Efficacy and safety of capecitabine plus oxaliplatin (XELOX) as the perioperative treatment of patients with potentially resectable liver-only metastases from colorectal cancer: A single arm, open-label, multicenter phase II trial (ML22298; NCT00997685).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 777-777
Author(s):  
Feng Lin ◽  
Guoxin Li ◽  
Zhonghua Chu ◽  
Chunyi Hao ◽  
Mingqing Chen ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Open Label ◽  
Free Survival ◽  
Perioperative Treatment ◽  
Post Operation ◽  
Secondary Endpoints ◽  
Tumor Remission

777 Background: Surgical resection can improve survival of patients with resectable colorectal liver metastases (CLMs). Here, we investigatedthe efficacy and safety of XELOX as perioperative treatment for patients with potentially resectable CLM. Methods: Patients with potentially resectable liver-only metastases from CRC were enrolled. The primary endpoint of this study was progression-free survival (PFS); and the secondary endpoints included objective response rate (ORR), R0 resection rate, overall survival (OS) and safety profile of perioperative treatment of XELOX. Eligible patients were treated with XELOX (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1,000 mg/m2 b.i.d. for 14 days every 3 weeks). Tumor remission was assessed by CT after 6 weeks (2 cycles) of chemotherapy. Resectability of CLM was assessed by CT after 12 weeks (4 cycles) of chemotherapy. Adjuvant chemotherapy using XELOX was started within 8 weeks after hepatectomy. Results: Thirty patients (17 males and 13 females) were enrolled from 10 medical sites between January 2010 and October 2011, with median age of 57.5 years (range: 32-77). Median PFS was 336 days (95% CI: 173~385), and median OS was 912 days (95% CI: 516~1332). The ORR was 40% (12/30). The conversion rate from unresectable to resectable was 43.3% (13/30). Among these 11 patients who had received surgery (2 had withdrawn consent), 10 (90.9%) had received R0 resection. Subgroup analysis shows that patients who had received hepatectomy had longer median PFS [95% CI] (382 days [210~518] vs. 173 days [111~337], p = 0.0268) and median OS [95% CI] (1332 [721~NA] vs. 516 [295~1046], p = 0.005). There were 4 patients with post-operation complications of ascites and/or hydrothorax, and 3 patients had early chemotherapy termination due to drug-related AEs, including leukopenia, hepatotoxicity and diarrhea. Conclusions: Perioperative chemotherapy of XELOX is an option for patients with potentially resectable CLM due to the effect in prolonging PFS and OS, as well as the manageable toxicities and post-operation complications. Clinical trial information: NCT00997685.

Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): A randomized, open-label phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5001-5001 ◽  
Author(s):  
Amit M. Oza ◽  
David Cibula ◽  
Ana Oaknin ◽  
Christopher John Poole ◽  
Ron H.J. Mathijssen ◽  
...  
Keyword(s):  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3

5001 Background: The oral PARP inhibitor olaparib has shown antitumor activity in pts with SOC. Our multicenter study compared the efficacy of (Arm A) olaparib capsules plus P/C for 6 cycles then maintenance olaparib monotherapy vs (Arm B) P/C alone for 6 cycles and no further therapy in pts with PSR SOC (NCT01081951). Methods: Pts received 6 x 21-day(d) cycles of olaparib (200 mg bid, d1–10/21) + P (175 mg/m2 iv, d1) + C (AUC4 iv, d1), then olaparib monotherapy as maintenance (400 mg bid, continuous) (Arm A), or 6 x 21d cycles of P (175 mg/m2 iv, d1) + C (AUC6 iv, d1) then no further therapy (Arm B), until progression. Randomization (1:1) was stratified by number of platinum treatments and platinum-free interval. Primary endpoint: progression-free survival (PFS) by central review (RECIST 1.1). Secondary endpoints: overall survival (OS), objective response rate (ORR), safety. Archival tissue was collected where available for analysis of biomarker correlation. Results: Of 162 pts randomized (n=81 per arm), 156 received treatment (Arm A, n=81; Arm B, n=75) and 121 began the maintenance/no further therapy phase (Arm A, n=66; Arm B, n=55). Olaparib + P/C (AUC4) followed by maintenance olaparib showed a significant improvement in PFS vs P/C (AUC6) alone (HR = 0.51, 95% CI 0.34, 0.77; P=0.0012; median = 12.2 vs 9.6 months). OS data are immature (total events: 14%). ORR was similar for Arm A and Arm B (64 vs 58%). Most common AEs during the combination phase were alopecia (74 vs 59%), nausea (69 vs 57%) and fatigue (64 vs 57%) for Arm A vs Arm B, respectively. Pts with grade ≥3 AEs (65 vs 57%), serious AEs (SAEs: 15 vs 21%) and AEs leading to treatment discontinuation (19 vs 16%) were similar for Arm A vs Arm B. Most common AEs during maintenance/no further therapy were nausea (50 vs 6%) and vomiting (29 vs 7%). 29 vs 16% of pts had grade ≥3 AEs, 9 vs 7% had SAEs and 8% vs N/A discontinued due to AEs in the olaparib vs no treatment arms, respectively. There were no fatal AEs. Conclusions: In pts with PSR SOC, olaparib plus P/C (AUC4) followed by olaparib 400 mg bid monotherapy maintenance treatment resulted in a significant improvement in PFS vs P/C (AUC6) alone.

A randomized, open-label phase II study of nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated metastatic pancreatic adenocarcinoma (mPAC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS482-TPS482 ◽  
Author(s):  
Andrew Dean ◽  
Li-Tzong Chen ◽  
Ramesh K. Ramanathan ◽  
Sarah Blanchette ◽  
Bruce Belanger ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
Secondary Endpoints

TPS482 Background: Two combination chemotherapy regimens have emerged as standard of care options for first-line treatment of mPAC: 5-fluorouracil (5-FU)/leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX), and nab-paclitaxel + gemcitabine. Nal-IRI (MM-398) is a nanoliposomal formulation of irinotecan. In a randomized phase 3 study (NAPOLI-1), of patients with mPAC who had been previously treated with gemcitabine-based therapy, nal-IRI + 5-FU/LV demonstrated its safety and significant clinical activity, increasing overall survival (OS) and progression-free survival (PFS) relative to 5-FU/LV. The goal of this current study is to determine the preliminary safety and efficacy of nal-IRI+ + 5-FU/LV with or without oxaliplatin as compared to nab-paclitaxel + gemcitabine in previously untreated patients with mPAC. Methods: This open-label, phase 2 comparative study will be conducted in two parts. Part 1 is a safety run-in of a nal-IRI+5-FU/LV + oxaliplatin regimen. The safety run-in will enroll small cohorts of patients following a traditional 3 + 3 dose escalation design to confirm the target dose of oxaliplatin (n = ~6-18). The primary objective of Part 1 is the safety and tolerability of nal-IRI + 5FU/LV + oxaliplatin. Part 2 is a randomized, efficacy study of a nal-IRI + 5-FU/LV + oxaliplatin regimen (Arm 1), the nal-IRI + 5-FU/LV combination that previously demonstrated efficacy in the NAPOLI-1 trial (Arm 2), versus a nab-paclitaxel + gemcitabine control arm (Arm 3) (n = ~156-168). The primary objective of Part 2 is to assess the efficacy of nal-IRI-containing regimens in first-line mPAC patients compared to nab-paclitaxel + gemcitabine using the progression-free survival (PFS) rate at 24 weeks as the primary endpoint. Secondary of part 1 is a PK study and Part 2 secondary endpoints will include OS, PFS, objective response rate (per RECIST, v1.1), decrease in CA19-9 levels and quality of life assessments. Clinical trial information: NCT02551991.

scholarly journals Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kuo-Chen Wei ◽  
Peng-Wei Hsu ◽  
Hong-Chieh Tsai ◽  
Ya-Jui Lin ◽  
Ko-Ting Chen ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Newly Diagnosed ◽  
Open Label ◽  
Free Survival ◽  
Asian Patients ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints

AbstractAsunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016.

Phase II study of ifosfamide, carboplatin and etoposide (ICE) in recurrent glioblastoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2066-2066
Author(s):  
T. Aoki ◽  
K. Nojima ◽  
T. Mizutani ◽  
M. Ishikawa ◽  
A. Takasu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Secondary Endpoints

2066 Background: To evaluate the efficacy and tolerability of ifosfamide, carboplatin and etoposide ( ICE ) in patients with recurrent glioblastoma. Methods: This was an open-label, single-center phase II trial. Forty-two patients with first recurrent glioblastoma after surgery, standard radiotherapy and a first-line temozolomide-based or ACNU-based chemotherapy, were enrolled.The primary endpoint was progression-free survival at 6 months ( PFS-6 ), and secondary endpoints were response rate, toxicity, and survival. Chemotherapy consisted of Ifosfamide ( 700 mg / m2 on day 1, 2 and 3 ), carbopaltin ( 100 mg / m2 on day 1 ), etoposide ( 70 mg / m2 on day 1, 2, and 3 ), every 6 weeks. Results: PFS-6 was 37 %. The median PFS was 17 weeks. Response rate was 27 %. Adverse events were generally mild ( grade 1 or 2 ) and consisted mainly of alopecia. Conclusions: This regimen is well tolerated and has activity in patients with recurrent glioblastoma. No significant financial relationships to disclose.

Phase II study of pemetrexed (Pem) and cisplatin (Cis) plus cetuximab (Cet) followed by Pem and Cet maintenance therapy in patients (Pts) with advanced nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7554-7554
Author(s):  
Gerald Schmid-Bindert ◽  
Vittorio Gebbia ◽  
Frank Mayer ◽  
Edurne Arriola ◽  
Diego Marquez-Medina ◽  
...  
Keyword(s):  
Survival Rate ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Study Drug ◽  
Progression Free Survival ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year

7554 Background: A prospective, nonrandomized, multicenter study was conducted to assess the effect of adding cet to pem and cis in pts with advanced nonsquamous NSCLC. Methods: 113 Caucasian performance status 0-1 pts received 1st line pem (500 mg/m2) and cis (75 mg/m2) on day 1 (21d cycle) for 4-6 cycles and cet (400 mg/m2 loading dose followed by 250 mg/m2) weekly. Non-progressive pts received pem 500 mg/m2 on day 1 (21d cycle) plus cet (250mg/m2 weekly) until progression. Pts received vitamin B12/folic acid and dexamethasone. Primary endpoint was objective response rate (ORR) (RECIST 1.0). Secondary endpoints were progression free survival (PFS), 1 year survival rate, translational research (TR) and safety. Results: Pts’ characteristics: median age 59.7 years, 64% male, 50% PS 0, 92% stage IV, and 78% adenocarcinoma. All pts completed ≥ 1 cycle of induction therapy and 45% and 43% completed ≥ 1 cycle of maintenance with pem and cet, respectively. ORR (n=109) was 38.5% (80% CI 32.2-45.1), all partial responses. Disease control rate (response/stable disease) was 59.6% (80% CI: 53.1-65.9). Median PFS was 5.82 months (80% CI: 4.40-6.70). One year survival rate was 0.45 (80% CI: 0.39-0.51). Significant associations were seen between high EGFR by IHC and increased PFS (cytoplasm: HR=0.46, p=0.035; membrane: HR=0.41, p=0.008), and between high nuclear TTF-1 and increased ORR (OR=7.73, p=0.021) / PFS (HR=0.21, p<0.001) / OS (HR=0.25, p=0.035). Of 113 pts evaluated for safety, 73 (64.6%) pts had drug related CTC Grade 3/4 adverse events (AE): most frequent were neutropenia (14.2%), rash (15%), and vomiting (8.8%). Drug related serious AEs were reported in 27.4% pts: most frequent were anemia (5.3%), neutropenia (5.3%), vomiting (3.5%), and rash, renal failure, diarrhea and fatigue (1.8% each). There were 2 potential on-study drug related deaths (sudden death and large intestinal perforation). Conclusions: Pem, cis and cet appeared efficacious and tolerable. These results support further evaluation in a randomized trial. The TR outcomes are hypothesis generating given the study’s size and nonrandomized nature.

SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P) with or without cetuximab (C) in recurrent or progressive non-small cell lung cancer (NSCLC) after platinum-based therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7502-7502 ◽  
Author(s):  
Edward S. Kim ◽  
Marcus A. Neubauer ◽  
Allen Lee Cohn ◽  
Lee Steven Schwartzberg ◽  
Lawrence E. Garbo ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Duration Of Response ◽  
Independent Review ◽  
Secondary Endpoints

7502 Background: SELECT investigated whether the addition of C to standard chemotherapy improved progression-free survival (PFS) in patients (pts) with recurrent or progressive NSCLC after failure of platinum-based therapy. Methods: SELECT was a multicenter, open label, randomized phase III trial. Per investigator choice, pts received either P (500 mg/m2) or D (75 mg/m2) on day 1 and then were randomized within each group to chemotherapy plus C (400/250 mg/m2) (initial/weekly) or chemotherapy alone. Therapy was given for up to six 3-week cycles; pts randomized to C continued weekly monotherapy until disease progression or unacceptable toxicity. The primary objective was PFS for PC vs. P as determined by an Independent Review Committee (IRC). Secondary endpoints included overall survival (OS), objective response rate (ORR) and duration of response (DOR) by IRC, and safety. Preplanned subgroup analyses for epidermal growth factor receptor (EGFR) staining intensity by immunohistochemistry and histology were performed. Results for PC vs. P only are presented. Results: Between Jan 2005 and Feb 2010, 938 total pts were randomized. Baseline demographics were comparable between PC (n=301) and P (n=304): median age 64 years; male 60%; Caucasian 88%; KPS 80-100/60-70 84%/16%; squamous/non-squamous 24%/76%. Median PFS (months) PC: 2.89 and P: 2.76 (hazard ratio [HR] =1.03 [95% confidence interval (CI)=0.87-1.21]; p=0.76). Median OS (months) PC: 6.93 and P: 7.79 (HR=1.01 [95% CI=0.86-1.20]; p=0.86). ORR PC: 6.6% and P: 4.3% (odds ratio =1.59 [95% CI=0.78-3.26]; p=0.20). Median DOR (months) PC: 4.17 and P: 6.93 (HR=1.58 [95% CI=0.74-3.36]; p=0.24). There were no statistical differences in efficacy based on histology or EGFR staining intensity. More drug-related AEs/SAEs were observed in the PC arm, with differences mainly attributable to skin toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. Conclusions: The addition of C to P did not improve efficacy in this pt population. Further biomarker analyses are planned. The safety profiles for C and P were consistent with existing data and no new safety signals were observed.

An open label, randomized phase III trial evaluating the treatment (tx) effects of panitumumab (pmab) + best supportive care (BSC) versus BSC in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and in WT RAS mCRC.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Tae Won Kim ◽  
Anneli Elme ◽  
Zvonko Kusic ◽  
Joon Oh Park ◽  
Anghel Adrian Udrea ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Open Label ◽  
Exon 2 ◽  
Ras Mutation ◽  
Secondary Endpoints ◽  
To Receive ◽  
Kras Exon

642 Background: An overall survival (OS) benefit in WT KRAS exon 2 mCRC was not seen with pmab monotherapy in study 20020408 possibly due to crossover of patients (pts) in the BSC arm. Retrospective analyses have indicated that other KRAS and NRAS mutations beyond KRAS exon 2 are predictive of anti-EGFR tx effects. Study 20100007 assesses the OS benefit of pmab in chemorefractory WT KRAS exon 2 mCRC and is the first phase 3 trial to prospectively evaluate pmab tx effects in WT RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC. Methods: Anti-EGFR naive pts were randomized 1:1 to receive pmab (6 mg/kg Q2W) + BSC or BSC. KRAS exon 2 and RAS mutation status of tumors were determined centrally. The primary endpoint was OS in WT KRAS exon 2 mCRC. Secondary endpoints were OS in WT RAS mCRC and progression-free survival (PFS), objective response rate (ORR), and safety in both WT KRAS exon 2 and WT RAS groups. Crossover was not permitted. Results: 377 pts with WT KRAS exon 2 mCRC were enrolled. RAS ascertainment rate was 86%. OS was significantly improved with pmab + BSC vs BSC in both WT KRAS exon 2 (HR=0.73, 95% CI=0.57-0.93, P=0.0096) and WT RAS (HR=0.70, 95% CI=0.53-0.93, P=0.0135) mCRC (results in table). Pts with mutant RAS mCRC did not benefit from pmab tx (OS HR=0.99, 95% CI=0.49-2.00). No new safety signals were seen. Conclusions: Pmabsignificantly improved OS in chemorefractory WT KRAS exon 2 mCRC. The tx effects in OS and PFS were more pronounced in those with WT RAS mCRC, further substantiating the importance of RAS testing at diagnosis to best inform the use of pmab to treat mCRC. Clinical trial information: NCT01412957. [Table: see text]

Efficacy of vemurafenib in patients (pts) with non-small cell lung cancer (NSCLC) with BRAFV600 mutation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9074-9074 ◽  
Author(s):  
Vivek Subbiah ◽  
Radj Gervais ◽  
Gregory J. Riely ◽  
Antoine Hollebecque ◽  
Jean-Yves Blay ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Braf Mutations ◽  
Open Label ◽  
Braf Inhibition ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Prior Systemic Therapy ◽  
Grade 3

9074 Background: BRAFV600 mutations occur in 1–2% of pts with NSCLC. We previously reported the efficacy of vemurafenib, a selective BRAFV600 inhibitor, in BRAF mutation-positive non-melanoma tumors (VE-BASKET study). We now present final data for the expanded NSCLC cohort. Methods: This open-label, histology-independent, phase 2 study included 6 prespecified cohorts (including NSCLC) plus one ‘all-others’ cohort. Pts received vemurafenib (960 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (RECIST v1.1). Secondary endpoints included best overall response rate, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Because the pre-specified clinical benefit endpoint was met in the initial NSCLC cohort, the cohort was expanded. ClinicalTrials.gov identifier NCT01524978. Results: Database lock was 12 Jan 2017. Of 208 pts enrolled at 25 centers worldwide, 62 pts had NSCLC: median age 65 years; 56% male; 13% had no prior systemic therapy; 50% had ≥2 prior therapies. Responses were seen in previously treated and untreated pts (Table). The most common all-grade adverse event (AE) was nausea (40%); grade 3–5 AEs included keratoacanthoma (15%) and squamous cell carcinoma of the skin (15%). Six pts discontinued vemurafenib due to AEs; two had non-treatment-related fatal AEs. Conclusions: Vemurafenib showed evidence of encouraging efficacy in pts with NSCLC with BRAFV600 mutation, with prolonged PFS in previously untreated pts; median OS was not estimable due to ongoing responses. The safety profile of vemurafenib was similar to that seen in melanoma studies. Our results suggest a role for BRAF inhibition in NSCLC with BRAF mutations. Clinical trial information: NCT01524978. [Table: see text]

A phase Ib study of abemaciclib in combination with pembrolizumab for patients (pts) with stage IV Kirsten rat sarcoma mutant (KRAS-mut) or squamous non-small cell lung cancer (NSCLC) (NCT02779751): Interim results.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Jean-Louis Pujol ◽  
Johan F. Vansteenkiste ◽  
Luis G. Paz-Ares ◽  
Vanesa Gregorc ◽  
Julien Mazieres ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Open Label ◽  
Free Survival ◽  
Phase 1B ◽  
Clinical Trial Information ◽  
Nonsquamous Nsclc

9562 Background: Abemaciclib is an orally administered, selective small molecule cyclin-dependent kinase 4 and 6 inhibitor. In preclinical models, abemaciclib induced intratumor immune inflammation and synergized with PD-1 blockade to enhance antitumor efficacy in anti-PD-L1 refractory disease. Here, we report the safety and antitumor activity of abemaciclib plus the approved NSCLC treatment pembrolizumab in 2 cohorts for pts with nonsquamous and squamous NSCLC. Methods: Eligible pts for this nonrandomized, open-label, multicohort, phase 1b study were either chemotherapy-naive with ≥ 1% tumor cell (TC) PD-L1 staining, KRAS-mut nonsquamous NSCLC (Cohort A) or had a squamous subtype and received ≤ 1 prior platinum-containing chemotherapy regimen (Cohort B) for metastatic NSCLC. Primary endpoint was safety; secondary objectives included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-five pts with NSCLC were enrolled in each cohort. Most pts (68%) in Cohort B had received 1 prior line of chemotherapy. Safety profiles observed in both cohorts were largely consistent with previous reports for abemaciclib and pembrolizumab monotherapy. Grades 3/4 AEs in Cohorts A and B, respectively, included ALT increase (6 pts [24%]/ 0 pts), diarrhea (3 pts [12%]/ 0 pts), neutropenia (3 pts [12%]/ 0 pts), and pneumonitis (3 pts [12%]/ 1 pt [4%]). Six pts in Cohort A (24%) and 2 pts in Cohort B (8%) had a confirmed partial response for a disease control rate (CR+PR+SD) of 52% and 64%, respectively. In Cohort A, the ORR in pts with strong (≥50% TC) PD-L1 staining (n = 13) was 31% vs. 17% in pts with weak (1-49% TC) PD-L1 expression (n = 12). Median PFS and OS were 7.6 months (95% CI: 1.6, NR) and 22.0 months (95% CI: 9.9, NR) in Cohort A and 3.3 months (95% CI: 1.4, 5.2) and 6.0 months (95% CI: 3.7, 13.1) in Cohort B, respectively. Conclusions: Abemaciclib plus pembrolizumab resulted in a numerical higher rate of transaminase elevations and pneumonitis. Antitumor activity was remarkable in the KRAS-mut nonsquamous NSCLC but not noticeably higher as compared to historical data for pembrolizumab monotherapy. Clinical trial information: NCT02779751 .

The efficacy and safety of lenvatinib in patients with intermediate-stage hepatocellular carcinoma: A nationwide multicenter study in Japan.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 548-548
Author(s):  
Kaoru Tsuchiya ◽  
Masayuki Kurosaki ◽  
Azusa Sakamoto ◽  
Hiroyuki Marusawa ◽  
Chikara Ogawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multicenter Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Intermediate Stage ◽  
Median Number ◽  
Observation Time ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Modified Recist

548 Background: Lenvatinib (LEN) has been used in patients with unresectable hepatocellular carcinoma (u-HCC) since Mar 2018 in Japan. We conducted a nationwide multicenter study and especially focused on the efficacy and safety in the patients with intermediate-stage u-HCC. Methods: A total of 240 patients received LEN from March 2018 at 15 sites in Japan was enrolled. Tumour assessments in accordance with modified RECIST were done using dynamic CT or MRI within 4-8 weeks and every 6-8 weeks thereafter. Results: In this study, 88 of 240 (36.7%) patients were BCLC stage B. Among them 76 (86.3%) patients received TACE before LEN and the median number of TACE was 2 (1-10). Only 4 patients were TKI experienced and other 84 (95.5%) patients received LEN as a 1st line therapy. The median pretreatment ALBI score was -2.35 and 75 (85.2%) patients were Child-Pugh A. In this cohort, 73 (83.0%) patients were beyond up-to-seven criteria and the median pretreatment AFP was 38.2 (2-12870) ng/mL. The median observation time was 8.5 months and 16 patients died. The median progression free survival was 8.7 months, and the median overall survival (OS) was not reached. Objective response rate (ORR) and disease control rate (DCR) were 48.5% and 80.3%. AFP decrease ( > 20%) after 1 month was observed in 52 (59.0%) patients. Child-Pugh B patients (n = 13) had significantly shorter OS than Child-Pugh A (p = 0.02) and median OS in Child-Pugh B patients was 8.8 months. The patients received > 6 times TACE before LEN had significantly shorter OS than patients received ≤ 6 times TACE (p = 0.02). Additional TACE was performed in 8 patients and The median time of restarting LEN was 19 days. The median ALBI score before additional TACE, Day 1 after TACE and Day 28 after TACE were -2.38, -2.07, and -2.36.There was no severe adverse event associated with additional TACE. The median duration of LEN in patients treated with LEN and additional TACE was 8.5 months. Conclusions: The ORR and DCR of LEN in Child-Pugh A patients with intermediate-stage HCC were 46.6% and 79.3%. The therapeutic strategies for intermediate-stage HCC should be discussed based on the liver function, tumor states, and treatment course about TACE.

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