Checkmate-040: Nivolumab (NIVO) in patients (pts) with advanced hepatocellular carcinoma (aHCC) and Child-Pugh B (CPB) status.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 327-327 ◽  
Author(s):  
Masatoshi Kudo ◽  
Ana Matilla ◽  
Armando Santoro ◽  
Ignacio Melero ◽  
Antonio Cubillo Gracian ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Group Methods ◽  
The Us ◽  
Duration Of Response ◽  
Report Data ◽  
Unacceptable Toxicity

327 Background: Pts with aHCC and CPB liver status are often excluded from clinical trials of novel therapies due to their poor prognosis (Greten British J Cancer 2005). Historical overall survival (OS) for these pts when treated with sorafenib (SOR) has ranged ≈3–5 mo in retrospective or descriptive studies (Abou-Alfa Gastrointest Cancer Res 2011; Da Fonseca Mol Clin Oncol 2015; Pressiani Ann Oncol 2013; Chiu Cancer 2012); thus, novel treatment options are needed for these pts. The PD-1 inhibitor NIVO is approved in the US, Canada, and elsewhere, most recently Australia, for SOR-treated pts with aHCC based on results from CheckMate-040 (NCT01658878) (El-Khoueiry Lancet 2017). Here we report data from the CPB cohort of CheckMate-040, the first prospective study of immunotherapy in this pt group. Methods: Pts with CPB (B7–B8) aHCC who were SOR-naïve (n = 25) or -experienced (n = 24) received NIVO 240 mg IV for 30 min Q2W until unacceptable toxicity or disease progression. Primary endpoints were objective response rate (ORR) (investigator assessed [INV], RECIST v1.1) and duration of response (DOR). Safety was assessed in all treated pts using NCI CTCAE v4.0. Results: Of 49 analyzed pts, 28 (57.1%) had vascular invasion or extrahepatic spread. During a follow-up range of 6–18 mo, INV ORR was 10.2% with 5 pts responding; disease control rate (DCR) was 55.1%. Median (m) time to response was 2.7 mo and mDOR was 9.9 mo; 2 pts had ongoing responses at data cutoff. The mOS was 7.6 mo (mOS follow-up was 7.4 mo); mOS in SOR-naïve and -treated pts was 9.8 and 7.3 mo, respectively. Treatment-related adverse events (TRAEs) were reported in 25 (51%) pts; 4 (8.2%) pts had select hepatic TRAEs. TRAEs led to discontinuation in 2 pts (4.1%). NIVO safety profile in these pts appeared comparable to cohorts of pts with CPA aHCC. Comparison data for pts with CPA aHCC and extended follow-up for pts with CPB aHCC will be presented. Conclusions: Encouraging DCR and durable responses were observed in pts with CPB aHCC treated with NIVO. AEs were manageable and did not lead to higher discontinuation compared with pts with CPA aHCC. NIVO showed promising efficacy and tolerability compared with historical data, supporting further investigation. Clinical trial information: NCT01658878.

Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
Thomas Yau ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
Anthony B. El-Khoueiry ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

4012 Background: NIVO monotherapy (mono) is approved for sorafenib (SOR)-treated pts with HCC based on data from CheckMate 040 (NCT01658878), which reported an objective response rate (ORR) of 14% and median overall survival (mOS) of 16 months (mo). This is the first report of efficacy and safety of the NIVO + IPI combination in SOR-treated pts with aHCC. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety and tolerability. Secondary endpoints included ORR (BICR per RECIST v1.1), duration of response (DOR), disease control rate (DCR), and OS. Cutoff was 25 Sep 2018. Results: 148 SOR-treated pts were randomized. Minimum follow-up for OS from last pt randomization date to data cutoff was 24 mo. At baseline: 88% had vascular invasion or extrahepatic spread, 91% had BCLC stage C, 84% discontinued SOR due to disease progression and 14% due to toxicity. Overall, ORR was 31% (7 had a complete response [CR]) with a median DOR of 17 mo; DCR was 49% and 24-mo OS rate was 40%. Pts in arm A had a mOS of 23 mo and 4 pts had a CR. The table shows additional efficacy results by arm. Overall, NIVO + IPI was well tolerated; 37% of pts had a grade 3–4 treatment-related adverse event (TRAE; most common: pruritus and rash); 5% had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + IPI led to clinically meaningful responses and had an acceptable safety profile in SOR-treated pts, with an ORR twice that of NIVO mono (31% and 14%, respectively). Pts in arm A had the most promising mOS of 23 mo. Clinical trial information: NCT01658878. [Table: see text]

scholarly journals Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Ho Yeong Lim ◽  
Ann-Lii Cheng ◽  
Yee Chao ◽  
Thomas Yau ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
The Philippines ◽  
Advanced Hepatocellular Carcinoma ◽  
Asian Patients ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Grade 3

<b><i>Introduction:</i></b> KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. <b><i>Methods:</i></b> Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. <b><i>Results:</i></b> The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6–4.1) versus 1.4 months (95% CI 1.4–2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32–0.70). The median OS was 13.8 months (95% CI 10.1–16.9) for pembrolizumab versus 8.3 months (95% CI 6.3–11.8) for placebo (HR 0.55; 95% CI 0.37–0.80). ORR was 20.6% (95% CI 13.4–29.5) for pembrolizumab versus 2.0% (95% CI 0.1–10.6) for placebo (difference: 18.5%; 95% CI 8.3–27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3–5 TRAEs, respectively. No treatment-related deaths occurred. <b><i>Conclusion:</i></b> Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.

scholarly journals The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Cao ◽  
Yi Yang ◽  
Tongguo Si ◽  
Jun Luo ◽  
Hui Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Once Daily ◽  
Free Survival ◽  
Unresectable Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Modified Recist

ObjectiveTo assess the efficacy and safety of transarterial Chemoembolization (TACE) combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma (HCC).Patients and MethodsThe data of patients with unresectable HCC administered a combination therapy with TACE and lenvatinib plus sintilimab were retrospectively assessed. Patients received lenvatinib orally once daily 2 weeks before TACE, followed by sintilimab administration at 200 mg intravenously on day 1 of a 21-day therapeutic cycle after TACE. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by the modified RECIST criteria.ResultsMedian duration of follow-up was 12.5 months (95%CI 9.1 to 14.8 months). ORR was 46.7% (28/60). Median DOR in confirmed responders was 10.0 months (95%CI 9.0-11.0 months). Median progression-free survival (PFS) was 13.3 months (95%CI 11.9-14.7 months). Median overall survival (OS) was 23.6 months (95%CI 22.2-25.0 months).ConclusionsTACE combined with lenvatinib plus sintilimab is a promising therapeutic regimen in unresectable hepatocellular carcinoma.

Nivolumab (NIVO) plus ipilimumab (IPI) combination therapy in patients (Pts) with advanced hepatocellular carcinoma (aHCC): Long-term results from CheckMate 040.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 269-269
Author(s):  
Anthony B. El-Khoueiry ◽  
Thomas Yau ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Adverse Events ◽  
Objective Response ◽  
Long Term Results ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Analysis ◽  
Term Survival ◽  
Duration Of Response ◽  
Long Term Follow Up

269 Background: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) followed by NIVO 240 mg Q2W is approved in the US for sorafenib-treated pts with aHCC based on initial results from CheckMate 040 (NCT01658878), which reported objective response rate (ORR) of 32% and median overall survival (mOS) of 22.8 months (mo).1 We present 44-mo long-term follow-up results from the CheckMate 040 NIVO+IPI cohort. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Safety and tolerability, ORR (blinded independent central review per RECIST v1.1), duration of response (DOR), disease control rate (DCR), and OS were assessed. Data cutoff was May 26, 2020. Results: 148 pts were randomized. Minimum follow-up was 44 mo. mOS remained at 22.2 mo in arm A, 12.5 mo in arm B, and 12.7 mo in arm C; 36-mo OS rates were 42%, 26%, and 30%, respectively. Durable responses were achieved across treatment arms, with DOR approaching 4 years in some cases. DCR was higher in arm A than arms B and C. In all arms, responses were observed regardless of baseline programmed death ligand 1 expression ( < 1% or ≥ 1%) or baseline alpha-fetoprotein level ( < 400 µg/L or ≥ 400 µg/L). Pts with hepatitis B or C virus (HBV or HCV) etiology had higher ORR than uninfected pts in arms B (29% vs 43% vs 9%) and C (31% vs 42% vs 0%). ORR was independent of etiology in arm A (HBV, 32%; HCV, 29%; uninfected, 31%). Additional efficacy data are in the table. There were no additional discontinuations due to treatment-related adverse events or immune-mediated adverse events (IMAEs) since the primary analysis. IMAEs were reported more frequently in arm A than arms B and C; the most common were rash, hepatitis, and adrenal insufficiency. Most IMAEs were reversible and resolved when treated using established algorithms. Conclusions: At a minimum follow-up of 44 mo, second-line NIVO1+IPI3 continued to demonstrate clinically meaningful responses and long-term survival benefit in aHCC. The safety profile was manageable and no new safety signals were identified with longer follow-up. Clinical trial information: NCT01658878. [Table: see text]

scholarly journals Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

2021 ◽  
Author(s):  
Osman Öcal ◽  
Kerstin Schütte ◽  
Juozas Kupčinskas ◽  
Egidijus Morkunas ◽  
Gabija Jurkeviciute ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Post Hoc Analysis ◽  
Y90 Radioembolization ◽  
Baseline Values ◽  
Post Hoc

Abstract Purpose To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9–8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2–4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22–7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02–4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). Conclusion IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.

Endometriumkarzinom: Kombination aus Lenvatinib und Pembrolizumab zeigt Wirksamkeit unabhängig vom Mikrosatellitenstatus

2021 ◽  
pp. 1-2
Author(s):  
Sarah Matz
Keyword(s):  
Endometrial Carcinoma ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy Analysis ◽  
Duration Of Response ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

<b>Purpose:</b> Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. <b>Methods:</b> Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST. <b>Results:</b> At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients. <b>Conclusion:</b> Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile. <b>Trial registration:</b> ClinicalTrials.gov NCT02501096.

Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study.

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA4001-LBA4001
Author(s):  
Ian Chau ◽  
Yuichiro Doki ◽  
Jaffer A. Ajani ◽  
Jianming Xu ◽  
Lucjan Wyrwicz ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Endpoints ◽  
First Results ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Previously Treated Patients

LBA4001 Background: NIVO demonstrated superior overall survival (OS) vs chemo in previously treated patients (pts) with ESCC (ATTRACTION-3). We report OS and progression-free survival (PFS) from CheckMate 648, the first global phase III study to evaluate both an immuno-oncology (I-O)/chemo combination and an I-O/I-O combination in advanced ESCC. Methods: Adults with previously untreated, unresectable advanced, recurrent or metastatic ESCC were enrolled regardless of tumor cell PD-L1 expression. Pts were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo alone. Primary endpoints for both comparisons were OS and PFS per blinded independent central review (BICR) in pts with tumor cell PD-L1 ≥ 1%. Hierarchically tested secondary endpoints included OS and PFS in all randomized pts. Results: 970 pts were randomized to NIVO + chemo, NIVO + IPI, and chemo arms (49% with tumor cell PD-L1 ≥ 1%). With 13 months (mo) minimum follow-up, NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Statistically significant PFS benefit was also observed for NIVO + chemo vs chemo (HR 0.65 [98.5% CI 0.46–0.92]; P = 0.0023) in pts with tumor cell PD-L1 ≥ 1%. PFS in NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% did not meet the prespecified boundary for significance. The objective response rate (per BICR) was 53% (NIVO + chemo), 35% (NIVO + IPI), and 20% (chemo) in pts with tumor cell PD-L1 ≥ 1% and in all randomized pts was 47%, 28%, and 27%, respectively; longer median (95% CI) duration of response was observed vs chemo for pts with tumor cell PD-L1 ≥ 1%: 8.4 (6.9–12.4), 11.8 (7.1–27.4), and 5.7 (4.4–8.7) mo and for all randomized pts: 8.2 (6.9–9.7), 11.1 (8.3–14.0), and 7.1 (5.7–8.2) mo, respectively. No new safety signals were identified (Table). Conclusions: NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety, in pts with advanced ESCC, and each represents a potential new 1L treatment option. Clinical trial information: NCT03143153. [Table: see text]

First-line (1L) avelumab treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Preliminary data from an ongoing study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9530-9530 ◽  
Author(s):  
Sandra P. D'Angelo ◽  
Jeffrey Russell ◽  
Jessica Cecile Hassel ◽  
Celeste Lebbe ◽  
Bartosz Chmielowski ◽  
...  
Keyword(s):  
Safety Profile ◽  
Response Rate ◽  
Objective Response ◽  
Durable Response ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Related Reaction ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

9530 Background: MCC is a rare, aggressive skin cancer. Avelumab is a fully human anti–PD-L1 antibody. In a phase 2 study in pts with distant mMCC who progressed after prior chemotherapy (JAVELIN Merkel 200; NCT02155647), avelumab showed a manageable safety profile and durable responses, including an objective response rate (ORR) of 31.8%, estimated 6-month durable response rate of 29%, and 6-month overall survival rate of 69%. Here, we report preliminary results from a separate cohort of pts with chemotherapy-naïve mMCC enrolled in the same study. Methods: Eligible pts with mMCC and no prior systemic treatment for metastatic disease received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 weeks (RECIST v1.1). Adverse events (AEs) were assessed by NCI CTCAE v4.0. Results: As of Dec 30, 2016, 29/112 planned pts had been enrolled. Median age was 75.0 years (range 47–87). Median treatment duration was 8.1 weeks (range 2.0–37.9). Of 16 pts with ≥3 months of follow-up, unconfirmed ORR was 68.8% (95% CI 41.3–89.0) with CR in 18.8%; confirmed ORR was 56.3% (95% CI 29.9–80.2; 1 unconfirmed PR with discontinuation). Of 25 pts with ≥6 weeks of follow-up, unconfirmed ORR was 64.0% (95% CI 42.5–82.0). All responses were ongoing at last follow-up, including in 5/5 pts with ≥6 months of follow-up (potential to confirm responses). 20/29 pts (69.0%) had a treatment-related AE (TRAE), including grade 3–4 TRAE in 5 pts (17.2%). TRAEs led to discontinuation in 5 pts (17.2%): 2 pts with infusion-related reaction, and 1 pt each with elevated AST and ALT, cholangitis, and paraneoplastic syndrome. There were no treatment-related deaths. 21/29 pts (72.4%) remain on treatment. Conclusions: In initial results from a cohort of chemotherapy-naïve pts with mMCC, avelumab was associated with early responses and a manageable safety profile, consistent with findings for second-line or later avelumab treatment in a previous cohort. These results suggest that responses mature to become durable and the use of 1L avelumab may increase the probability of response vs later-line treatment. Enrollment and follow-up in this 1L cohort are ongoing. Clinical trial information: NCT02155647.

First-line avelumab + axitinib in patients with advanced hepatocellular carcinoma: Results from a phase 1b trial (VEGF Liver 100).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4072-4072 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kenta Motomura ◽  
Yoshiyuki Wada ◽  
Yoshitaka Inaba ◽  
Yasunari Sakamoto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Study Data ◽  
Clinical Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Data Set ◽  
Phase 1B ◽  
Grade 3

4072 Background: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for treatment of advanced/metastatic (a/m) hepatocellular carcinoma (HCC). Avelumab is a human anti–PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a tyrosine kinase inhibitor selective for VEGF receptors 1/2/3. VEGF Liver 100 (NCT03289533) is a phase 1b study evaluating safety and efficacy of avelumab + axitinib in treatment-naive patients (pts) with HCC; interim results are reported here. Methods: Eligible pts had confirmed a/m HCC, ≥1 measurable lesion, a fresh or archival tumor specimen, ECOG PS ≤1, and Child-Pugh class A. Pts received avelumab 10 mg/kg IV Q2W + axitinib 5 mg orally BID until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and objective response (RECIST v1.1; modified [m] RECIST for HCC). Results: Interim assessment was performed after a minimum follow up of 6 months based on the released study data set (clinical cut-off date: Aug 1, 2018). As of the cut-off date, 22 pts (median age: 68.5 y) were treated with avelumab (median: 20.0 wk) and axitinib (median: 19.9 wk). The most common grade 3 treatment-related adverse events (TRAEs) (≥10% of patients) were hypertension (50.0%) and hand-foot syndrome (22.7%); no grade 4/5 TRAEs were reported. Immune-related AEs (irAEs) (≥10% of pts) were hypothyroidism (31.8%) and hyperthyroidism (13.6%). No grade ≥3 irAEs were reported; no pts discontinued treatment due to TRAEs or irAEs. Based on Waterfall plot calculations, tumor shrinkage was observed in 15 (68.2%) and 16 (72.7%) pts by RECIST and mRECIST, respectively. ORR was 13.6% (95% CI, 2.9%-34.9%) and 31.8% (95% CI, 13.9%-54.9%) by RECIST and mRECIST, respectively. OS data were immature at data cutoff. Conclusions: The preliminary safety of avelumab + axitinib in HCC is manageable and consistent with the known safety profiles of avelumab and axitinib when administered as monotherapies. This study demonstrates antitumor activity of the combination in HCC. Follow-up is ongoing. Clinical trial information: NCT03289533. [Table: see text]

Real-world (rw) clinical outcomes for advanced/metastatic non-small cell lung cancer (aNSCLC) patients (pts) treated with second line (2L) ramucirumab plus docetaxel (R+D) post frontline (1L) platinum based chemotherapy plus immune checkpoint inhibitors (Pt + ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20727-e20727
Author(s):  
Jeffrey Melson Clarke ◽  
Raina Mathur ◽  
Cliff Molife ◽  
Marta Batus ◽  
Victoria Jennifer Stefaniak ◽  
...  
Keyword(s):  
Disease Control ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Community Practice ◽  
Best Response ◽  
First Response ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response

e20727 Background: R+D is approved for use in pts with aNSCLC after Pt chemotherapy. With recent approvals, ICI can now be added to Pt chemotherapy (Pt + ICI) in 1L. This retrospective observational study provides an exploratory view of baseline characteristics and rw clinical effectiveness outcomes for pts receiving 2L R+D post 1L Pt + ICI. Methods: All adult pts treated with 2L R+D after 1L Pt + ICI therapy between 03/01/2015 and 06/30/2018, with ≥ 3 months follow up, were selected from the Flatiron Health EHR-derived de-identified database (n = 15). Rw clinical endpoints during R+D therapy included rw objective response rate (rwORR), rw disease control rate (rwDCR), rw best response, as well as Kaplan-Meier estimates of rw time to first response & rw duration of response. Results: Median age was 62 years, 10 pts (66.6%) were aged < 65 years, 11 (73.3%) were men, 3 (20.0%) had no history of smoking, 14 (93.3%) had non-squamous histology, 4 (26.7%) were EGFR positive, 3 (20.0%) were KRAS positive and 6 (85.7%) were PD-L1 negative. Of the 8 pts with a documented rw tumor response assessment, 3 (37.5%) had partial response (PR), 3 (37.5%) had stable disease (SD), & 2 (25.0%) had progressive disease as their rw best response. The rwORR (PR or complete response [CR]) & rwDCR (PR, CR, or SD) were 37.5% and 75.0%, respectively. Among responding pts, median time to first response was 2.2 months (95% CI, 1.3 - not reached [NR]) & median duration of response was 2.3 months (95% CI, 1.5 - NR). Patient numbers were too small (n = 15) and duration of follow-up was too short (3.4 months [IQR, 0.7 - 5.4]) to make robust estimation of overall survival or rw progression free survival. Conclusions: Data from this small patient cohort in US community practice are not conclusive and should be considered exploratory, but do show high rates of rw objective response and rw disease control rates during 2L R+D following 1L Pt + ICI. Data with larger sample sizes and additional follow-up are needed to better understand outcomes of R+D following the addition of ICI to 1L Pt chemotherapy regimens.

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