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.

ELOQUENT-1: A phase III, randomized, open-label trial of lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma (CA204-006).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8113-TPS8113 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Thierry Facon ◽  
Paul Gerard Guy Richardson ◽  
Robert Z. Orlowski ◽  
Jesùs F. San-Miguel ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Surface Glycoprotein ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Open Label ◽  
Cell Surface Glycoprotein ◽  
Prior Therapy

TPS8113 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. In a MM xenograft mouse model, the combination of Elo + lenalidomide (Len) significantly reduced tumor volume in a synergistic manner compared with either agent alone. In a phase 2 study (N=73) of Elo (10 or 20 mg/kg) in combination with Len and low-dose-dexamethasone (Dex) in pts with RR MM, the 10 mg/kg dose group (n=36) demonstrated objective response rates (ORR) of 92% in all pts, and 100% in pts who had received only 1 prior therapy (n=16). The higher response rate in pts with fewer prior lines of therapy provides a rationale for investigating this combination earlier in the disease course. This randomized, open-label, phase 3 trial will determine if the addition of Elo to Len/Dex improves progression-free survival (PFS) in pts with newly diagnosed, untreated MM. Methods: Pts (N=750) with newly diagnosed symptomatic MM ineligible for stem cell transplant will be randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days1-21) 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 of cycles 3-18 followed by 20 mg/kg on day 1 of cycle 19 onward. 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. Pts will be followed up for response every 4 weeks until progressive disease and for survival every 16 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 1, 2012, 13 pts were enrolled and 9 pts were treated. NCT01335399.

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.

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.

FIDES-01, a phase II study of derazantinib in patients with unresectable intrahepatic cholangiocarcinoma (iCCA) and FGFR2 fusions and mutations or amplifications (M/A).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS597-TPS597
Author(s):  
Milind M. Javle ◽  
Walid Labib Shaib ◽  
Stephan Braun ◽  
Marc Engelhardt ◽  
Mitesh J. Borad ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Current Status ◽  
Open Label ◽  
Open Label Phase ◽  
Duration Of Response ◽  
Symptom Response

TPS597 Background: Deregulation of the FGFR signaling pathway is implicated in various cancers. In iCCA, FGFR genetic aberrations include FGFR2 fusions and, less commonly, FGFR2 M/A. iCCA prognosis is poor, and chemotherapeutic and targeted treatment options are limited. While FGFR2 fusions are acknowledged oncogenic drivers, the oncogenic potential of FGFR2 M/A is less well defined. Derazantinib (DZB) is an investigational, oral small-molecule kinase inhibitor with activity against FGFR1, 2 and 3, which demonstrated antitumor activity in patients with unresectable iCCA with FGFR2 fusions. Based on preliminary efficacy data demonstrating durable responses of > 6 months and a clinically meaningful progression-free survival in a subset of iCCA patients harboring FGFR2 M/A (NCT01752920), the multicenter, multicohort open-label phase 2 study FIDES-01 is evaluating the effect of DZB in separate cohorts of iCCA patients with FGFR2 fusions or FGFR2 M/A. Methods: The new cohort evaluates 300 mg once daily dosing of DZB in patients with unresectable iCCA with FGFR2 M/A per liquid or tissue biopsy-based next generation sequencing and at least one previous systemic therapy. Treatment will continue until progressive disease, intolerance, withdrawal of informed consent, or death. Using a Simon’s two-stage design, the primary endpoint to assess the antitumor activity of DZB is the proportion of patients with PFS at 3 months (PFS3; per RECIST 1.1 central review). Secondary objectives are evaluation of median PFS, objective response rate, duration of response, safety profile, quality of life (incl., QLQ-C30, QLQ-BIL21, EQ-5D), and symptom response from baseline. Current status: The study was initiated in July 2019 with planned enrollment of 43 patients with confirmed FGFR2 M/A. Clinical trial information: NCT03230318.

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

Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): A multicenter, randomized, phase III study (PERSEUS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8055-TPS8055 ◽  
Author(s):  
Pieter Sonneveld ◽  
Annemiek Broijl ◽  
Francesca Gay ◽  
Mario Boccadoro ◽  
Hermann Einsele ◽  
...  
Keyword(s):  
Stem Cell ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3 ◽  
Related Quality ◽  
Duration Of Response ◽  
Line Of Therapy

TPS8055 Background: DARA, a human, CD38-targeting, IgGκ monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory MM (RRMM), and in combination with standard-of-care regimens in RRMM and transplant-ineligible NDMM. Given the initial safety and efficacy observed with DARA plus VRd (D-VRd) in the safety run-in cohort of the ongoing phase 2 GRIFFIN study in TE NDMM pts, the phase 3 PERSEUS study will evaluate the efficacy and safety of D-VRd versus VRd alone in TE NDMM. Methods: This is an ongoing multicenter, open-label, randomized phase 3 study of D-VRd versus VRd alone in TE NDMM pts. Approximately 690 pts across Europe will be stratified by ISS stage and cytogenetic risk (high risk defined as presence of del17p, t[4;14], or t[14;16]) and randomized in a 1:1 ratio. All pts will receive VRd (V: 1.3 mg/m2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-21; d: 40 mg PO Days 1-4, 9-12) for 4 pre-transplant induction and 2 post-transplant consolidation cycles (all 28-d cycles), followed by R (10 mg PO Days 1-28) maintenance until progressive disease (PD). Pts in the DARA group will also receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W in maintenance Cycles 7+ until PD. After induction, pts will undergo melphalan 200 mg/m2 conditioning and autologous stem cell transplantation (ASCT). Pts in the DARA group who achieve sustained minimal residual disease (MRD) negativity (10–5 threshold; assessed by NGS) for 12 months after ≥24 months of maintenance will stop DARA but continue R maintenance until PD; upon loss of CR or MRD-negative status, pts will restart DARA treatment. All pts will receive preinfusion medications. The primary endpoint is progression-free survival (PFS). Secondary endpoints include MRD-negative rate, overall response rate, PFS on next line of therapy, overall survival, time to and duration of response, health-related quality of life, pharmacokinetics, immunogenicity, stem cell yield after mobilization, time to engraftment post-ASCT, and safety. Clinical trial information: NCT03710603.

Pembrolizumab vs paclitaxel as second-line treatment for Asian patients with PD-L1–positive advanced gastric or gastroesophageal cancer (GC) in the phase III KEYNOTE-063 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16586-e16586 ◽  
Author(s):  
Hyun Cheol Chung ◽  
Yoon-Koo Kang ◽  
Zhendong Chen ◽  
Yuxian Bai ◽  
Wan Zamaniah Wan Ishak ◽  
...  
Keyword(s):  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Sample ◽  
Phase Iii ◽  
Second Line ◽  
Open Label ◽  
Asian Patients ◽  
Significance Threshold ◽  
Open Label Phase

e16586 Background: Approximately 75% of GC cases occur in Asian persons. Pembrolizumab has shown antitumor activity in global studies of GC. KEYNOTE-063 (NCT03019588) is a randomized, open-label, phase 3 trial in Asian patients with advanced PD-L1–positive (combined positive score [CPS] ≥1) GC that progressed after platinum + fluoropyrimidine chemotherapy. After the KEYNOTE-063 study began, results of the global KEYNOTE-061 study (NCT02370498) showed that pembrolizumab did not prolong overall survival (OS) vs paclitaxel in patients previously treated for advanced GC (median OS, 9.1 months vs 8.3 months; hazard ratio [HR], 0.82; 95% CI, 0.66-1.03; 1-sided P= 0.0421 [significance threshold for OS was 1-sided P= 0.0135]). Methods: Eligible patients were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg Q3W for up to 35 cycles (~2 years) or standard-dose paclitaxel. The primary efficacy end points were OS and progression-free survival (PFS). Planned enrollment was ~360 patients. Results: Because pembrolizumab did not significantly prolong OS in KEYNOTE-061, enrollment in KEYNOTE-063 was discontinued after 94 patients were enrolled (47 patients in each treatment group). In these Asian patients, median OS was 8.4 months in the pembrolizumab group and 7.7 months in the paclitaxel group; median PFS was 1.9 months and 4.0 months, respectively (Table). Objective response rate (ORR) and median duration of response (DOR) are shown in the Table. Drug-related adverse events (AEs) occurred in 59.6% of patients receiving pembrolizumab and in 95.5% of patients receiving paclitaxel (Table). Conclusions: In this small sample of Asian patients with PD-L1–positive advanced GC, definitive conclusions are limited; however, second-line pembrolizumab monotherapy seems to be well tolerated in this patient population. Because this study was terminated early, there was insufficient power for comparisons between groups; therefore, these data should be viewed with caution. Clinical trial information: NCT03019588 . [Table: see text]

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 )

IMbrave150: Updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 267-267
Author(s):  
Richard S. Finn ◽  
Shukui Qin ◽  
Masafumi Ikeda ◽  
Peter R. Galle ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Treatment Benefit ◽  
Recist 1.1 ◽  
Open Label Phase ◽  
Phase Iii Study

267 Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 mo follow-up, both coprimary endpoints were met, with statistically significant and clinically meaningful improvements observed with atezo + bev vs sor for OS (HR, 0.58 [95% CI, 0.42, 0.79]; P<0.001) and independently-assessed progression-free survival (PFS; per RECIST 1.1; HR, 0.59 [95% CI, 0.47, 0.76]; P<0.001) (Finn, et al. N Engl J Med 2020). Here, we report an updated OS analysis for IMbrave150. Methods: The global, multicenter, randomized, open-label, Phase III study IMbrave150 enrolled 501 systemic treatment–naive pts with unresectable HCC, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts were randomized 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator. This post hoc, descriptive OS analysis was conducted with 12 mo of additional follow up from the primary analysis. Results: 501 pts were enrolled, including 336 to atezo + bev and 165 to sor. At the clinical cut-off date of Aug 31, 2020, median follow-up was 15.6 mo and 280 OS events were observed. Median OS was 19.2 mo with atezo + bev vs 13.4 mo with sor (HR, 0.66 [95% CI, 0.52, 0.85]; P=0.0009). Survival at 18 mo was 52% with atezo + bev and 40% with sor. Survival benefit with atezo + bev over sor was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo + bev was in line with the primary analysis, with more pts achieving complete response (CR; 7.7%) than previously reported. Additional response data are in Table. Safety was aligned with the primary analysis, with no new signals identified. Conclusions: IMbrave150 showed consistent clinically meaningful treatment benefit and safety with 12 mo of additional follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC. Clinical trial information: NCT03434379. [Table: see text]

Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs letrozole alone for frontline treatment of ER+/HER2– advanced breast cancer (PALOMA-1; TRIO-18).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
Richard S. Finn ◽  
John Crown ◽  
Istvan Lang ◽  
Katalin Boer ◽  
Igor Bondarenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Survival Data ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Frontline Treatment ◽  
Open Label Phase

1001 Background: Preclinical data identified a synergistic role for P and hormone blockade in blocking growth of ER+ breast cancer (BC) cell lines. PALOMA-1 was an open-label phase II trial comparing progression-free survival (PFS) in patients (pts) with advanced ER+/HER2– BC treated with P+L or L alone. Median PFS increased with addition of P to L to 20.2 mos (vs 10.2 mos with L alone; HR = 0.488), with an acceptable safety profile, leading to accelerated approval by the US FDA. These results were confirmed in the phase 3 PALOMA-2 trial. At the time of the final PFS analysis, overall survival (OS) data were immature with only 61 events in both arms and a median follow-up of < 30 mos with a trend in favor of P+L vs L (37.5 vs 33.3 mos; HR = 0.813; P= 0.211). Here we present final OS results. Methods: PALOMA-1 was a 2-part study evaluating P+L in ER+/HER2– advanced BC. Part 1 enrolled postmenopausal pts with this subtype using only ER+/HER2– while Part 2 enrolled pts of this subtype additionally screened for CCND1 amplification and/or loss of p16. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate, OS, safety, and correlative biomarker studies. A total of 165 pts were randomized; 66 in Part 1 and 99 in Part 2. Baseline characteristics were balanced between treatment arms. In both parts, pts were randomized 1:1 to receive P+L or L alone. OS data were collected as well as post-study therapy. Results: As of Dec 2016, there were 116 OS events. Median OS was 37.5 mos (95% CI: 31.4, 47.8) with P+L vs 34.5 mos (95% CI: 27.4, 42.6) for L (HR = 0.897 [95% CI: 0.623, 1.294]; P= 0.281). Median OS was 37.5 vs 33.3 mos (HR = 0.837; P= 0.280) for Part 1 and 35.1 vs 35.7 mos (HR = 0.935; P= 0.388) for Part 2. 78.6% of pts in the P+L arm received post-study systemic therapy vs 86.4% in the L arm. More pts in the L arm received ≥3 lines of therapy (37% vs 18%). Further subgroup analyses and details on post-study therapies will be presented. Conclusions: In PALOMA-1, P+L provided a statistically non-significant trend towards an improvement in OS. Survival data from the phase III, PALOMA-2 study is awaited. Sponsor: Pfizer; Clinical trial information: NCT00721409.

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