Subgroup analyses of METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients (pts) with advanced renal cell carcinoma (RCC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 499-499 ◽  
Author(s):  
Bernard J. Escudier ◽  
Robert J. Motzer ◽  
Thomas Powles ◽  
Nizar M. Tannir ◽  
Ian D. Davis ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Tyrosine Kinases ◽  
Clear Cell ◽  
Clinical Activity ◽  
Time To Progression ◽  
Phase 3 ◽  
Subgroup Analyses ◽  
Baseline Characteristics ◽  
To Receive ◽  
Clinical Trial Information

499 Background: Cabozantinib (C) inhibits tyrosine kinases including VEGFRs, MET, and AXL. The METEOR phase 3 trial (NCT01865747) met its primary endpoint of significant improvement in PFS with C versus everolimus (E) in pts with advanced clear cell RCC and prior exposure to VEGFR TKIs (7.4 mo median PFS [C] vs 3.8 mo [E], HR = 0.58, 95% CI, 0.45 to 0.75; p < 0.001). The improvement in PFS was accompanied by a significant improvement in ORR and a trend for improved OS at an interim analysis. Safety profiles of C and E in this trial were similar to prior experience with each drug in this pt population. This analysis further evaluates PFS and ORR across pt subgroups. Methods: Pts had advanced RCC with clear cell component, measurable disease per RECIST 1.1, KPS ≥ 70%, and were stratified by MSKCC prognostic criteria and number of prior VEGFR TKIs. Pts must have progressed during treatment or within 6 months of the last dose of their most recent VEGFR TKI. 658 pts were randomized 1:1 to receive C (60 mg QD) or E (10 mg QD). The primary endpoint was PFS among the first 375 pts randomized. ORR was a secondary endpoint. Results: In the PFS group, 187 pts were randomized to C and 188 to E. 73% pts had 1 and 27% pts ≥ 2 prior VEGFR TKIs; 43% pts had favorable, 41% intermediate, and 15% poor risk by MSKCC criteria. Across multiple subgroups defined by baseline characteristics, PFS HRs favored C over E. PFS HRs were similar for subgroups defined by prior number of TKIs (HR = 0.56 [1 prior] and 0.67 [ ≥ 2 prior]), and showed higher activity of C over E in pts with fewer MSKCC risk factors (HR = 0.54 [0 factors], 0.56 [1 factor], 0.84 [ ≥ 2 factors]) or with metastases in various organs (HR = 0.47 [lung mets], 0.53 [liver mets], 0.50 [bone mets]). Detailed analysis of the clinical activity of C and E (PFS and ORR) across pt subgroups will be presented, including treatment duration with first VEGFR TKI ( < or ≥ 6mo), receipt of prior anti-PD1/PDL1 agents, time to progression after most recent TKI ( < or ≥ 3mo), and frequency/location of metastases. Conclusions: The METEOR trial met its primary endpoint of improved PFS, and subgroup analyses of the endpoints PFS and ORR generally favored C over E in patients with advanced RCC. Clinical trial information: NCT01865747.

Outcomes with sorafenib (SOR) followed by regorafenib (REG) or placebo (PBO) for hepatocellular carcinoma (HCC): Results of the international, randomized phase 3 RESORCE trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 344-344 ◽  
Author(s):  
Richard S. Finn ◽  
Philippe Merle ◽  
Alessandro Granito ◽  
Yi-Hsiang Huang ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Systemic Treatment ◽  
Study Drug ◽  
Locoregional Therapy ◽  
First Line ◽  
Phase 3 ◽  
Dose Time ◽  
Baseline Characteristics ◽  
To Receive ◽  
Clinical Trial Information ◽  
Radiologic Progression

344 Background: SOR is standard first-line systemic treatment for HCC unsuitable for locoregional therapy. RESORCE showed that REG improves overall survival (OS) in patients who progressed during SOR treatment (HR 0.63, 95% CI 0.50, 0.79; P < 0.001). This exploratory analysis describes outcomes for the sequence of SOR followed by REG. Methods: 573 patients were randomized 2:1 to receive REG 160 mg/day (d), 3 wks on/1 wk off or PBO. Data on prior SOR treatment and radiologic progression were prospectively collected. Efficacy and safety were evaluated by the last SOR dose. Time from the start of SOR to death was assessed. Results: Baseline characteristics were balanced. Times from the start of SOR to progression on SOR and times from progression on SOR to start of study drug were similar (Table). When analyzed based on last SOR dose 800 mg/d vs < 800 mg/d, rates of all grade treatment-emergent adverse events (TEAEs) on study were similar (REG: 100% vs 100%; PBO: 92% vs 93%). TEAE grades 3/4/5 by last SOR dose 800 mg/d vs < 800 mg/d were 52/11/15% vs 61/10/12%, respectively, with REG and 30/8/24% vs 32/7/14% with PBO. HRs (95% CI) REG/PBO for OS by last SOR dose were similar: 0.67 (0.51, 0.87) for 800 mg/d and 0.68 (0.48, 0.97) for < 800 mg/d. Median OS (95% CI) from the start of SOR was 26.0 months (22.6, 28.1) for REG and 19.2 months (16.3, 22.8) for PBO. Clinical trial information: NCT01774344. Conclusions: This exploratory subgroup analysis by prior SOR dose demonstrates a consistent survival benefit for REG. In addition, the safety profile of REG was not remarkably different when analyzed by the last SOR dose.[Table: see text]

Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced non-clear cell renal cell carcinoma (nccRCC) (HCRN GU16-260-Cohort B).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4510-4510
Author(s):  
Michael B. Atkins ◽  
Opeyemi Jegede ◽  
Naomi B. Haas ◽  
David F. McDermott ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Clear Cell ◽  
Metastatic Lesion ◽  
Limited Information ◽  
Cell Renal Cell Carcinoma ◽  
Best Response ◽  
Treatment Naïve ◽  
Correlative Studies ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information

4510 Background: The HCRN GU16-260 trial reported on the efficacy and toxicity of nivo monotherapy in treatment naïve clear cell RCC (Cohort A) and the efficacy of nivo/ipi salvage therapy in pts with tumors resistant to initial nivo monotherapy (Atkins JCO 2020.38.15_suppl.5006). Limited information is available on the effects of such an approach in pts with advanced nccRCC. Methods: Eligible pts with treatment-naïve nccRCC received nivo 240mg IV q2 wk x 6 doses followed by 360mg IV q3 wk x 4 doses followed by 480 mg q4 wk until progressive disease (PD), toxicity, or completion of 96 wks of treatment (Part A). Pts with PD prior to or stable disease (SD) at 48 wks (pSD) were potentially eligible to receive salvage nivo (3mg/kg) /ipi (1 mg/kg) q3 wk x 4 doses followed by q4 wk nivo maintenance for up to 48 wks (Part B). All pts were required to submit tissue from a metastatic lesion obtained within 12 months (mo) prior to study entry and prior to enrolling on Part B for correlative studies. Results: 35 pts with nccRCC were enrolled between 5/2017 and 12/2019 at 12 participating HCRN sites. Median age 63 (range 35-84 years); 89% male. IMDC favorable 8 (23%), intermediate 18 (51%) and poor risk 9 (26%). Of the 35 pts 19 (54%) had papillary, 6 (17%) chromophobe and 10 (29%) unclassified histology. RECIST defined ORR was 5 of 35 (14.3%) [CR 2 (5.7%), PR 3 (8.6%)], SD 16 (45.7%), PD 14 (40.0%). Immune-related ORR was 8 of 35 (22.9%). RECIST ORR by histology was: papillary - 1/19 (5%); chromophobe - 1/6 (17%); unclassified - 3/10 (30%). 9 pts (26%) had tumors with sarcomatoid features with 3 (33%) (2 unclassified, 1 papillary) responding. Median PFS was 4.0 (2.7, 4.3) mo. 21 pts remain alive. None of the responders have progressed or died. 28 pts (25 PD, 3 pSD) were potentially eligible for salvage nivo/ipi (Part B), but 12 did not enroll due to symptomatic PD (2), grade 3-4 toxicity on nivo (3), or other including no biopsy tissue (7). In the 16 Part B pts, best response to nivo/ipi was: PR (1, 6%) – (unclassified/non-sarcomatoid); SD (7, 44%); PD (8, 50%). Grade 3 Treatment-related adverse events (TrAEs) were seen in 7/35 (20%) on nivo. Grade 3-5 TrAEs were seen in 7/16 (44%) on nivo/ipi with 1 pt experiencing sudden death. Correlative studies including PD-L1 status, WES and RNAseq are pending. Conclusions: Nivo monotherapy has limited activity in treatment naïve nccRCC with most responses (4 of 5) seen in pts with sarcomatoid and/or unclassified tumors. Toxicity is consistent with prior nivo studies. Salvage treatment with nivo/ipi was provided in 16 of 28 (57%) pts with PD/pSD on nivo monotherapy, with 1 response observed. Clinical trial information: NCT03117309.

Improved transfusion independence rates for momelotinib versus ruxolitinib in anemic JAKi naïve myelofibrosis patients independent of baseline platelet or transfusion status.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19039-e19039
Author(s):  
Jean-Jacques Kiladjian ◽  
Uwe Platzbecker ◽  
Jiří Mayer ◽  
Árpád Illés ◽  
Witold Prejzner ◽  
...  
Keyword(s):  
Response Rate ◽  
Clinical Activity ◽  
Common Occurrence ◽  
Phase 3 ◽  
Double Blind ◽  
Transfusion Independence ◽  
Prognostic Importance ◽  
Clinical Trial Information ◽  
Progressive Anemia ◽  
The Continuum

e19039 Background: Momelotinib (MMB) is a potent JAK1, JAK2 and ACVR1 inhibitor with clinical activity against the hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms and splenomegaly, across the continuum of JAKi naïve or previously JAKi treated intermediate/high risk MF patients as demonstrated in the previously conducted Phase 3 SIMPLIFY-1 & -2 clinical trials (S1, S2). S1 was conducted in JAKi-naïve patients with MF (n = 432) double-blind randomized 1:1 to MMB or ruxolitinib (RUX). MMB demonstrated a statistically non-inferior splenic response rate (SRR) to RUX at the W24 landmark analysis in S1 but did not meet significance for total symptom score (TSS) response. Low SRR and TSS response was observed for RUX in patients with low platelets, while MMB elicited consistent SRR and TSS response across the platelet subsets, comparable to the response in the ITT. Transfusion independence (TI) at W24 was higher for MMB vs RUX patients across all PLT strata. Methods: Progressive anemia is a common occurrence in MF with nearly all MF patients requiring transfusions as their disease advances. Given the prognostic importance of Hgb and transfusion status in MF patients including evidence that achieving or maintaining transfusion independence by Week 24 with momelotinib is associated with improved OS in S1 and S2, we expanded the previously reported retrospective platelet subset analysis to explore the W24 TI response rates for MMB and RUX randomized patients in S1 by baseline Hgb and PLT levels and transfusion status. Results: The data presented here suggest that the prognostically-important W24 TI rate was substantively higher in anemic patients receiving MMB versus RUX, irrespective of the degree of anemia. MMB is also more effective relative to RUX in achieving or maintaining TI in JAKi naïve patients irrespective of baseline PLT count or baseline transfusion status. Conclusions: Together with data suggesting that TI response at W24 with momelotinib is associated with a survival advantage, these data further support the potential TI benefits of inhibiting ACVR1 in addition to JAK1 and JAK2 with MMB in MF patients. Clinical trial information: NCT01969838, NCT02101268. [Table: see text]

Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 234-234 ◽  
Author(s):  
Li-Tzong Chen ◽  
Daniel D. Von Hoff ◽  
Chung-Pin Li ◽  
Andrea Wang-Gillam ◽  
Gyorgy Bodoky ◽  
...  
Keyword(s):  
Sensitivity Analyses ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Prior Therapy ◽  
Previously Treated ◽  
Grade 3 ◽  
Intent To Treat ◽  
To Receive ◽  
Clinical Trial Information

234 Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506. [Table: see text]

Phase III study of lapatinib (L) plus trastuzumab (T) and aromatase inhibitor (AI) vs T+AI vs L+AI in postmenopausal women (PMW) with HER2+, HR+ metastatic breast cancer (MBC): ALTERNATIVE.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1004-1004 ◽  
Author(s):  
William John Gradishar ◽  
Roberto Hegg ◽  
Seock-Ah Im ◽  
In Hae Park ◽  
Sergei Tjulandin ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
To Receive ◽  
Clinical Trial Information

1004 Background: Combination ofHER2-targeted therapy+AI improved clinical benefit in patients (pts) with HER2+, HR+ MBC vs AI alone in two previous trials, median progression free survival (mPFS) 4.8 vs 2.4 mo (TAnDEM), and 8.2 vs 3.0 mo (EGF30008). Dual HER2 blockade enhances clinical benefit vs single HER2 blockade. This study evaluated the safety and efficacy of dual vs single HER2 blockade (L+T vs T/L)+AI in HER2+, HR+ MBC progressing on (neo)adjuvant/first-line T+chemotherapy (CT). HER2 and HR status were assessed for eligibility at local lab. Methods: PMW were randomized 1:1:1 to receive T (8mg/kg followed by 6mg/kg IV Q3W)+L (1000mg/d)+AI or T+AI or L (1500mg/d)+AI. AI was per investigator’s choice. Pts were excluded if they were intended for CT. The primary endpoint was to assess superiority of PFS with L+T vs T. Secondary endpoints included PFS (L vs T), overall survival (OS), overall response rate (ORR), and safety. Results: 369 pts were enrolled; current analysis included 355 pts (data cutoff, March 11, 2016); L+T (n = 120), T (n = 117) or L (n = 118). Final PFS data were analyzed after 137 events. Baseline characteristics were balanced across all treatment (tx) arms. The primary endpoint was met; superior PFS was observed with L+T vs T (mPFS, 11 vs 5.7 mo; HR = 0.62, 95% CI [0.45, 0.88], P= 0.0064). This benefit of L+T was consistent in key subgroups. mPFS with L vs T was 8.3 vs 5.7 mo (HR = 0.71, 95% CI [0.51, 0.98], P= 0.0361). ORR with L+T, T, and L was 32%, 14%, and 19% respectively. OS data are immature. Most common adverse events (AEs) with L+T, T and L (≥15%, any arm) were diarrhea (69%, 9%, 51%), rash (36%, 2%, 28%), nausea (22%, 9%, 22%), and paronychia (30%, 0, 15%). Hepatic abnormalities of > 3 ULN ALT/AST levels were noted in 4%, 6%, and 16% respectively. Incidence of tx-related SAEs was 5%, 2%, and 4% and on-tx deaths was 3%, 4%, and 5%, respectively. Conclusions: Dual HER2 blockade with L+T+AI showed superior PFS benefit vs T+AI, in pts with HER2+, HR+ MBC. Incidence of AEs was increased with L+T. This combination can potentially offer an effective CT-sparing tx option in subgroup of HER2+, HR+ pts without aggressive disease and who are not candidates for CT. Clinical trial information: 2010-019577-16.

Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial.

2020 ◽  
Vol 38 (18_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
Shaji Kumar ◽  
Susanna J. Jacobus ◽  
Adam D. Cohen ◽  
Matthias Weiss ◽  
Natalie Scott Callander ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Initial Therapy ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Phase 3 ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Induction Regimen ◽  
To Receive ◽  
Clinical Trial Information

LBA3 Background: Bortezomib (btz) combined with lenalidomide (len) and dexamethasone (dex) (VRd) is a standard initial therapy for NDMM. Carfilzomib (cfz), a next-generation proteasome inhibitor, in combination with len-dex (KRd) has shown higher efficacy in phase II trials. This randomized phase III trial was designed to examine if KRd improves progression free survival (PFS) compared to VRd in NDMM (current results), and whether indefinite maintenance with len improves OS compared with two-year maintenance (to be analyzed once data matures). Methods: Patients (Pts) with NDMM, were randomized to receive VRd or KRd in a 1:1 fashion for 36 weeks followed by a second randomization (1:1) to indefinite versus two years of len maintenance. Pts without del17p, t (14;16), t(14;20), plasma cell leukemia or high-risk GEP70 profile, were enrolled. VRd arm included btz 1.3 mg/m2 on days(d) 1, 4, 8, and 11 (d 1, 8 for cycles 9-12), len 25 mg d 1-14, and dex 40 mg d 1, 2, 4, 5, 8, 9, 11, 12 of a 3-week (wk) cycle for 12 cycles, while pts in the KRd arm received cfz 36 mg/m2 d 1, 2, 8, 9, 15, 16 with len 25 mg daily on d 1-21 and dex 40 mg wkly, in 4 wk cycles for 9 cycles. Maintenance included len 15mg d 1-21 every 4 wks. The study was designed to detect a hazard ratio (HR)=0.75 with 80% power at 1-sided 2.5% alpha and 399 PFS events (progression or death regardless of intervening therapy). Results: The study accrued 1087 pts (VRd=542, KRd=545). The median age was 65y. Treatment, efficacy, and toxicity data are in the table. At the second of 3 planned interim analyses, with PFS HR=1.04 (95% CI, 0.8 to 1.3, p=0.74), futility was met. Median PFS was VRd=34.4m and KRd=34.6m; no differences were seen based on age (<65 or ≥65), presence or absence of t(4;14) or ISS stage. The three-year OS (95% CI) was similar: VRd 84% (80 to 88) and KRd 86% (82 to 89). Conclusions: In this randomized phase 3 trial, KRd did not improve PFS compared with VRd in NDMM. A significantly higher rate of cardio-pulmonary and renal toxicity was observed with KRd, while neuropathy rates were higher with VRd. VRd remains the standard triplet induction regimen in standard and intermediate risk NDMM, and a suitable backbone for 4 drug combinations. Clinical trial information: NCT01863550 . [Table: see text]

scholarly journals OP0277 AURORA PHASE 3 STUDY DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 172.2-173 ◽  
Author(s):  
C. Arriens ◽  
S. Polyakova ◽  
I. Adzerikho ◽  
S. Randhawa ◽  
N. Solomons
Keyword(s):  
Primary Endpoint ◽  
Research Funding ◽  
Standard Of Care ◽  
Phase Iii ◽  
Therapeutic Drug ◽  
Phase 3 ◽  
Double Blind ◽  
Renal Response ◽  
Subgroup Analyses ◽  
And Control

Background:Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. LN occurs more frequently and is more severe in Hispanic/Latino ethnicity SLE patients. The recently completed phase 3 AURORA study builds on the favorable efficacy seen in the Phase IIb AURA-LV study in patients with active LN.Objectives:Document efficacy and safety of VCS vs placebo over one year when used with 2 grams of MMF daily and a rapid steroid taper in patients with active LN.Methods:AURORA is a Phase III multicenter, randomized, double-blind, placebo-controlled 52-week study of active LN patients. Patients were randomized 1:1 to VCS (23.7 mg BID) or placebo in combination with mycophenolate (MMF, 1 g BID) and rapidly tapered oral steroids. The primary endpoint was renal response (RR) at 52 weeks, defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of > 20%, presence of sustained, low dose steroids and no administration of rescue medication. Ethnicity subgroup analyses of RR was also undertaken given the higher severity of disease in the Hispanic/Latino LN patients.Results:There were 357 patients enrolled, 88% female, median age of 31 and 33% of Hispanic/Latino ethnicity. Renal response by intention to treat analysis at 52 weeks was 40.8% for the voclosporin arm and 22.5% for the control arm (OR: 2.65; 95% CI: 1.64, 4.27; p< 0.001); therefore, AURORA met its primary endpoint. These findings were consistent with those observed in the previously completed pivotal AURA-LV study. Ethnicity subgroup analysis of RR at 52 weeks noted benefit of VCS in both Hispanic/Latino (VCS 38.6% and control 18.6%, p=0.0062, OR 3.45) and non-Hispanic/Latino patients (VCS 41.8% and control 24.6%, p=0.0045, OR 2.29). The benefits of VCS were also seen for all pre-specified hierarchical secondary endpoints: RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) favored VCS. VCS was well tolerated with no unexpected safety signals. The overall incidence of SAEs were similar in both groups (VCS 20.8% and control 21.3%); with infection most commonly reported (VCS 10.1% and control 11.2%). Overall mortality in the trial was low, with one death in the voclosporin arm and five in the control arm. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids, or glucose.Conclusion:The AURORA study met its primary endpoint and VCS was efficacious in Hispanic/Latino ethnicity patients, a difficult to treat group.Disclosure of Interests:Cristina Arriens Grant/research support from: - BMS: Investigator Initiated Trial Research Funding, GSK: Investigator Initiated Trial Research Funding, Exagen: Research Grant, Consultant of: AstraZeneca (Sci Ad Board Dec 2017), GSK (Sci Ad Board Oct 2018), BMS (Sci Ad Board April 2019), Svetlana Polyakova: None declared, Igor Adzerikho: None declared, Simrat Randhawa Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals, Inc., Neil Solomons Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals.

A phase III study (APROMISS) of AL3818 (Catequentinib, Anlotinib) hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11505-11505
Author(s):  
Brian Andrew Van Tine ◽  
Sant P. Chawla ◽  
Jonathan C. Trent ◽  
Breelyn A. Wilky ◽  
Rashmi Chugh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Synovial Sarcoma ◽  
Primary Endpoint ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Phase 3 ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Trial Information

11505 Background: AL3818 (Catequentinib, Anlotinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. The primary objective of this Phase 3 study is to evaluate the efficacy of AL3818 monotherapy in patients (pts) with synovial sarcoma (SS) comparing with dacarbazine in randomization setting. Methods: Patients with a diagnosis of synovial sarcoma requiring second line or further line treatment were eligible for enrollment. The regimen was a 21-day cycle with oral AL3818 administered on 14 days on and 7 days off. This phase 3 trial is randomized in 2:1 ratio of AL3818 comparing to dacarbazine with option of crossover after PD of dacarbazine treatment. Progression free survival (PFS) with Log Rank test is the primary endpoint and this trial for SS is currently completed enrolled in US and Italy. Results: Total 79 pts initiated treatment and are evaluable, 52 received AL3818 as treatment arm (T), and 27 received dacarbazine (D) as control arm (C). Arms T/C median ages were 40.5/42.0 years (range: 18-70+) and 20/16 (38.5%/59.3%) were male. Overall, PFS was 2.89 months (95% CI: 2.73 – 6.87) for AL3818 and 1.64 (95% CI: 1.45 – 2.70) for D. The PFS of study met the primary endpoint with a p-value of 0.0015 and a HR of 0.449 (95% CI: 0.270– 0.744). At the month 4, 6, and 12, the percentages of progression free patients for AL3818 were 48.1%, 42.3% and 26.9%; and for D were 14.85%, 11.1% and 3.7%. For grade 3 treatment-related adverse events, 12(23.1%) of pts experienced for AL3818 and 7(25.9%) of pts experienced for D. The most common AL3818 related grade 3 AEs were diarrhea (5.8%) and hypertension (3.8%). Conclusions: This phase III trial demonstrates improved disease control and superior progression free survival for AL3818 vs dacarbazine in advanced SS. In addition, the study further confirms the acceptable benefit-risk profile of AL3818 from the prior randomized Phase 2b soft tissue sarcoma study (NCT02449343). AL3818 is a meaningful treatment option for pts with advanced SS. Clinical trial information: NCT 03016819 Clinical trial information: NCT03016819.

CA184-095: A randomized, double-blind, phase III trial to compare the efficacy of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients (pts) with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4691-TPS4691 ◽  
Author(s):  
Tomasz M. Beer ◽  
Christopher Logothetis ◽  
Padmanee Sharma ◽  
Alberto Bossi ◽  
Brent McHenry ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Phase 1 ◽  
Human Monoclonal Antibody ◽  
Specific Antigen ◽  
Specific Treatment ◽  
Phase Iii ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
To Receive

TPS4691 Background: Ipilimumab (Ipi), a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi has demonstrated overall survival (OS) benefit in two Phase 3 trials for advanced melanoma, with side effects that were managed using product-specific treatment guidelines. In addition, in Phase 1/2 trials in metastatic CRPC, Ipi has shown clinical activity (as measured by prostate-specific antigen [PSA] declines and RECIST response) with no unexpected toxicities. While docetaxel is standard therapy for metastatic CRPC, its use may be delayed until pts develop symptoms. As such, this global (~150 sites in 25 countries) Phase 3 study (ClinicalTrials.gov identifier: NCT01057810) is evaluating Ipi vs placebo in chemotherapy-naïve pts with asymptomatic or minimally symptomatic CRPC without visceral metastases. Methods: The primary endpoint is OS; secondary endpoints include progression-free survival, time to pain progression, and time to non-hormonal systemic therapy. The study is designed to detect a 9.3 month difference (HR=0.7) in OS with 90% power and 0.05 two-sided significance. Pts are randomized at a 2:1 ratio to receive Ipi 10 mg/kg every 3 weeks for up to 4 doses or placebo, respectively, as induction therapy. Eligible pts will continue to receive maintenance therapy of blinded study drug every 12 weeks until treatment stopping criteria are met, withdrawal of consent, or study closure. The accrual goal is 600 pts randomized. [Table: see text] [Table: see text]

Pembrolizumab (pembro) for recurrent head and neck squamous cell carcinoma (HNSCC): Post hoc analyses of phase 3 KEYNOTE-040 prior radiation treatment (RT) and disease state.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6026-6026
Author(s):  
Kevin J. Harrington ◽  
Ezra E.W. Cohen ◽  
Denis Soulieres ◽  
José Dinis ◽  
Lisa F. Licitra ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Radiation Treatment ◽  
Standard Of Care ◽  
Disease State ◽  
Prolonged Survival ◽  
Open Label ◽  
Phase 3 ◽  
Post Hoc ◽  
To Receive ◽  
Clinical Trial Information

6026 Background: The open-label, randomized, phase 3 KEYNOTE-040 study (NCT02252042) showed that pembro vs standard of care (SOC) chemotherapy prolonged survival in patients (pts) with recurrent and/or metastatic HNSCC whose disease progressed during/after platinum-based therapy. Post hoc analyses were conducted to evaluate pembro vs SOC by prior RT and disease state (metastatic, locoregionally recurrent [referred to as recurrent herein], or recurrent and metastatic [R/M]). Methods: Pts (N = 495) were randomly assigned (1:1) to receive pembro (200 mg Q3W) or investigator choice of methotrexate (40 mg/m2 QW), docetaxel (75 mg/m2 Q3W), or cetuximab (400 mg/m2 loading dose, then 250 mg/m2 QW). Primary end point was OS; PFS and ORR were secondary end points. Results: 175, 97, and 195 pts had metastatic, recurrent, and R/M disease, respectively (28 pts had unknown disease state); 64 pts had no prior RT; 431 pts had prior RT. As in the ITT population, prolonged survival benefit and trend toward improved PFS and ORR was observed with pembro vs SOC in pts with prior RT (Table), and prolonged survival benefit was observed with pembro vs SOC in pts with metastatic and R/M, but not recurrent, disease. Conclusions: In this post hoc analysis, patients with prior RT benefited from treatment with pembro vs SOC. For patients without RT, sample sizes are too small to draw any definitive conclusions. Survival benefit of pembro vs SOC was observed in pts with metastatic and R/M disease. Clinical trial information: NCT02252042. [Table: see text]

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