Comparative Study cf Biosimilar Genolar® Clinical Efficacy оп the Randomized Phase III Study Results

2020 ◽  
Vol 30 (6) ◽  
pp. 782-796
Author(s):  
N. M. Nenasheva ◽  
A. V. Averyanov ◽  
N. I. Il'ina ◽  
S. N. Avdeev ◽  
G. L. Osipova ◽  
...  
Keyword(s):  
Comparative Study ◽  
Clinical Efficacy ◽  
Phase Iii ◽  
Study Results ◽  
Phase Iii Study

scholarly journals Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody DEFEND-1 Study: Results of the Randomized Phase III Study in Recent-Onset Human Type 1 Diabetes

Diabetes Care ◽  
2014 ◽  
Vol 37 (10) ◽  
pp. 2746-2754 ◽  
Author(s):  
Ronnie Aronson ◽  
Peter A. Gottlieb ◽  
Jens S. Christiansen ◽  
Thomas W. Donner ◽  
Emanuele Bosi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Type 1 Diabetes ◽  
Low Dose ◽  
Phase Iii ◽  
Recent Onset ◽  
Human Type ◽  
Study Results ◽  
Phase Iii Study ◽  
Human Type 1 Diabetes

Results of Eastern Cooperative Oncology Group Protocol E4402 (RESORT): A Randomized Phase III Study Comparing Two Different Rituximab Dosing Strategies for Low Tumor Burden Follicular Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. LBA-6-LBA-6 ◽  
Author(s):  
Brad S. Kahl ◽  
Fangxin Hong ◽  
Michael E Williams ◽  
Randy D. Gascoyne ◽  
Lynne I Wagner ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Follicular Lymphoma ◽  
Alternative Therapy ◽  
Eastern Cooperative Oncology Group ◽  
Data Monitoring Committee ◽  
Tumor Burden ◽  
Phase Iii ◽  
Cytotoxic Therapy ◽  
Study Results ◽  
Phase Iii Study

Abstract Abstract LBA-6 Background: Optimal management for low tumor burden (LTB) follicular lymphoma (FL) in the rituximab (R) era is uncertain. Historical data with watch and wait (W & W) approaches are associated with an average of 3 years to initiation of chemotherapy. We hypothesized that rituximab could delay the need for chemotherapy and that maintenance rituximab (MR) would provide disease control superior to rituximab retreatment (RR) at progression. E4402 is a randomized phase III study comparing MR and RR for patients (pt) with previously untreated, LTB (by GELF criteria) FL. Methods: Pt received R 375 mg/m2 weekly × 4 and responders were randomized to MR (single dose R q 3 mo) or RR (R weekly × 4 at disease progression). Each strategy was continued until treatment failure. The primary endpoint, time to treatment failure (TTTF), was defined as progression within 6 mo of last R, no response to R retreatment, initiation of alternative therapy, or inability to complete protocol therapy. Pt were evaluated every 3 mo, with restaging CT scans every 6 mo. The study had 81% power to detect a TTTF hazard ratio of 0.64 favoring MR. Secondary endpoints included time to first cytotoxic therapy (TTCT), quality of life (QOL) and safety. The ECOG Data Monitoring Committee recommended release of study results at a planned interim analysis in September 2011. Results: From 11/03 to 9/08, 384 with FL were enrolled. Complete or partial response was achieved in 274 pt (71%), who were then randomized to MR (n=140) or RR (n=134). Demographic features were similar in the two arms: median age 59 yr; PS 0–1 in all pt; and FLIPI low-risk (14.9 vs. 16.4%), intermediate-risk (46.3 vs. 42.9%) and high-risk (38.8 vs. 40.7%) for MR vs. RR, respectively. The mean number of R doses/pt (including the 4 induction doses) was 15.8 (range 5– 31) for MR and 4.5 (range 4–16) for RR. With a median follow-up of 3.8 yrs, TTTF was and 3.9 yr for MR vs. 3.6 yr for RR (p=NS, Fig 1). A detailed analysis of treatment failure, by type, will be presented. At 3 yrs, 95% of MR vs. 86% of RR pt (p=.027, Fig 2) remained free of cytotoxic therapy. Grade 3–4 hematologic and non-hematologic toxicities occurred in < 5% of pt; 1 death on study occurred in each Arm. At 12 months post randomization, there was no discernible difference in health related QOL and anxiety between the two arms. Conclusions: In previously untreated, low tumor burden, follicular lymphoma, no difference in TTTF for MR vs. RR was observed. Notably, the time to initiation of cytotoxic therapy was delayed in both arms compared to historical W & W strategies with similarly defined LTB FL populations. MR was slightly superior to RR for TTCT but at a cost of 3x more R. MR did not improve QOL or anxiety. In summary, RR produces outcomes comparable to MR in this patient population. Disclosures: Kahl: Genentech: Consultancy; Roche: Consultancy. Williams:Genentech: Consultancy. Gascoyne:Roche: Consultancy; Genentech: Consultancy. Horning:Genentech: Employment, Equity Ownership.

Exploratory modeling and simulation to support development of motesanib in Asian patients with non-small cell lung cancer (NSCLC) based on MONET1 study results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19103-e19103
Author(s):  
Rene Bruno ◽  
Cheng-Pang Hsu ◽  
Laurent Claret ◽  
Jianfeng Lu ◽  
Yu-Nien Sun
Keyword(s):  
Prognostic Factors ◽  
Treatment Effect ◽  
Tumor Size ◽  
Phase Iii ◽  
Smoking History ◽  
Tumor Growth Inhibition ◽  
Parameter Estimates ◽  
Asian Patients ◽  
Study Results ◽  
Phase Iii Study

e19103 Background: Motesanib failed to improve overall survival (OS) in the MONET1 phase III study when combined to carboplatin/paclitaxel (CP) vs. CP in first-line NSCLC cancer patients (JCO 30:2829-2836, 2011). However, outcome of the study was favorable in a sub-population of Asian patients. We performed exploratory modeling and simulations based on the MONET1 data in order to support further development of motesanib in Asians. Methods: We developed 1) a longitudinal tumor growth inhibition model to estimate time to tumor regrowth (TTG)) using data from 934 out of 1,090 (86%) included in MONET1 and 2) a multivariate parametric model for OS including baseline prognostic factors and tumor size metrics to capture treatment effect. OS model was assessed in simulating OS distribution and hazard ratios (HR) in multiple replicates of MONET1 and comparing 95% predictive distribution (PI) with observed data. Multiple replicates of virtual phase III studies in Asian patients were simulated to assess probability of success of alternative designs. Results: Baseline tumor size (TS) and smoking history (former and current smokers vs. never smokers) were significant independent prognostic factors for OS with Asian ethnicity and log (TTG). Logarithm of OS (in days) was defined by a linear model. Parameter estimates of the OS model are given below (Table). The model successfully predicted OS distributions and HR in the full populations and in Asian patients. Simulations suggested that a 500 patient phase III study would exceed 80% power to demonstrate motesanib combination OS superiority in Asian with an expected HR of 0.74. Conclusions: A model-based estimate of TTG captured treatment effect in Asian and simulations suggested superiority of motesanib combination in these patients. The OS model could be used to simulate expected OS based on longitudinal NSCLC tumor size data with new investigational agents and support development decisions and study design. [Table: see text]

Frontline flumatinib versus imatinib in patients with chronic myeloid leukemia in chronic phase: Results from the China randomized phase III study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7004-7004
Author(s):  
Zhang Li ◽  
Li Meng ◽  
Yanli Zhang ◽  
Huanling Zhu ◽  
Jiuwei Cui ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Phase Iii ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Primary Endpoints ◽  
Study Results ◽  
Frontline Treatment ◽  
Phase Iii Study

7004 Background: Flumatinib (FM), a derivative of imatinib (IM), is a novel BCR-ABL1 tyrosine kinase inhibitor (TKI). The aim of this open-label phase III study was to validate the efficacy and safety of FM in comparison with IM as frontline treatment in Chinese patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CML-CP). Methods: Randomization was stratified by Sokal score with a 1:1 allocation to each arm. Primary endpoints were major molecular response (MMR = BCR-ABL IS≤0.1%) rates at 6 and 12 months. Molecular responses were assessed at a central laboratory blinded to treatment allocations during the study. Efficacy endpoints were analyzed for the intention-to-treat populations. This study is registered with ClinicalTrials.gov, number NCT02204644. Results: 400 eligible patients were randomized and patient characteristics at baseline were similar in each arm. The full analysis set (FAS) consisted of 393 patients who received FM 600 mg (n = 196) or IM 400 mg (n = 197) tablets once daily. Compared with IM, FM resulted significantly higher induction of MMR rate (%; 95%CI) at 6 month (33.7; 27.06-40.29 vs 18.3; 12.88-23.67; P = 0.0005) and 12 month (48.5; 41.47-55.47 vs 33.0; 26.43-39.56; P = 0.0021) and also at 3 month (8.2; 4.33- 12.00 vs 2.0; 0.06-4.00; P = 0.0058). Significantly more patients in the FM than in the IM arm achieved a complete molecular response (BCR-ABL IS≤0.0032%) at 12 months. Early molecular response (BCR-ABL IS ≤ 10%) at 3 months and early CCyR at 6 months were also significantly higher with FM than IM (82.1; 76.78-87.50 vs 53.3; 46.33-60.27; P < 0.0001 and 60.71; 53.88-67.55 vs 49.75, 42.76, 56.73; P = 0.0332). FM has a safety profile similar to IM. The rates of grade 3/4 TEAEs of FM were similar to IM, 56.57% (112 of 198) vs 41.38% (87 of 196). However, the frequencies of some nonhematological and hematological adverse events were significantly lower in the FM than in the IM arm, such as rash (4.59% vs 12.63%, P = 0.0064) and eyelid edema (0.51 vs 14.65, P < 0.0001); leukopenia (30.61 vs 62.63, P < 0.0001) and neutropenia (30.10 vs 59.60, P < 0.0001). No specific TEAE was identified in each arm. Conclusions: This phase III study met its primary endpoints. Our study results suggest that FM is comparable to IM in its safety and superior in its efficacy profile at 3, 6 and 12 month time points. These results support FM as a frontline treatment option for patients with newly diagnosed CML-CP. Clinical trial information: NCT02204644.

Results of Eastern Cooperative Oncology Group Protocol E4402 (RESORT): A Randomized Phase III Study Comparing Two Different Rituximab Dosing Strategies for Low Tumor Burden Follicular Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. LBA-6-LBA-6 ◽  
Author(s):  
Brad S. Kahl ◽  
Fangxin Hong ◽  
Michael E Williams ◽  
Randy D. Gascoyne ◽  
Lynne I Wagner ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Follicular Lymphoma ◽  
Alternative Therapy ◽  
Eastern Cooperative Oncology Group ◽  
Data Monitoring Committee ◽  
Tumor Burden ◽  
Phase Iii ◽  
Cytotoxic Therapy ◽  
Study Results ◽  
Phase Iii Study

Abstract LBA-6 Background: Optimal management for low tumor burden (LTB) follicular lymphoma (FL) in the rituximab (R) era is uncertain. Historical data with watch and wait (W & W) approaches are associated with an average of 3 years to initiation of chemotherapy. We hypothesized that rituximab could delay the need for chemotherapy and that maintenance rituximab (MR) would provide disease control superior to rituximab retreatment (RR) at progression. E4402 is a randomized phase III study comparing MR and RR for patients (pt) with previously untreated, LTB (by GELF criteria) FL. Methods: Pt received R 375 mg/m2 weekly × 4 and responders were randomized to MR (single dose R q 3 mo) or RR (R weekly × 4 at disease progression). Each strategy was continued until treatment failure. The primary endpoint, time to treatment failure (TTTF), was defined as progression within 6 mo of last R, no response to R retreatment, initiation of alternative therapy, or inability to complete protocol therapy. Pt were evaluated every 3 mo, with restaging CT scans every 6 mo. The study had 81% power to detect a TTTF hazard ratio of 0.64 favoring MR. Secondary endpoints included time to first cytotoxic therapy (TTCT), quality of life (QOL) and safety. The ECOG Data Monitoring Committee recommended release of study results at a planned interim analysis in September 2011. Results: From 11/03 to 9/08, 384 with FL were enrolled. Complete or partial response was achieved in 274 pt (71%), who were then randomized to MR (n=140) or RR (n=134). Demographic features were similar in the two arms: median age 59 yr; PS 0–1 in all pt; and FLIPI low-risk (14.9 vs. 16.4%), intermediate-risk (46.3 vs. 42.9%) and high-risk (38.8 vs. 40.7%) for MR vs. RR, respectively. The mean number of R doses/pt (including the 4 induction doses) was 15.8 (range 5– 31) for MR and 4.5 (range 4–16) for RR. With a median follow-up of 3.8 yrs, TTTF was and 3.9 yr for MR vs. 3.6 yr for RR (p=NS, Fig 1). A detailed analysis of treatment failure, by type, will be presented. At 3 yrs, 95% of MR vs. 86% of RR pt (p=.027, Fig 2) remained free of cytotoxic therapy. Grade 3–4 hematologic and non-hematologic toxicities occurred in < 5% of pt; 1 death on study occurred in each Arm. At 12 months post randomization, there was no discernible difference in health related QOL and anxiety between the two arms. Conclusions: In previously untreated, low tumor burden, follicular lymphoma, no difference in TTTF for MR vs. RR was observed. Notably, the time to initiation of cytotoxic therapy was delayed in both arms compared to historical W & W strategies with similarly defined LTB FL populations. MR was slightly superior to RR for TTCT but at a cost of 3x more R. MR did not improve QOL or anxiety. In summary, RR produces outcomes comparable to MR in this patient population. Disclosures: Kahl: Genentech: Consultancy; Roche: Consultancy. Williams:Genentech: Consultancy. Gascoyne:Roche: Consultancy; Genentech: Consultancy. Horning:Genentech: Employment, Equity Ownership.

Improving safety in first-line metastatic colorectal cancer (MCRC) therapy with bevacizumab: Modified FOLFOX7 versus XELOX2—Results of the induction phase of the GERCOR DREAM randomized phase III study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 670-670 ◽  
Author(s):  
Christophe Tournigand ◽  
Benoist Chibaudel ◽  
Benoit Samson ◽  
Werner Scheithauer ◽  
Gérard Lledo ◽  
...  
Keyword(s):  
Performance Status ◽  
Phase Iii ◽  
Induction Phase ◽  
First Line ◽  
Study Results ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Reduced Toxicity ◽  
Metastatic Sites ◽  
Ecog Ps

670 Background: FOLFOX7 is an oxaliplatin FOLFOX regimen without 5FU bolus, first used in the OPTIMOX1 MCRC study (Tournigand, JCO 2006). Modified (m) FOLFOX7 has a reduced dose of oxaliplatin (100 mg/m²) and has been used in the OPTIMOX2 trial (Chibaudel, JCO 2009). XELOX2 derived from the bi-weekly XELOX regimen with oxaliplatin 85 mg/m² (Scheithauer, JCO 2003). Methods: First-line induction therapy (IT) allocation was randomized in unresectable MCRC patients with performance status (PS) 0-1 between 6 cycles of mFOLFOX7 with bevacizumab (B) or 6 cycles of XELOX2 with B. Stratification criteria were: center, age, ECOG PS, number of metastatic sites and LDH level. After 3-month IT, a second randomization for maintenance therapy allocation was done in non-progressive patients between B or B-erlotinib. mFOLFOX7-B consisted in B 5 mg/kg followed by folinic acid (FA) 400 mg/m² and oxaliplatin 100 mg/m² followed by 5-flurouracil (5FU) 2,400 mg/m² 46h-infusion. XELOX2-B consisted in B 5 mg/kg followed by oxaliplatin 100 mg/m² followed by capecitabine 1,250 mg/m² twice daily for seven days. Cycles were repeated every two weeks. The objective was to compare the safety and efficacy of XELOX2-B to mFOLFOX7-B (secondary objective of the study). Results: 156 patients were randomized to mFOLFOX7-B and 154 to XELOX2-B. Medians (mFOLFOX7/XELOX2) were: PFS 7.9/8.7 months (HR 0.98, CI 0.74-1.31; p=0.918), OS 26.6/23.4 months (HR 1.24, CI 0.98-1.59; p=0.075). RR (mFOLFOX7/XELOX2) was 50.0%/49.3%. Main grade 3/4 toxicities (mFOLFOX7/XELOX2) were neutropenia 9.2%/2.6% (p=0.018), diarrhea 5.2%/18.3% (p<0.001), asthenia 2.6%/11.8% (p=0.003), all 27.5%/37.6% (p=0.068). Conclusions: Both regimens have the same activity as the parent regimens with a reduced toxicity, especially mFOLFOX7-B. These regimens could be good backbones for future combinations with other agents and are well suited for frail and elderly patients. Clinical trial information: NCT00265824.

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