scholarly journals 956 Retifanlimab (INCMGA00012) in patients with recurrent MSI-H or dMMR endometrial cancer: results from the POD1UM-101 study

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A1006-A1006
Author(s):  
Dominique Berton ◽  
Patricia Pautier ◽  
Domenica Lorusso ◽  
Christine Gennigens ◽  
Laurence Gladieff ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Advanced Disease ◽  
Objective Response ◽  
Ethics Committee ◽  
Study Endpoint ◽  
Primary Study ◽  
List Type ◽  
Institutional Review ◽  
Systemic Treatments ◽  
Recurrent Endometrial Cancer

BackgroundManagement of patients with recurrent endometrial cancer after failure on platinum-based therapy remains a clinical challenge. Retifanlimab (INCMGA00012) is an investigational humanized immunoglobulin G4 monoclonal antibody against programmed cell death 1 (PD-1). We previously reported encouraging results from a preplanned interim analysis in patients with microsatellite instability-high (MSI-H) recurrent endometrial cancer treated with retifanlimab in POD1UM-101 [1]. Here, we provide top-line results from the full cohort of patients in the POD1UM-101 study.MethodsEligible patients have histologically proven, unresectable recurrent MSI-H or deficient mismatch repair (dMMR) endometrial cancer (per local testing), ECOG PS ≤1, disease progression during or following 1 to ≤5 prior systemic treatments, measurable disease (per RECIST v1.1), and are naïve to prior immune checkpoint inhibitors. MSI-H and dMMR status were centrally confirmed using PCR and IHC, respectively. Patients receive retifanlimab 500 mg every 4 weeks for up to 2 years. The primary study endpoint is safety. Confirmed best overall response and duration of response (DOR) were evaluated by independent central review (ICR) using RECIST v1.1.ResultsAs of July 6, 2021, 76 patients with centrally confirmed MSI-H (65 [85.5%]) or dMMR (11 [14.5%]) endometrial cancer had received ≥1 dose of retifanlimab; median age was 67.0 (49–88) years, 70 (92.1%) had endometrioid histology, 67 (88.2%) had metastatic disease, and 61 (80.3%) had visceral metastases. Sixty-eight (89.5%) patients had prior surgery or procedure, 54 (71.1%) patients were treated with radiotherapy, and 75 (98.7%) patients had received prior systemic therapy for advanced disease (33 [43.4%] received ≥2 prior systemic therapies for advanced disease). Median retifanlimab exposure was 7.4 (0.03–23.0) months. At data cutoff, 2 (2.6%) patients completed treatment and 30 (39.5%) were on treatment. Grade ≥3 treatment emergent AEs (TEAEs) occurred in 33 (43.4%) patients, including 10 (13.2%) with anemia and 7 (9.2%) with an immune-related AE (nephritis, n=2; autoimmune hepatitis, hepatitis, myositis, rash, and pneumonitis, n=1 each). There were no treatment-related AEs with fatal outcome. Centrally confirmed objective responses were observed in 33 (43.4%) patients (95% CI, 32.1–55.3), with 11 (14.5%) complete and 22 (28.9%) partial responses. Of the 33 patients with objective response, 25 (75.8%) had DOR for ≥6 months; median DOR was not reached. Median follow-up time for response was 8.4 (range, 1.9–28.3) months.ConclusionsRetifanlimab was well tolerated and demonstrated encouraging antitumor activity in patients with pretreated recurrent MSI-H or dMMR endometrial cancer, consistent with that achieved with other PD-1 therapies.AcknowledgementsThis study is sponsored by Incyte Corporation (Wilmington, DE).Trial RegistrationClinicaltrialsgov NCT03059823, EudraCT 2017-000865-63ReferenceBerton-Rigaud D, et al. J ImmunoTher Cancer 2020;8(Suppl 3):A164–A165 [Abstract 268].Ethics ApprovalThis study was approved by institutional review boards or independent ethics committees in Belgium (Aan de Commissie Medische Ethiek University Hospitals Leuven [CEC: S62335]; Ethics Committee of Hospital-Faculty University of Liège [LEC: 2019/48]); Bulgaria (Ethics Committee for Clinical Trials, Sofia [RA: IAL-24443/08.06.2017; CEC: КИ-80/08.06.2017]); Finland (HUS Tutkimuseettiset toimikunnat Biomedicum Helsinki [RA: KLnro 124/2019]); France (CPP Île-de-France X Hôpital, Aulnay-sous-Bois cedex [RA: MED MSA NAT-2019-08-00080; CEC: CN-RIPH 19.02.17.56415/CPP 27-2019]); Germany (Ethik-Kommission der Albert-Ludwigs-Universität Freiburg, Freiburg [RA: 3102/012; EC: 506/18]; Ethics Committee at the Technical University of Dresden, Dresden [RA: 3102/012; EC: EK 4854 AB]; Ethics Committee of the State of Berlin, Berlin [RA: 3102/012; EC: 17/0411 EK 12/15]); Italy (Comitato Etico del Policlinico Gemelli Fondazione Policlinico Universitario ”Agostino Gemelli”, Roma (RM) [no approval number issued by RA or EC]; Comitato Etico IRCCS di Candiolo, Candiolo-TO [no approval number issued by RA or EC]); Latvia (Ethics Committee for Clinical Research at Development Society of Pauls Stradins Clinical University Hospital, Riga [no approval number issued by RA or EC]); Lithuania (Lithuanian Bioethics Committee, Vilnius [no approval number issued by RA or EC]); Poland (Komisja Bioetyczna przy Uniwersytecie Medycznym, Poznań [RA: UR.DBL.474.0350.2017; CEC: 622/17]); Spain (Comité de Ética de Investigación con Medicamentos, Madrid Centro Actividades Ambulatoria [RA: 17-073 (Locator: 2VK42NE57D); CEC: 17/211]); Ukraine (Ethical Committee at Prykarpatsky Regional Clinical Oncology Center of Ivano-Frankivsk Regional Rada, Ivano-Frankivsk [no approval number issued by RA or EC]); United States (IntegReview IRB, Austin, TX [no approval number issued by IRB]; The University of Texas MD Anderson Cancer Center Institutional Review Board, Houston, TX [no approval number issued by IRB]).

403 Early results from a phase 1 study to evaluate safety, pharmacokinetics, and efficacy of AMG 404, a programmed death-1 (PD-1) antibody, in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A428-A428
Author(s):  
Timothy Price ◽  
Sant Chawla ◽  
Gerald Falchook ◽  
Hans Prenen ◽  
Iwona Lugowska ◽  
...  
Keyword(s):  
Partial Response ◽  
Solid Tumors ◽  
Clear Cell ◽  
Phase 1 ◽  
Cell Cancer ◽  
Objective Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Pharmacokinetic Parameters ◽  
Advanced Solid Tumors

BackgroundEnhancement of antitumor immunity through inhibition of the checkpoint PD-1 receptor has been effective in the treatment of many malignancies. AMG 404 is a monoclonal antibody (mAb) targeting PD-1. This phase 1, open-label, multicenter first-in-human study (NCT03853109) will evaluate the safety, tolerability, pharmacokinetics, and efficacy of AMG 404 monotherapy in adult patients with advanced solid tumors.MethodsThe primary study endpoint is dose-limiting toxicity (DLT) and safety; key secondary endpoints include pharmacokinetic parameters, objective response rate (assessed Q8W), duration of response, and progression-free survival. Key inclusion criteria include histologically or cytologically proven metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation for which standard therapies have been exhausted or not available. Prior anti-PD-(L)1 or other checkpoint inhibitors were not allowed. Five dose-finding cohorts, including 2 expansion cohorts, ranged from 3–20 patients each. AMG 404 was given until disease progression, intolerance, or consent withdrawal.ResultsAs of the data cutoff date of May 4, 2020, 62 patients received at least 1 dose of AMG 404 and were included in the safety and efficacy analysis sets. Fifty percent were men, 72% had ECOG 1 performance status, median age was 62 years (range: 28–83), and 42% had ≥3 lines of prior anticancer therapy. Median AMG 404 exposure was ~3 months (maximum: ~12 months). No DLTs were observed. Treatment-related adverse events (TRAEs) were reported for 29 patients (47%): those reported for ≥2 patients were fatigue (n=7); hypothyroidism (n=6); increased blood thyroid stimulating hormone and nausea (n=4 each); increased aspartate aminotransferase, decreased appetite, and pyrexia (n=3 each); and increased alanine aminotransferase, arthralgia, diarrhea, and increased weight (n=2 each). AEs leading to withdrawal of AMG 404 were reported for 3 patients (5%); all were serious and considered to be not related to AMG 404. Sixteen (26%) patients died on study; no deaths were considered related to AMG 404. Preliminary pharmacokinetic results were consistent with those of other therapeutic anti-PD-1 mAbs. Three patients had a confirmed partial response (pancreatic cancer, clear cell cancer, and pleomorphic sarcoma); an additional 4 patients had one scan with a partial response and are pending a confirmatory scan (clear cell renal carcinoma, undifferentiated nasopharyngeal carcinoma, sarcomatoid carcinoma of unknown primary, and colon cancer).ConclusionsAMG 404 is tolerable at the tested doses with no DLTs reported. All observed TRAEs are consistent with other anti-PD-1 therapies. Encouraging anti-tumor activity has been observed in heavily pretreated patients. The study is continuing enrollment into additional cohorts.Trial RegistrationNCT03853109Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.

Updated results of European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 1202 cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11518-11518
Author(s):  
Roberta Sanfilippo ◽  
Richard L Hayward ◽  
Jammbe Musoro ◽  
Charlotte Benson ◽  
Michael Gordon Leahy ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Dedifferentiated Liposarcoma ◽  
Study Endpoint ◽  
Primary Study ◽  
Primary Analysis ◽  
European Organization ◽  
Experimental Drugs

11518 Background: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. The most effective agents include doxorubicin, ifosfamide, trabectedin and eribulin, but, in general, objective response rates (ORR) and progression free survival (PFS) are modest. Cabazitaxel exerts its effect through inhibition of microtubular disassembly and has been shown to be relatively safe, effective and well-tolerated. EORTC 1202 assessed whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DD LPS to justify further investigation in a phase III setting. Methods: This was an international multi-center, open label single arm phase II trial. The clinical cut-off date for the primary analysis was performed on August 31, 2020. Data base lock was performed on February 2, 2021. Eligible patients with metastatic or inoperable locally advanced DD LPS, after a centralized pathological review, were treated with cabazitaxel 25mg/m² IV infusion over 1 hour every 21 days. Primary endpoint was PFS rate at 12 weeks assessed by local investigator per RECIST 1.1. Based on a Simon two-stage design, at least 4 out of 17 (Stage 1) and 11 out of 37 (Stage 2) eligible and evaluable patients who are progression-free at 12 weeks were needed. Currently, a centralized radiological assessment is ongoing. Results: Forty patients were registered by 10 institutions in 4 countries between March 2015 and March 2019, with 2 patients being ineligible. One patient was still on treatment at the clinical cut-off date. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. PFS at 12 weeks was 55% (conditional 1-sided 95% CI 40.8-100), achieving the primary study endpoint. The median FU was 21.6 months, median PFS was 6 months and median OS 21 months. RR was 8% with one CR and two PR. Twenty-three(60.5%) pts had a SD. Disease control (PR+SD) was achieved in 26 patients (68%). The most common cabazitaxel -related grade >3 adverse events in all 40 registered patients were Neutrophil count decreased (50%), febrile neutropenia (25%), fatigue (12.5%), and anemia (10%). There were no cabazitaxel-related deaths. Conclusions: EORTC 1202 met its primary endpoint, with 21/38 pts (55%) being progression-free at 12 weeks. Results of this trial confirm activity of cabazitaxel in patients with metastatic or inoperable locally advanced DD LPS and looks interesting if compared to the other available options and experimental drugs recently reported in this patient population. Clinical trial information: NCT01913652.

Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3).

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA3506-LBA3506 ◽  
Author(s):  
Volker Heinemann ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
Alexander Kiani ◽  
Ursula Vehling-Kaiser ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Duration Of Treatment ◽  
First Line Treatment

LBA3506 Background: In patients (pts) with KRAS, wild-type metastatic colorectal cancer (mCRC) a head to head comparison of anti-EGFR- and anti-VEGF-directed first-line therapy has not been reported with regard to the FOLFIRI backbone. The AIO KRK-0306 study was therefore designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in mCRC pts not pretreated for metastatic disease. Methods: Pts were randomized to FOLFIRI (Tournigand regimen) every two wks plus cetuximab (400 mg/m² day 1, followed by 250 mg/m² wkly = arm A) or bevacizumab (5 mg/kg every two wks = arm B). The intent-to-treat (ITT) population comprised all pts who had at least completed one application of therapy. While recruitment initially was independent of KRAS status, an amendment confined inclusion to KRAS wildtype (WT) tumors. Recruitment was completed in October 2012. The primary study endpoint was objective response rate (ORR, investigators read). Results: Among 735 pts of the ITT-population, KRAS-WT was identified in 592. Of these, 297 pts were randomized to arm A and 295 to arm B. Median age was 64 years, 66% of pts were male, and ECOG PS 0-1 was observed in 98% of pts. Median duration of treatment was 4.7 mo vs 5.3 mo, respectively. While in the ITT analysis, ORR was comparable in arms A vs B (62% vs 57%, odds ratio 1.249), a significant superiority was found for assessable pts in arm A. Median PFS of the ITT population was nearly identical (10.3 vs 10.4 mo, HR 1.04, p=0.69), however, overall survival (OS) showed a significantly better outcome in arm A vs arm B (28.8 vs 25.0 mo, HR 0.77, p=0.0164, 95% CI: 0.620-0.953). Sixty-day mortality was low in both arms (1.01% vs 2.71%). Conclusions: ORR was comparable between arms in the ITT analysis, but favored arm A in assessable pts. Significantly superior OS was observed in KRAS-WT patients receiving cetuximab plus FOLFIRI as first-line treatment. Clinical trial information: NCT00433927.

A randomized phase II study of cabozantinib and nivolumab versus nivolumab in recurrent endometrial cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6010-6010
Author(s):  
Stephanie Lheureux ◽  
Daniela Matei ◽  
Panagiotis A. Konstantinopoulos ◽  
Matthew Stephen Block ◽  
Andrea Jewell ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Tumor Microenvironment ◽  
Objective Response ◽  
Sample Size Calculation ◽  
Progression Free Survival ◽  
Significance Level ◽  
Immune Biomarkers ◽  
Platinum Based Chemotherapy ◽  
Elevated Liver Enzymes ◽  
Recurrent Endometrial Cancer

6010 Background: The efficacy of treatment for recurrent endometrial cancer (EC) remains limited. Vascular endothelial growth factor and inflammatory chemokines are proangiogenic factors and immune modulators involved in immune suppression. Reprogramming the tumor microenvironment by combining antiangiogenic and immunotherapy (IO) could enhance antitumor responses. Methods: A 2:1 randomized phase 2 trial compared the combination of cabozantinib and nivolumab (Arm A) versus nivolumab (Arm B) in recurrent EC. Primary endpoint was progression free survival (PFS) assessed by RECIST 1.1 (NCT03367741). Women with recurrent measurable EC were eligible. There were no limits on prior therapy, but at least one prior platinum-based chemotherapy was required. Patients (pts) were stratified according to MSI status and assessed by CT every 8 weeks. Cabozantinib was given at 40 mg daily (Arm A) and nivolumab at 240 mg, on D1 and D15 of a 28-day cycle for 4 cycles, followed by 480 mg every 4 weeks (Arms A & B). Pts with carcinosarcoma or prior IO were enrolled in an exploratory cohort and received combination treatment (Arm C). A baseline biopsy was required for all pts. CyTOF analysis was performed on fresh biopsies. Results: 76 evaluable pts were enrolled (Arm A: 36, Arm B: 18, Arm C: 9 carcinosarcoma, and 20 post IO including 7 pts crossed over from Arm B). 55% of pts had received ≥3 prior lines of therapy. Two pts were MSI high in Arm A and none in Arm B. The Kaplan-Meier estimated median PFS was 5.3 (95% CI: 3.5-9.5) months in Arm A and 1.9 (95% CI: 1.6-3.8) months in Arm B, with a log-rank p = 0.07, which met the significance level of 0.1 used for sample size calculation. Objective response rate (ORR) was 25% for Arm A and 16.7% for Arm B; stable disease (SD) was seen in 44.4% vs 11.1%, respectively. Clinical benefit (ORR+SD) was significantly higher in arm A vs B (p < 0.001). In Arm C-carcinosarcoma, one patient had a partial response (11.9 months duration) and four SD. In Arm C-prior IO, six pts responded and eight had SD. The most common related AEs in Arm A were diarrhea (47.2%), elevated liver enzymes (44.4%), fatigue (38.9%), anorexia, hypertension, and nausea (30.6%), mainly grade 1/2. Preliminary CyTOF analysis across treatment arms identified multiple immune subsets for further interrogation including activated CD8+ and CD4+ T cells. Conclusions: Cabozantinib plus nivolumab demonstrates improved PFS compared to nivolumab in heavily pre-treated women with recurrent EC. In-depth CyTOF analysis of the tumor microenvironment to identify predictive immune biomarkers of response is ongoing. Clinical trial information: NCT03367741.

ENGOT-en9/LEAP-001: A phase III study of first-line pembrolizumab plus lenvatinib versus chemotherapy in advanced or recurrent endometrial cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6106-TPS6106
Author(s):  
Christian Marth ◽  
Christof Vulsteke ◽  
Maria Jesus Rubio Pérez ◽  
Vicky Makker ◽  
Elena Ioana Braicu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Objective Response ◽  
Phase Iii ◽  
Primary Study ◽  
Antiangiogenic Agents ◽  
Newly Diagnosed ◽  
First Line ◽  
Phase Iii Study ◽  
Previously Treated

TPS6106 Background: The prognosis for endometrial cancer (EC) can be favorable when diagnosed in early stages, but prognosis and overall survival are poor in patients with advanced or recurrent EC. First-line standard of care for patients with advanced or recurrent EC is paclitaxel and carboplatin chemotherapy; however, there is a need for more effective and tolerable therapies. In the phase Ib/II trial KEYNOTE-146, which assessed the PD-1 inhibitor pembrolizumab (pembro) in combination with the multikinase inhibitor lenvatinib, an objective response rate (ORR) of 38% was observed (N=108) in patients with previously treated advanced EC. ENGOT-en9/LEAP-001 (NCT03884101) is a randomized, open-label, active-controlled, phase III study investigating pembro + lenvatinib vs chemotherapy in patients with newly diagnosed advanced or recurrent EC. Methods: Patients with newly diagnosed advanced (stage III-IV) or recurrent EC not previously treated with antiangiogenic agents; systemic chemotherapy (unless within a chemoradiation regimen); PD-1, PD-L1, or PD-L2 inhibitors; or other T-cell receptor–targeted therapies will be eligible. Patients will be randomized 1:1 to receive pembro 200 mg every 3 wk (Q3W) + lenvatinib 20 mg daily or paclitaxel 175 mg/m2 Q3W + carboplatin AUC 6 Q3W. Randomization will be stratified on the basis of proficient vs deficient mismatch repair (pMMR vs dMMR) status. The pMMR population will be further stratified by prior chemoradiation (yes vs no), measurable disease (yes vs no), and ECOG performance status (0 vs. 1). Patients will continue on treatment for up to 35 cycles of pembro vs 7 cycles of chemotherapy or until initiation of a new anticancer treatment, unacceptable adverse events, or withdrawal of consent. Primary study endpoints are progression-free survival (per RECIST v1.1 by blinded independent central review) and overall survival. Secondary study endpoints are ORR, health-related quality of life, safety and tolerability, and lenvatinib pharmacokinetics. Exploratory endpoints will include disease control rate, clinical benefit rate, and duration of response. Enrollment is ongoing. Clinical trial information: NCT03884101.

Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV no squamous non-small cell lung cancer (NSCLC) (STELLA study): Results for the primary endpoint in a confirmatory, double-blind, randomized, controlled study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21542-e21542
Author(s):  
Susana Millan ◽  
Dmytro Trukhin ◽  
Oleksii Kolesnik ◽  
Elena Poddubskaya ◽  
Andric Zoran ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Stage Iiib ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Double Blind ◽  
Study Results ◽  
Significant Difference ◽  
Secondary Endpoints

e21542 Background: MB02 is a proposed biosimilar of the reference bevacizumab. A multinational, double-blind, randomized, parallel group clinical study (STELLA) is undergoing to confirm clinical similarity between MB02 and bevacizumab in patients with stage IIIB/IV no squamous NSCLC. Methods: Subjects were randomized 1:1 to MB02 or bevacizumab (15 mg/kg) plus chemotherapy (paclitaxel [P] 200 mg/m2 and carboplatin [C] AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18) followed by MB02/bevacizumab in blinded monotherapy until disease progression, treatment intolerance, death, patient withdrawal or end of study (Week 52). As primary study endpoint, the efficacy by means of the objective response rate (ORR) evaluated by an independent radiological committee (IRC) was compared between arms at Week 18. Secondary endpoints were Progression Free Survival (PFS) and Overall Survival (OS), safety and immunogenicity (assessed at 18 and 52 weeks). Results: 627 patients were randomized: MB02 (n = 315) and bevacizumab (n = 312). Demographic and baseline characteristics were well balanced between arms. The ORR results were comparable for subjects receiving MB02 or bevacizumab plus P/C. A Risk Ratio (RR) of 1.013 (90% CI: -0.037% to 0.059) and a Risk Difference (RD) of 0.011 (90% CI: -0.037% to 0.059), were within the similarity margin predefined by FDA (0.73, 1.36) and EMA (-12%, +12%) respectively. This ORR assessed by IRC was consistent with the investigator assessment criteria. There was no significant difference between arms for secondary efficacy endpoints (PFS/OS) at week 18. Up to primary endpoint cut-off point, the safety assessment showed no significant differences between MB02 and bevacizumab arms (including the immunogenicity assessment) in terms of nature, frequency and severity of the adverse events (AE), being anaemia and hypertension the most common IMP-related AEs, with a RD between treatment groups < 5%. New signals or observable trends were no reported for MB02-treated subjects. Additional information on the secondary endpoints will be available at week 52 (end of monotherapy period). Conclusions: The statistical analysis executed for ORRs confirm the equivalence of MB02 and bevacizumab, supporting the clinical activity of MB02 treatment. MB02 was well tolerated with manageable AEs in patients with Stage IIIB/IV NSCLC. Clinical trial information: NCT03296163.

Capecitabine plus oxaliplatin (XELOX) versus bolus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for stage III colon cancer: Survival follow-up of study NO16968 (XELOXA).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 388-388 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
Josep Tabernero ◽  
Jean Alfred Maroun ◽  
Filippo G. De Braud ◽  
Timothy Jay Price ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Stage Iii Colon Cancer ◽  
Systemic Treatments ◽  
Resected Stage

388 Background: The MOSAIC trial demonstrated that adding oxaliplatin to 5-FU/LV (FOLFOX4) improved 3-year disease-free survival (DFS) compared to infusional and bolus 5-FU/LV as adjuvant therapy in patients (pts) with stage II/III colon cancer [André et al. NEJM 2004]. A significant survival advantage for FOLFOX4 versus 5-FU/LV was not evident until after median duration of follow-up had exceeded 6 years [André et al. JCO 2009]. Study NO16968 demonstrated that XELOX was superior to bolus 5-FU/LV as adjuvant therapy in pts with stage III colon cancer in terms of DFS at 57 months median follow-up (HR 0.80; 95% CI 0.69–0.93; p=0.0045) [Haller et al. JCO 2011]. The difference between treatment groups in overall survival (OS) was not significant at 59 months median follow-up (HR=0.87; p=0.1486). Data from the planned final analysis of NO16968 are presented. Methods: Pts with resected stage III colon cancer were randomized to receive XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles; 24w or Roswell Park, 4 cycles; 32w). The primary study endpoint was DFS. Secondary endpoints included OS. Results: The ITT population included 1886 pts (XELOX, n=944; 5-FU/LV, n=942). After a median follow-up of 74 months, the HR (XELOX vs 5-FU/LV) for DFS was 0.80 (95% CI 0.69–0.93; p=0.0038). Seven-year DFS rates were 63% for XELOX and 56% for 5-FU/LV. After a median follow-up of 83 months, the HR for OS was 0.83 (95% CI 0.70–0.99; p=0.0367). Absolute 7-year OS rates were 73% with XELOX and 67% with 5-FU/LV. After adjusting for stratification and prognostic variables, HRs remained essentially unchanged for both DFS (0.79; 95% CI 0.68–0.91; p=0.0016) and OS (0.84; 95% CI 0.71–1.00; p=0.0477). Locoregional / systemic treatments after recurrence were given in 230 (24%) XELOX pts and 308 (33%) 5-FU/LV pts. Conclusions: The combination of oxaliplatin and capecitabine improves OS significantly compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer after a median follow-up of 83 months; these data are comparable to those achieved with FOLFOX4 in the MOSAIC trial. XELOX is an effective adjuvant therapy option for pts with resected stage III colon cancer.

Phase II study of sorafenib combined with gemcitabine and 5-fluorouracil in patients with metastatic renal cell carcinoma: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16093-e16093
Author(s):  
L. Hongyun ◽  
C. Zhihong ◽  
Y. Xiangqing ◽  
S. Lu ◽  
C. Chuanliang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Kinase Inhibitors ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Eligibility Criteria

e16093 Background: The tyrosine kinase inhibitors sorafenib and sunitinib have been approved for use in patients with advanced RCC and have supplanted immunotherapy as first-line therapy. Nevertheless, complete responses have been observed only rarely with these agents and only 10% of patients experience PR. The vast majority of responding patients will ultimately progress despite continued therapy. In order to improve the objective response rate and the durability of those responses in patients, we conducted a single-institution, single-arm phase II trial of gemcitabine and 5-fluorouracil (5-FU) combined with sorafenib in patients with RCC. Methods: Eligibility criteria included advanced, histologically confirmed RCC; age >18 years; ECOG PS ≤ 2, adequate bone marrow, renal and hepatic function; measurable/evaluable lesions. Gemcitabine was administered at 1,000 mg/m2 over 30 min i.v. on days 1 and 8, followed by 5-FU 400 mg/m2 i.v. bolus on day 1 and 1,200 mg/m2/day × 2 days continuous infusion (28-day cycle). From day 1 of cycle 1, 400 mg sorafenib was continuously given twice daily. The sample size of 21 patients was sufficient to provide 80% power to detect an objective response rate that was greater than 10% with significance that 0.05 level. Results were expressed as mean±SD or median ± 95% CI. The primary study endpoint was objective response rate and the secondary were toxicity, progression-free survival and overall survival. Results: Patients (n = 21) were enrolled from May 2006 to Dec. 2007. The rate of objective response and disease control (including stable disease, complete responses and partial responses) were 38% (95% CI, 18–62%) and 86% (95% CI, 64–97%), respectively. Among them, there is 1 complete response and 2 pts occurred completely liquefaction deliquesce in metastatic lesions. The median PFS time is longer than 13 months, with 6/21 patients remaining progression free at 2008.12.26 the data were compiled for this report (three are longer than 26 months and there other three longer than 13 months ). The median OS time have not yet been reached, because of the amount of censoring data. Conclusions: The combination of sorafenib with gemcitabine and 5-FU shows promising activity for patients with metastatic RCC. No significant financial relationships to disclose.

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