scholarly journals FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements

2020 ◽  
Vol 16 (30) ◽  
pp. 2385-2399 ◽  
Author(s):  
Tanios S Bekaii-Saab ◽  
Juan W Valle ◽  
Eric Van Cutsem ◽  
Lorenza Rimassa ◽  
Junji Furuse ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Survival Duration ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Duration Of Response

FGFR2 rearrangements resulting in dysregulated signaling are drivers of cholangiocarcinoma (CCA) tumorigenesis, and occur almost exclusively in intrahepatic CCA. Pemigatinib, a selective, potent, oral inhibitor of FGFR1–3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring FGFR2 fusions/rearrangements. We describe the study design of FIGHT-302, an open-label, randomized, active-controlled, multicenter, global, Phase III study comparing the efficacy and safety of first-line pemigatinib versus gemcitabine plus cisplatin in patients with advanced CCA with FGFR2 rearrangements (NCT03656536). The primary end point is progression-free survival; secondary end points are objective response rate, overall survival, duration of response, disease control rate, safety and quality of life. Clinical Trial Registration: NCT03656536 ( ClinicalTrials.gov )

FIGHT-302: Phase III study of first-line (1L) pemigatinib (PEM) versus gemcitabine (GEM) plus cisplatin (CIS) for cholangiocarcinoma (CCA) with FGFR2 fusions or rearrangements.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS592-TPS592 ◽  
Author(s):  
Tanios S. Bekaii-Saab ◽  
Juan W. Valle ◽  
Eric Van Cutsem ◽  
Lorenza Rimassa ◽  
Junji Furuse ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Phase Iii ◽  
Phosphate Binders ◽  
Survival Duration ◽  
Open Label ◽  
History Of

TPS592 Background: For advanced CCA, standard of care 1L systemic treatment is GEM + CIS. Genetic alterations in intrahepatic CCA provide potential therapeutic targets. Fibroblast growth factor receptor (FGFR) 2 gene rearrangements driving CCA tumorigenesis were identified almost exclusively in intrahepatic CCA patients (pts) (incidence, 10–16%). In phase 2, PEM (INCB054828), a selective, potent, oral FGFR1–3 inhibitor elicited an objective response rate (ORR) of 35.5% and median progression-free survival (PFS) of 6.9 months (mo) in previously treated, locally advanced or metastatic CCA with FGFR2 rearrangements (NCT02924376). FIGHT-302, a randomized, open-label, phase 3 study will evaluate efficacy and safety of 1L PEM vs GEM + CIS in unresectable/metastatic CCA with FGFR2 fusions or rearrangements (NCT03656536). Methods: Eligible pts are adults with confirmed unresectable/metastatic CCA; no prior systemic therapy for advanced disease < 6 mo before enrollment; radiographically measurable/evaluable disease (per RECIST v1.1); ECOG PS ≤1; documented FGFR2 fusions or rearrangements. Exclusions include clinically significant corneal or retinal disorder; history of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic soft tissue calcification; untreated CNS metastases or history of uncontrolled seizures. Pts will be randomized (1:1; stratified by region and tumor burden) to PEM 13.5 mg QD on a 21-day (d) cycle or GEM (1000 mg/m2) + CIS (25 mg/m2) on D1 and D8 of 21-d cycles (max 8). Crossover to PEM allowed after confirmed progression. PEM titration to 18 mg from cycle 2 allowed for pts without hyperphosphatemia (serum phosphate > 5.5 mg/dL) and Grade ≥2 treatment-related adverse events during cycle 1. Hyperphosphatemia will be managed with diet modifications, phosphate binders, diuretics, or dose adjustments. Treatment will continue until progression or unacceptable toxicity. Primary endpoint is PFS (by independent review). Secondary endpoints are ORR, overall survival, duration of response, disease control rate, safety, and quality of life. Four pts (target N = 432) are enrolled as of Sep 25, 2019. Clinical trial information: NCT03656536.

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.

ELOQUENT-2: A phase III, randomized, open-label trial of lenalidomide/dexamethasone (Len/Dex) with or without elotuzumab (Elo) in relapsed or refractory multiple myeloma (RR MM) (CA204-004).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8112-TPS8112
Author(s):  
Sagar Lonial ◽  
Paul Gerard Guy Richardson ◽  
Philippe Moreau ◽  
Robert Z. Orlowski ◽  
Jesùs F. San-Miguel ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Surface Glycoprotein ◽  
Phase Iii ◽  
Open Label ◽  
Cell Surface Glycoprotein ◽  
Open Label Phase ◽  
Related Quality ◽  
Duration Of Response

TPS8112 Background: MM remains incurable and patients (pts) typically relapse or become refractory to current treatments. Novel regimens are needed to improve pt outcomes. Elo is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. Len/Dex is approved for treatment of relapsed MM and an objective response rate (ORR) of ~60% was reported in phase III trials of this combination in RR MM. In a phase II study (N=73) of Elo (10 or 20 mg/kg) in combination with Len/Dex in pts with RR MM, the 10 mg/kg group (n=36) demonstrated an ORR of 92% and median progression-free survival (PFS) that was not reached after a median follow-up of 14.1 months. Encouraging activity was seen in patients with high-risk cytogenetics and/or stage 2-3 disease. Based on these data, a randomized, open-label phase III trial has been initiated to determine if the addition of Elo to Len/Dex will improve PFS in patients with RR MM compared with Len/Dex alone. Methods: Pts (N=640) with RR MM and 1-3 prior therapies are eligible, including pts with mild or moderate renal impairment. Pts are randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days 1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 in subsequent cycles. Dex 8 mg IV + 28 mg PO is used during the weeks with Elo. Treatment will continue until disease progression, death, or withdrawal of consent. Patients will be followed for tumor response every 4 weeks until progressive disease and then survival every 12 weeks. The primary endpoint is PFS (90% power for a hazard ratio [experimental to control arm] of 0.74) and the secondary endpoints are ORR and overall survival. Exploratory endpoints are safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, and pharmacokinetics and immunogenicity of Elo. Potential biomarkers will also be assessed. As of January 10th, 2012, 107 pts were enrolled and 68 pts were treated. NCT01239797.

Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
Noah M. Hahn ◽  
Thomas Powles ◽  
Christophe Massard ◽  
Hendrik-Tobias Arkenau ◽  
Terence W. Friedlander ◽  
...  
Keyword(s):  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Kidney Injury ◽  
Progression Free Survival ◽  
Anticancer Therapy ◽  
Clinical Activity ◽  
Open Label ◽  
Duration Of Response ◽  
Grade 3

4525 Background: Anti-PD-L1 immunotherapy shows promising clinical activity in UC. We report a planned update of the safety and efficacy of durvalumab in patients (pts) with locally advanced/metastatic UC from a multicenter, phase 1/2 open-label study. Methods: Pts received durvalumab 10 mg/kg every 2 weeks (Q2W) up to 12 months (mo) or until unacceptable toxicity, progression, or starting another anticancer therapy. Primary endpoints were safety and confirmed objective response rate (ORR) by blinded independent central review (RECIST v1.1). Duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Tumor PD-L1 expression was assessed by Ventana SP263 assay (PD-L1 high = ≥25% PD-L1 expression on tumor or immune cells). Results: As of Oct 24, 2016 (data cutoff [DCO]), 191 pts had received treatment. Median follow-up was 5.78 mo (range, 0.4–25.9). All pts had Stage 4 disease and 99.5% had prior anticancer therapy (95.3% post-platinum). As of DCO, ORR was 17.8% (34/191), including 7 CRs, with responses observed regardless of PD-L1 status (Table). Responses occurred early (median time to response, 1.41 mo) and were durable (median DoR not reached [NR]). Median PFS and OS were 1.5 mo (95% CI, 1.4, 1.9) and 18.2 mo (95% CI, 8.1, not estimable [NE]), respectively; the 1-year OS rate was 55.0% (95% CI, 43.9%, 64.7%). Grade 3/4 treatment-related AEs occurred in 6.8% of pts; grade 3/4 immune-mediated (im)AEs occurred in 4 pts; 2 pts discontinued due to imAEs (acute kidney injury and autoimmune hepatitis). Conclusions: Durvalumab 10 mg/kg Q2W shows favorable clinical activity and an excellent safety profile in locally advanced/metastatic UC pts. Table. Antitumor activity in UC pts, including second-line or greater (≥2L) post-platinum pts Clinical trial information: NCT01693562. [Table: see text]

Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer

2009 ◽  
Vol 27 (33) ◽  
pp. 5513-5518 ◽  
Author(s):  
David Cunningham ◽  
Ian Chau ◽  
Deborah D. Stocken ◽  
Juan W. Valle ◽  
David Smith ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Primary Outcome Measure ◽  
Phase Iii ◽  
Open Label

PurposeBoth gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).Patients and MethodsPatients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.ResultsBetween May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.ConclusionOn the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.

scholarly journals Olaparib with or without bevacizumab or bevacizumab and 5-fluorouracil in advanced colorectal cancer: Phase III LYNK-003

2021 ◽  
Author(s):  
Tae Won Kim ◽  
Julien Taieb ◽  
Ellen B Gurary ◽  
Nati Lerman ◽  
Karen Cui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Standard Of Care ◽  
Phase Iii ◽  
Clinical Trial Registration ◽  
Duration Of Response ◽  
Reduced Toxicity

Oxaliplatin-based chemotherapy with a regimen such as FOLFOX with or without targeted therapy is a standard of care option for advanced colorectal cancer; however, long-term exposure to oxaliplatin is associated with cumulative toxicity. Growing evidence suggests maintenance therapy with a less intensive regimen after platinum-based induction therapy can provide continuing benefit with reduced toxicity. We describe the rationale and design of the Phase III LYNK-003 trial, which will evaluate the efficacy and safety of olaparib with or without bevacizumab compared with 5-fluoruracil plus bevacizumab in patients with unresectable or metastatic colorectal cancer that has not progressed on an induction course of FOLFOX plus bevacizumab. The primary end point is progression-free survival by independent central review; secondary end points include overall survival, objective response, duration of response and safety. Clinical trial registration: NCT04456699

AcceleRET Lung: A phase III study of first-line pralsetinib in patients (pts) with RET-fusion+ advanced/metastatic non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS9633-TPS9633 ◽  
Author(s):  
Benjamin Besse ◽  
Enriqueta Felip ◽  
Corinne Clifford ◽  
Melinda Louie-Gao ◽  
Jennifer Green ◽  
...  
Keyword(s):  
Phase 1 ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Survival Duration ◽  
First Line ◽  
Open Label ◽  
Eligibility Criteria ◽  
Multiple Tumor ◽  
Platinum Based Chemotherapy

TPS9633 Background: RET gene fusions have been identified as oncogenic drivers in multiple tumor types, including 1-2% of NSCLC, but no selective RET inhibitors are approved for use. The investigational RET inhibitor, pralsetinib, potently and selectively targets oncogenic RET alterations, including those that confer resistance to multikinase inhibitors. In the registration-enabling phase 1/2 study (ARROW; NCT03037385), pts with RET-fusion+ NSCLC treated with 400 mg once daily (QD) of pralsetinib (N = 80) after platinum-based chemotherapy achieved an overall response rate (ORR) of 61% (95% CI 50, 72; 2 responses pending confirmation) per independent central review. In addition, a promising ORR of 73% (all centrally confirmed responses) was attained in the treatment naïve cohort (N = 26). Most treatment-related adverse events were grade 1-2 across the entire safety population treated at 400 mg QD (N = 354). AcceleRET Lung, an international, open-label, randomized, phase 3 study, will evaluate the efficacy and safety of pralsetinib versus standard of care (SOC) for first-line treatment of advanced/metastatic RET fusion+ NSCLC (NCT04222972). Methods: Approximately 250 pts with metastatic RET-fusion+ NSCLC will be randomized 1:1 to oral pralsetinib (400 mg QD) or SOC (non-squamous histology: platinum/pemetrexed ± pembrolizumab followed by maintenance pemetrexed ± pembrolizumab; squamous histology: platinum/gemcitabine). Stratification factors include intended use of pembrolizumab, history of brain metastases, and ECOG PS. Key eligibility criteria include no prior systemic treatment for metastatic disease; RET-fusion+ tumor by local or central assessment; no additional actionable oncogenic drivers; no prior selective RET inhibitor; measurable disease per RECIST v1.1. Pts randomized to SOC will be permitted to cross-over to receive pralsetinib upon disease progression. The primary endpoint is progression-free survival (blinded independent central review; RECIST v1.1). Secondary endpoints include ORR, overall survival, duration of response, disease control rate, clinical benefit rate, time to intracranial progression, intracranial ORR, safety/tolerability and quality of life evaluations. Recruitment has begun with sites (active or planned) in North America, Europe and Asia. Clinical trial information: NCT04222972 .

NRG-GI004/SWOG-S1610: Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study—A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS158-TPS158
Author(s):  
Michael J. Overman ◽  
Greg Yothers ◽  
Samuel A. Jacobs ◽  
Hanna Kelly Sanoff ◽  
Deirdre Jill Cohen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Dna Mismatch ◽  
Best Response ◽  
Related Quality ◽  
Duration Of Response ◽  
Pathway Inhibition

TPS158 Background: Despite activity of programmed cell death-1 (PD-1) pathway inhibition in dMMR/MSI-H mCRC, approximately one-third of patients demonstrate progressive disease as best response to anti-PD1 monotherapy. Preclinical models have demonstrated synergistic interactions between FOLFOX, anti-VEGF, and anti-PD-1. We hypothesize that the dMMR/MSI-H mCRC subset may be more effectively targeted by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-1 therapy (atezo) alone. Methods: Initially a three-arm study, the mFOLFOX6/bev arm was closed to new enrollment on 6-4-20 due to emerging data; the redesigned COMMIT is a prospective phase III open-label trial that will randomize (1:1) mCRC dMMR/MSI-H pts (N=211) to either atezo monotherapy or mFOLFOX6/bev+atezo combination. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is progression-free survival (PFS) as assessed by site investigator. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and centrally-reviewed PFS. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Support: U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.

Pemigatinib for previously treated locally advanced/metastatic cholangiocarcinoma (CCA): Update of FIGHT-202.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4086-4086
Author(s):  
Ghassan K. Abou-Alfa ◽  
Vaibhav Sahai ◽  
Antoine Hollebecque ◽  
Gina M. Vaccaro ◽  
Davide Melisi ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Safety Data ◽  
Progression Free Survival ◽  
Complete Response ◽  
Treatment Interruption ◽  
Primary Data ◽  
Efficacy And Safety ◽  
Prior Therapy ◽  
Duration Of Response

4086 Background: Pemigatinib (PEMI), a potent, selective, oral FGFR1-3 inhibitor, has shown efficacy and safety in patients (pts) with CCA and FGFR2 rearrangements/fusions in FIGHT-202 (NCT02924376; objective response rate [ORR], 35.5%; duration of response [DOR], 7.2 months [mo]). Overall survival (OS: 21.1 mo) was not mature in the primary report (Abou-Alfa. Lancet Oncol 2020; cutoff: Mar 22, 2019); herein we report matured efficacy and safety data from FIGHT-202 (cutoff: Apr 7, 2020). Methods: Pts (≥18 y) with known FGF/FGFR alterations and progression after ≥1 prior therapy had FGFR2 rearrangements/fusions (cohort A), other FGF/FGFR alterations (B), or no FGF/FGFR alterations (C). Pts received PEMI 13.5 mg QD (21-d cycle; 2 wks on, 1 wk off) until progression or toxicity. Primary endpoint: independent, centrally confirmed ORR (cohort A); secondary endpoints: ORR (cohorts B, C; cohorts A and B combined); DOR, disease control rate (DCR), progression free survival (PFS), OS, and safety. A post-hoc analysis in cohort A evaluated mOS in responders (pts with complete response [CR] or partial response [PR]) vs non-responders (pts with progressive disease [PD] or stable disease (SD]). Results: At cutoff, 147 pts were enrolled (cohort A, n=108; B, n=20; C, n=17; FGF/FGFR status undetermined, n=2); median follow-up was 30.4 (range, 4.9–38.7) mo and median treatment duration was 5.9 (0.2–36.5) mo. In cohort A, 9.3% of pts remained on therapy at cutoff; in cohorts B and C, all pts had discontinued. Pts discontinued mainly for PD (67.6%, 75%, and 64.7% in cohorts A, B, and C respectively). Independent, centrally confirmed ORR was 37.0%; mOS was 17.5 mo (95% CI, 14.4-22.9) in cohort A (Table 1). mOS for responders (n=40) vs non-responders (n=68) was 30.1 (95% CI, 21.5-NE) mo vs 13.7 (9.6-16.1) mo. Overall, most common all-cause treatment-emergent adverse events (TEAEs) were hyperphosphatemia (58.5%; grade ≥3, 0%), alopecia (49.7%; 0%), diarrhea (46.9%; 3.4%), fatigue (43.5%; 5.4%), nausea (41.5%; 2%), and dysgeusia (40.8%; 0%); 10.2%, 13.6% and 42.2% of pts discontinued, had dose reduction, and treatment interruption due to TEAEs, respectively. Conclusions: These results reinforce the primary data, showing continued, durable responses and sustained tolerability in pts receiving PEMI for CCA harboring FGFR2 rearrangements/fusions. Notably, the matured OS is longer than historical data; OS for responders was more than twice as long vs for non-responders. Clinical trial information: NCT02924376. [Table: see text]

A phase II multicenter study of aflibercept (AFL) in combination with cisplatin (C) and pemetrexed (P) in patients with previously untreated advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7541-7541 ◽  
Author(s):  
Hongbin Chen ◽  
Manuel R. Modiano ◽  
Joel W. Neal ◽  
Julie R. Brahmer ◽  
James R. Rigas ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Meta Analysis ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Uncontrolled Hypertension ◽  
First Line ◽  
Open Label

7541 Background: AFL is a recombinant human fusion protein that acts as a decoy receptor and prevents the interaction of vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor with their receptors. This study evaluated the efficacy and safety of AFL in combination with first-line chemotherapy of C and P in NSCLC. Methods: This phase II, single arm, open label, multicenter trial in patients with previously untreated, locally advanced, or metastatic NSCLC excluded patients with squamous histology, cavitating lesions, ECOG > 1, uncontrolled hypertension, or brain/CNS metastases. All patients received IV AFL 6 mg/kg, P 500 mg/m2, and C 75mg/m2, every 3 weeks for up to 6 cycles. For those who completed the combined chemotherapy, Q3W administration of AFL was to continue until disease progression, intolerable toxicity, or any other cause for withdrawal. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). Planned sample size was 72 patients. Results: The study was closed prematurely due to 3 confirmed cases of reversible posterior leukoencephalopathy syndrome (RPLS). A total of 42 patients were enrolled. Median age was 61.5 years; 54.8% were male, 85.7% white and 50% ECOG 0. A median of 4 cycles of AFL was administered. The most common treatment-emergent adverse events (TEAEs) of any grade were nausea (69%) and fatigue (67%), with hypertension (36%) as the most common grade 3/4 TEAE. The 3 patients with RPLS were Caucasian women. Two had a history of hypertension and both experienced elevated BP and reduced CrCl. Of the 38 patients evaluable for response, ORR was 26.3% (95% CI, 12.3-40.3%) and median PFS was 5 months (95% CI, 4.3-7.1). Conclusions: The rate of RPLS observed in this study with AFL + C + P was higher than anticipated. A meta-analysis of safety from three large placebo-controlled studies reported no RPLS among 1333 patient treated with AFL + chemotherapy, and none was reported in prior combination studies of AFL + P or AFL + C + docetaxel. Though the study was stopped early, ORR and PFS were in accordance with most historical first-line NSCLC studies.

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