X versus XELOX versus PF in definitive concurrent chemoradiotherapy (DCRT) for local advanced squamous esophageal cancer (ESCC): Update from a multicenter, open-label, randomized III trial, CRTCOESC trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4531-4531
Author(s):  
Ruinuo Jia ◽  
Tanyou Shan ◽  
Lixin Wan ◽  
Anping Zheng ◽  
Shuang Hui ◽  
...  
Keyword(s):  
Concurrent Chemoradiotherapy ◽  
Clinical Stage ◽  
Intensity Modulated Radiation Therapy ◽  
Open Label ◽  
Standard Regimen ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Local Advanced ◽  
Clinical Trial Information

4531 Background: PF (5-fluorouracil plus cisplatin) is the standard regimen for local advanced ESCC with DCRT. CRTCOESC aims to evaluate the effect and safety of X (capecitabine) regimen versus XELOX (capecitabine plus oxaliplatin) and PF in Chinese local advanced ESCC with DCRT by randomized, open-label, multicenter designed. Methods: Patients with ESCC (T2-4N0-2M0) were randomized to 3 groups as X (capecitabine 625mg/m2, bid d1-5, 6 weeks), XELOX (oxaliplatin: 65mg/m2, d1, 8, 22, 29; capecitabine: 625mg/m2, bid d1-5; 6 weeks), or PF (cisplatin: 75mg/m2 d1, 29, 5-Fu: 750mg/m2 CIV24h d1-4, d29-32), Intensity Modulated Radiation Therapy (IMRT) was delivered by 50Gy/2Gy currently. In addition, quadratic randomize were done within all groups to decide whether 2 cycles chemotherapy adding or not after DCRT. 2-year OS and Grade 3-5 AEs were the primary endpoints, 2-year PFS and short-term efficacy (STE) as rates of CR and ORR (CR+PR+SD) (confirmed by gastroscopy biopsy at 16 weeks) were the secondary endpoints. Results: 244 pts successfully were accrued from 13 centers during 2014.10-2020.1. 209 pts were finished DCRT and 193 were evaluated STE at 16 weeks. 192 and 147 pts were followed up for 1- and 2- years respectively. There were no differences between 3 groups on patients’ baseline characters including age, gender, ECGO score, clinical stage, pathology grade and smoking. In X, XELOX and PF groups, the 2-year OS were 63.8% (30/46), 61.5% (32/52) and 62.5% (30/49) ( P = 0.973), the median OS were 39.7 (6.567), 40 (5.195) and 34 (5.736) (months, P = 0.703); the incidences of AEs (grade 3-5) were 26.5% (18/68), 33.8% (25/74) and 49.3% (33/67) ( P = 0.0193); the 2-year PFS were 54.3% (25/46), 53.8% (28/52) and 51% (25/49) ( P = 0.939), the median PFS were 29.06 (6.124), 17.4 (8.745) and 24.833 (6.777) (months, P = 0.811); the CR rate were 43.8% (28/64), 41.4% (29/70), and 42.4% (25/59) ( P = 0.964), and the ORR were 85.6%, 88.6%, and 96.6% ( P = 0.119), respectively. There were no differences on OS, PFS and rates of CR and ORR between 3 groups but the incidence of AEs in X group was the lowest significantly. Subgroup analysis results shown adding 2 cycles chemotherapy after CRT had both OS and PFS advantages but lacked statistically significance. Conclusions: Compared with PF, DCRT with X or XELOX shown lower incidence of AEs and similar OS, PFS and STE. X regimen carried out the lowest AEs incidence. Adding 2 cycles chemotherapy after DCRT seemly had advantages on OS and PFS. Clinical trial information: NCT02025036 .

Different safety profiles of first-line bendamustine-rituximab (BR), R-CHOP, and R-CVP in an open-label, randomized study of indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL): The BRIGHT study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8565-8565 ◽  
Author(s):  
David MacDonald ◽  
Richard van der Jagt ◽  
John M. Burke ◽  
Brad S. Kahl ◽  
Peter Wood ◽  
...  
Keyword(s):  
Remission Rate ◽  
Drug Hypersensitivity ◽  
Randomized Study ◽  
First Line ◽  
Open Label ◽  
Standard Regimen ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell ◽  
Grade 3 ◽  
Clinical Trial Information

8565 Background: The BRIGHT study demonstrated that first-line BR was non-inferior to R-CHOP/R-CVP in terms of complete remission rate in indolent NHL and MCL. This is the first detailed analysis of the safety and tolerability of the study regimens. Methods: Patients were preselected for R-CHOP or R-CVP, and then randomized to 6-8 cycles of BR (28-d cycle) or the preselected standard regimen (21-d cycles). BR dosing was bendamustine 90 mg/m2/d as a 30-min infusion on days 1 and 2 plus rituximab 375 mg/m2given before bendamustine on day 1. Colony stimulating factors (CSFs) and antiemetics were given per local standards. Results: In patients preselected for R-CHOP, 103 received BR and 98 R-CHOP. In patients preselected for R-CVP, 118 received BR and 116 R-CVP. For all regimens, ≥ 88% of patients received the planned 6 cycles. Main differences in adverse events (AEs), all grades, are shown in the Table. Incidence of grade 3/4 AEs was 69% for R-CHOP vs 56% BR, and 50% for R-CVP vs 56% BR. Grade 3/4 drug hypersensitivity, neuropathy, and rash were infrequent. Antiemetic use was similar between groups except use of aprepitant as an adjunct to 5-HT3 antagonists was higher with R-CHOP (23% [19% in cycle 1]) than BR (9% [2%]) or R-CVP (3% [2%]). CSF use was higher with R-CHOP (61%) than BR (29%) or R-CVP (27%). Analyses of event prevalence over the treatment period and by region will also be presented. Conclusions: BR, R-CHOP, and R-CVP have significantly distinct AE profiles. More nausea, vomiting, and hypersensitivity occurred with BR while more constipation, neuropathy, and alopecia occurred with RECHOP/R-CVP. Support: Teva BPP R&D, Inc. Clinical trial information: NCT00877006. [Table: see text]

A phase I, open-label, nonrandomized, pharmacokinetic study of trifluridine/tipiracil (TAS-102) in Chinese patients with solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14079-e14079
Author(s):  
Xicheng Wang ◽  
Jianfeng Zhou ◽  
Yan Li ◽  
Yuping Ge ◽  
Yanping Zhou ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase 1 ◽  
Chinese Patients ◽  
Open Label ◽  
Significant Difference ◽  
Inactive Metabolite ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Experienced Grade ◽  
Clinical Trial Information

e14079 Background: Trifluridine/tipiracil (TAS-102) is an oral combination of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and the thymidine phosphorylase inhibitor, tipiracil (TPI). Trifluridine/tipiracil is demonstrated as a valid treatment choice for Asian and Western patients (pts) with metastatic colorectal cancer refractory or intolerant to standard chemotherapies in earlier studies. Its pharmacokinetic (PK) profile was also investigated in American and Japanese phase 1 studies, but never in Chinese pts. This study was conducted to investigate the PK profile of Trifluridine/tipiracil in a Chinese population with solid tumors. Methods: Pts who has responded poorly to existing standard treatment received Trifluridine/tipiracil (35 mg/m2/dose), orally BID, on days 1-5 and days 8-12 every 4 weeks until one of discontinuation criteria was met. Blood samples for PK analysis of FTD (the active compound), fluorothymine (FTY, inactive metabolite) and TPI were collected after single and multiple doses of Trifluridine/tipiracil on days 1 and 12 of cycle 1. The safety, tolerability, and antitumor activity of Trifluridine/tipiracil were also assessed as secondary endpoints. Results: A total of 15 pts were administered Trifluridine/tipiracil and analyzed for PKs. The PKs of FTD, FTY, and TPI in Chinese pts were comparable to those in Japanese pts. Compared with American pts, although the AUC0-t of TPI on day 12 was significantly lower in Chinese pts, the Cmax and AUC0-t of FTD were not significantly different. Thirteen (86.7%) pts reported treatment-emergent adverse events (TEAEs), and eight (53.3%) pts experienced grade 3 TEAEs, of which anemia and fatigue were most frequently (≥10% of patients) reported. Grade 4 or 5 TEAEs were not observed. Conclusions: The PKs of Trifluridine/tipiracil in Chinese pts were comparable to those in Japanese pts. The exposure of FTD was showed without significant difference between Chinese, Japanese and American pts. Trifluridine/tipiracil was well-tolerated in Chinese pts and had the similar safety profile in comparison with previous studies. Clinical trial information: NCT02261532.

Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis (PIPAC-GA1).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Florian Struller ◽  
Philipp Horvath ◽  
Wiebke Solass ◽  
Frank Jurgen Weinreich ◽  
Alfred Konigsrainer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Peritoneal Metastasis ◽  
Low Dose ◽  
Tumor Regression ◽  
Open Label ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

99 Background: Efficacy of 2nd and 3rdline chemotherapy in recurrent gastric cancer with peritoneal metastasis (RGCPM) is limited. We assessed the feasibility, safety and activity of intraperitoneal chemotherapy as PIPAC C/D in RGCPM after > 1 line of intravenous chemotherapy. Methods: Open-label, single-arm, Phase II ICH-GCP Clinical Trial (NCT01854255) Patients were scheduled for 3 courses q42 days of low-dose PIPAC with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Primary endpoint was objective tumor response (RECIST 1.1). Secondary endpoints were safety (CTCAE 4.0), histological tumor regression (PRGS) and overall survival. Results: 25 patients were enrolled. 10/25 (40 %, ITT) patients had an OTR. Complete or major regression on histology was observed in 9/12 (75 %) patients who underwent at least 2 PIPAC cycles. Mean overall survival was 8.4 months (13.1 months in patients with PCI < 12). There were no treatment-related deaths, no grade 4 toxicity and four (16%) grade 3 toxicities. Conclusions: PIPAC C/D is well tolerated and active in patients with RGCPM. Survival is encouraging. Randomized controlled trials should now be designed. Clinical trial information: NCT01854255. [Table: see text]

SOPHIA analysis by chemotherapy (Ctx) choice: A phase III (P3) study of margetuximab (M) + Ctx versus trastuzumab (T) + Ctx in patients (pts) with pretreated HER2+ metastatic (met) breast cancer (MBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1040-1040 ◽  
Author(s):  
Santiago Escrivá ◽  
Seock-Ah Im ◽  
Fatima Cardoso ◽  
Javier Cortes ◽  
Giuseppe Curigliano ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Phase Iii ◽  
Rank Test ◽  
Test Results ◽  
Open Label ◽  
Innate And Adaptive Immunity ◽  
Antiproliferative Effects ◽  
Primary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

1040 Background: Despite advances, pretreated HER2+ MBC remains incurable with ongoing need for new therapies. Investigational M has similar HER2 binding and antiproliferative effects as T. Relative to T, M Fc engineering increases binding affinity for both variants of activating Fc receptor (FcR) CD16A and decreases affinity for inhibitory FcR CD32B, coordinately activating innate and adaptive immunity. In a Phase 3 (P3) trial, M prolonged PFS over T (Table). Second interim OS results from Sept 2019 also favor M (hazard ratio [HR], 0.89; 95% CI 0.69–1.13; nominal P=0.326). Methods: SOPHIA (NCT02492711), an open-label P3 trial, enrolled pts with HER2+ MBC after pertuzumab and 1–3 lines of prior treatment (Tx) for MBC. Randomization was 1:1 to M (15 mg/kg IV q3w + Ctx) or T (6 [8 for loading dose] mg/kg IV q3w + Ctx), stratified by met sites (≤2, >2), lines of Tx for met disease (≤2, >2), and Ctx choice, including capecitabine (Cap), eribulin (Eri), gemcitabine (Gem), or vinorelbine (Vin). Primary endpoints were central blinded PFS and OS, assessed sequentially using the stratified log-rank test. Results: Investigator chemotherapy choices and results by chemotherapy are shown in the table. Subjects receiving Eri and Gem had the lowest PFS hazards ratios (HRs), favoring M over T, although no statistical significance of individual chemotherapy subgroups was seen. There was variable toxicity among Ctx subgroups, and fewer subjects receiving Cap had Ctx related Grade 3 or higher (>=Gr 3) AEs. In this unblinded study, more subjects on M than T in all subgroups discontinued Ctx while continuing study antibody. Conclusions: In combination with chemotherapy in pretreated HER2+ MBC, M improved PFS over T. Safety was manageable in all Ctx subgroups. Differences among HRs for chemotherapy subgroups may be driven by selection bias and/or sensitivity differences. Clinical trial information: NCT02492711 . [Table: see text]

Nivolumab (nivo) + nab-paclitaxel (nab-P) + carboplatin (C) in patients (pts) with non-small cell lung cancer (NSCLC): Interim results from a multicenter phase I study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9095-9095 ◽  
Author(s):  
David Michael Waterhouse ◽  
Jonathan Wade Goldman ◽  
Ben George ◽  
Peter J. O'Dwyer ◽  
Moncy Ye ◽  
...  
Keyword(s):  
Phase I ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Metastatic Breast ◽  
Primary Endpoints ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Clinical Trial Information

9095 Background: Despite success of single-agent immune checkpoint inhibitors, an unmet therapeutic need remains in pts with NSCLC. Chemotherapy and immunotherapy may have synergistic antitumor activity, but safety and efficacy need to be established. Here, we present interim results for pts with NSCLC (Arm C) from the phase I safety trial of nivo + nab-P in pancreatic cancer (± gemcitabine), NSCLC (+ C), and metastatic breast cancer. Methods: Part 1 evaluated potential dose-limiting toxicities (DLTs) before Part 2 expansion. Chemotherapy-naive pts with histologically/cytologically confirmed stage IIIB/IV NSCLC received 4 cycles of nab-P 100 mg/m2d 1, 8, 15 + C AUC 6 d 1 + nivo 5 mg/kg d 15 of each 21-d cycle; in cycles 5+, nivo was continued as maintenance monotherapy. Primary endpoints: number of pts with DLTs (Part 1) and percentage of pts with grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (Parts 1 and 2). DLT-evaluable pts included those who received ≥ 2 complete nivo cycles and remained on study for 14 d after the last nivo dose in cycle 2, received ≥ 1 nivo dose and discontinued due to DLT before completing 2 nivo cycles, or experienced equivocal DLT after ≥ 1 nivo dose. Secondary endpoints included safety, PFS, OS, DCR, ORR, and DOR. Results: All pts (n = 22) received nab-P/C; results for nivo-treated pts (n = 20) are presented. Of the nivo-treated pts, the median age was 66 y (55% ≥ 65 y), 75% were female, 80% were white, and 70% had ECOG PS 1. More pts had adenocarcinoma (50%) than squamous cell carcinoma (35%; 10% other, 5% data pending). No DLTs reported (5 DLT-evaluable pts). Most common grade 3/4 TEAEs were neutropenia (45%) and anemia (35%). No grade 3/4 immune-related colitis or pneumonitis reported. Best ORR (RECIST v1.1) was 50% (1 CR [unconfirmed, 5%] and 9 PRs [45%]; 6 pts had SD [30%]; 4 pts had PD [20%]). Best ORR by histology: squamous, 71%; nonsquamous, 54%. Median PFS was 10.5 months (squamous, 10.5 months; nonsquamous, not evaluable). Conclusions: Results demonstrated safety of the nivo + nab-P/C combination in NSCLC with no unexpected safety signals. Preliminary efficacy results are promising. (NCT02309177) Clinical trial information: NCT02309177.

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]

Interim analysis of the AVETUXIRI Trial: Avelumab combined with cetuximab and irinotecan for treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC)—A proof of concept, open-label, nonrandomized phase IIa study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 80-80
Author(s):  
Marc Van Den Eynde ◽  
Nicolas Huyghe ◽  
Astrid De Cuyper ◽  
Isabelle Sinapi ◽  
Marie Ferrier ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Tumor Cell Death ◽  
Open Label ◽  
Stage Design ◽  
Primary Endpoints ◽  
Starting Dose ◽  
Immunogenic Tumor Cell ◽  
Secondary Endpoints ◽  
Grade 3

80 Background: Immune checkpoint inhibitors have demonstrated poor efficacy in MSS mCRC. Previous research indicate that cetuximab (anti-EGFR chimeric monoclonal antibody) could initiate, independently from RAS mutation, an immunogenic tumor cell death and mediate antitumor immune response. In this trial, we aim to explore the clinical efficacy and safety of anti-PDL1 avelumab (AVE) combined with cetuximab (CET) and irinotecan (IRI) for treatment refractory MSS mCRC. Methods: AVETUXIRI (NCT03608046) is a multicenter academic study recruiting MSS, BRAFV600E wt, mCRC patients (pts) refractory to standard treatment (fluoropyrimidine, oxaliplatin, irinotecan and anti-EGFR treatment if RAS wt tumor) in 2 cohorts (cohort A: RAS wt – cohort B: RAS mut). In both cohorts, patients receive CET (400 mg/m2 W1, 250 mg/m2 W2, 500 mg/m2/2 weeks from W3), IRI (180 - 150 mg/m2/2 weeks from W1) and AVE (10 mg/kg/2 weeks starting from W3). Primary endpoints are overall response rate (ORR), defined as partial or complete response (PR or CR) according (i)RECIST1.1, and safety. Secondary endpoints include disease control rate (DCR), PFS and OS. Based on a Simon 2-stage design for ORR in each cohort (cohort A: P0=0.15, P1=0.33 / cohort B: P0=0.09, P1=0.25 / α = 0.1, β = 0.2 in both cohorts), 10 and 13 patients are required in the first stage of cohort A and B respectively. At least 2 pts have to reach PR or CR in each cohort to allow the continuation of the trial in the 2nd stage. Results: Between Oct 2018 and Jan 2020, 23 patients (median age 62 y-old, 86.9% male 78.3% left-sided, 91.3% synchronous mCRC) have been included in the first stage of the trial. No major or unexpected safety events were observed. 21.7% (5/23) of pts presented grade 3 diarrhea, all related to IRI, with complete resolution after IRI dose reduction or interruption. A reduced starting dose of IRI (150 mg/m2) was amended (09/2019) for the last included 8 pts without any grade 3-4 diarrhea occurrence. Grade 1-2 hypothyroidism was the only immune-related side effect. 3 PR were observed in cohort A and none in cohort B. DCR was 60.0% (6/10) and 61.5% (8/13) in cohort A and B respectively. Median PFS and OS were respectively 4.2 and 12.7 months (cohort A) and 3.8 and 14.0 months (cohort B). 6 months-PFS rate was 40.0% and 38.5% in cohort A and B. 12 months-OS rate was 53.3% and 57.7% in cohort A and B. The median follow-up of patients was 9.2 months. Conclusions: The AVETUXIRI trial met its primary efficacy endpoint for RAS wt mCRC pts justifying the study continuation in cohort A (2nd stage). No PR was observed in RAS-mut cohort. Nevertheless, encouraging data of DCR, PFS and OS observed in RAS mut cohort allow the opening of a new cohort for RAS-mut mCRC (cohort C) with PFS as primary endpoint. Clinical trial information: NCT03608046.

Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9508-9508
Author(s):  
Georgina V. Long ◽  
Victoria Atkinson ◽  
Serigne Lo ◽  
Alexander David Guminski ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Braf Inhibitor ◽  
Local Therapy ◽  
Leptomeningeal Disease ◽  
Open Label ◽  
Phase 2 Study ◽  
Melanoma Brain Metastases ◽  
Secondary Endpoints ◽  
Local Brain ◽  
Clinical Trial Information

9508 Background: Preliminary data from the ABC (76 pts) and CheckMate 204 (94 pts) trials showed that nivo and nivo+ipi have activity in active melanoma brain metastases, with durable responses in a subset of pts. Here, we report updated 5-yr data from all pts enrolled on the ABC trial (NCT02374242). Methods: This open-label ph2 trial enrolled 3 cohorts of pts with active melanoma brain mets naïve to anti-PD1/PDL1/PDL2/CTLA4 from Nov 2014-Apr 2017. Pts with asymptomatic brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3Wx4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets i) that failed local therapy, ii) with neuro symptoms and/or iii) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed. The primary endpoint was best intracranial response (ICR) ≥wk12. Key secondary endpoints were IC PFS, overall PFS, OS, & safety. Results: A total of 76 pts (med f/u 54 mo) were enrolled; median age 59y, 78% male. For cohorts A, B and C: elevated LDH 51%, 58% and 19%; V600BRAF 54%, 56% and 81%; prior BRAFi 23%, 24%, 75%. Efficacy and toxicity are shown in the table. There were no treatment-related deaths. 1/17 deaths in cohort A & 4/16 in cohort B were due to IC progression only. Conclusions: Nivo monotherapy and ipi+nivo are active in melanoma brain mets, with durable responses in the majority of patients who received ipi+nivo upfront. A study of upfront ipi+nivo+/-SRS is underway (NCT03340129). Clinical trial information: NCT02374242. [Table: see text]

Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: An open-label, single-center, single-arm clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16117-e16117
Author(s):  
Jian-Xu Li ◽  
Ting-Shi Su ◽  
Xiao-Feng Lin ◽  
Yi-Tian Chen ◽  
Shi-Xiong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Radiation Therapy ◽  
Clinical Study ◽  
Cancer Staging ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Open Label ◽  
Grade 3 ◽  
Clinical Trial Information

e16117 Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: an open-label, single-center, single-arm clinical study Jian-Xu Li, Ting-Shi Su, Xiao-Feng Lin, Yi-Tian Chen, Shi-Xiong Liang, Bang-De Xiang; Guangxi Medical University Cancer Hospital, Nanning, China Abstract Research Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China. Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2019039), Guangxi, China. Background: Based on the results of recent studies, the PD-1 monoclonal antibodies have been approved to treat the patients with advanced hepatocellular carcinoma (HCC) by the FDA. Radiation therapy (RT) can enhance responsiveness to PD-1 monoclonal antibody by potential mechanisms. A phase Ⅱa study was conducted to assess the safety and the efficacy of combining RT with anti-PD-1 for patients with advanced hepatocellular carcinoma. Methods: Patients with advanced HCC were eligible. Stereotactic body radiation therapy (SBRT) were adopted, and the dose of radiation were Dt-PGTV 30-50 Gy/10fractions. Camrelizumab (200mg) were given intravenously every 3 weeks since the first day of RT until disease progression, or intolerable toxicity. Adverse events (AEs) and objective response rate (ORR) were summarized to assess the safety and efficacy. Results: From April 2020 to November 2020, 17 patients were enrolled (median age 54, range 32-69). 15 (88%) patients were male. 14 (82%) had ECOG performance score of 0. All the patients had Child-Pugh score A. 16 patients staged as Barcelona Clinic Liver Cancer staging C or China Liver Cancer staging Ⅲ. Extrahepatic metastases were identified in 11 (65%) patients. 13 (77%) patients were Hepatitis B virus infected. 15 (88%) patients had previously 2 lines or more chemotherapy. 9 (53%) patients had Alpha-fetoprotein level≥400 ng/ml. The ORR was 47%. The best response assessed by RECIST 1.1 was partial response (8 patients). Four patients had grade 3 immune-related adverse events (irAEs), including increased aspartate aminotransferase and alanine transaminase (n =1)，decreased hemoglobin (n =1)，decreased platelet count (n =1)，decreased neutrophil count (n =1). All grade 3 irAEs were mitigated with proper treatment. None treatment-related deaths occurred. Conclusions: In this study, RT combined with anti-PD-1 had an acceptable safety profile and indicated an effective treatment option in patients with unresectable HCC. Clinical trial information: NCT04193696. Clinical trial information: NCT04193696.

A randomized comparison of carboplatin/vinorelbine versus carboplatin/gemcitabine in advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7033-7033
Author(s):  
N. Helbekkmo ◽  
S. H. Sundtroem ◽  
U. Aaseboe ◽  
P. F. Brunsvig ◽  
C. L. Von Plessen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year

7033 Background: Carboplatin/vinorelbine (CV) and carboplatin/gemcitabine (CG) are novel 2-drug combinations in the treatment of NSCLC. In a randomized national multicenter phase III study in stage IIIB and IV patients (pts), we compared these regimens with respect to efficacy, toxicity and quality of life (QoL). Methods: Chemonaive pts with histologically or cytologically proven NSCLC, stage IIIB or IV and ECOG performance status (PS) 0–2 were eligible. There was no upper age limit. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2, both administered on day 1 and 8, in combination with carboplatin (Chatelut AUC 4) at day 1. Three courses were administered in 3-week cycles. QoL questionnaires were completed at baseline, before each cycle and then every 8 weeks up to one year. Primary endpoints were survival and QoL and secondary endpoints toxicity and time to progression (TTP). Stratification was done for age, stage and PS, and the planned sample size per arm was minimum 200. The analyses were performed on an intention-to-treat basis Results: From Oct 2003 through Dec 2004, 433 pts from 33 institutions were randomized to CV (n=218) or CG (n=215). Follow-up was minimum one year. There was no difference in overall survival between the two arms (p=0.89). Median survival was 7.3 vs. 6.5 months and 1-year survival 28% and 31% in the CV and CG arm respectively. TTP was significantly longer in the CG arm (p=0.006) with median TTP 4.2 vs. 3.9 months. There was significantly more grade 3–4 anemia and thrombocytopenia in the CG arm (p<0.001) and more grade 3–4 leucopenia in the CV arm (p= 0.001). More pts in the CG arm needed transfusions of blood (p=0.003) or platelets (p=0.001). There was no difference between the arms with respect to neutropenic infections (p=0.87). QoL data are still being analyzed and will be presented at ASCO. Conclusions: Overall survival was similar in the two treatment arms. In the CG arm, the median TTP was longer, but grade 3–4 toxicity requiring interventions, was more frequent when compared to the VC arm. No significant financial relationships to disclose.

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