,17.3] months), median DpR (61% vs 60%), and resection rates (any: 13% vs 14%; R0: 7% vs 14%) were similar for L- and R-sided pts. ETS ≥30% was associated with improved PFS irrespective of PTL (HR [95% CI] vs ETS < 30%: 0.53 [0.22,1.29] on L; 0.35 [0.03,3.54] on R). Conclusions: These post-hoc data are in line with larger previous studies suggesting improved ETS/PFS with Pmab treatment in RAS WT left-sided mCRC; ORR, DoR and DpR were similar regardless of PTL. No formal conclusions can be drawn regarding the activity of Pmab+FOLFIRI in right-sided mCRC due to the small pt numbers, but ETS may also predict PFS benefit in right-sided disease. Clinical trial information: NCT00508404.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

scholarly journals Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653)

2019 ◽  
Vol 37 (29) ◽  
pp. 2682-2688 ◽  
Author(s):  
Sarmad Sadeghi ◽  
Susan G. Groshen ◽  
Denice D. Tsao-Wei ◽  
Rahul Parikh ◽  
Amir Mortazavi ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Median Number ◽  
Final Report ◽  
Curative Surgery ◽  
Metastatic Urothelial Carcinoma

PURPOSE Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program–sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population. METHODS Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%. RESULTS Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each). CONCLUSION Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.

scholarly journals Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group

2019 ◽  
Vol 11 ◽  
pp. 175883591987112 ◽  
Author(s):  
Changhoon Yoo ◽  
Hyeon-Su Im ◽  
Kyu-pyo Kim ◽  
Do-Youn Oh ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Real World ◽  
Performance Status ◽  
Objective Response ◽  
Real Life ◽  
Progression Free Survival ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Liposomal Irinotecan

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice. Methods: This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea. Results: From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%). Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.

KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS504-TPS504 ◽  
Author(s):  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Masatoshi Kudo ◽  
Stephen L. Chan ◽  
Richard S. Finn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Previously Treated

TPS504 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.

Randomized open-label study of M7824 versus pembrolizumab as first-line (1L) treatment in patients with PD-L1 expressing advanced non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9114-TPS9114 ◽  
Author(s):  
Myung-Ju Ahn ◽  
Fabrice Barlesi ◽  
Enriqueta Felip ◽  
Edward B. Garon ◽  
Claudio Marcelo Martin ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Transforming Growth Factor Β ◽  
Survival Duration ◽  
Open Label ◽  
Ecog Performance Status ◽  
Line Setting

TPS9114 Background: Transforming growth factor β (TGF- β) promotes tumor progression via immune- and non–immune-related processes. M7824 is an innovative first-in-class bifunctional fusion protein composed of 2 extracellular domains of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 monoclonal antibody against PD-L1. Targeting these independent and complementary pathways may restore and enhance antitumor responses. An expansion cohort of the NCT02517398 study of patients with advanced NSCLC (n = 80) treated with M7824 in the second-line setting presented at ESMO 2018 showed an objective response rate of 86% in the subgroup with high PD-L1 tumor expression at the recommended phase 2 dose (1200 mg intravenously [IV] every 2 weeks [Q2W]). Observed data support the hypothesis that M7824 may be superior to other PD-(L)1 inhibitors, including pembrolizumab, for the treatment of NSCLC. Based on the promising antitumor activity and manageable safety profile, this study will evaluate M7824 treatment in patients with advanced NSCLC in the 1L setting. Methods: Here we present a global, randomized trial comparing M7824 vs pembrolizumab in the 1L treatment of patients with metastatic NSCLC with high PD-L1 expression levels. Patients in this study must have a histologically confirmed diagnosis of advanced NSCLC with high PD-L1 expression on tumor cells (defined as either ≥80% by the Dako 73-10 pharmDx kit or ≥50% by the Dako 22C3 pharmDx kit since both assays are expected to select a similar patient population at their respective cut-offs). ECOG performance status must be 0 or 1. Patients must not have received prior systemic treatment for advanced NSCLC. Patients with tumors with actionable mutations (for which targeted therapy is locally approved) are not eligible. Patients will receive 1200 mg Q2W or pembrolizumab 200 mg Q3W as an IV infusion until confirmed disease progression, unacceptable toxicity, or trial withdrawal. Dual primary endpoints are progression-free survival and best overall response; key secondary endpoints include overall survival, duration of response, and safety. Estimated enrollment is 300 patients. Clinical trial information: NCT03631706.

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