LUX-breast 2: Phase II, open-label study of oral afatinib in HER2-overexpressing metastatic breast cancer (MBC) patients (pts) who progressed on prior trastuzumab (T) and/or lapatanib (L).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS651-TPS651 ◽  
Author(s):  
Tamas Hickish ◽  
Ling-Ming Tseng ◽  
Ajay O. Mehta ◽  
Janice Tsang ◽  
Nadezhda Kovalenko ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Xenograft Model ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Response Duration ◽  
Open Label ◽  
Erbb Family ◽  
Erbb Signaling ◽  
Open Label Phase

TPS651 Background: Management of HER2-overexpressing MBC has improved over the past decade. However, pts still develop resistance to currently available HER2-targeted therapies and novel effective treatments are increasingly required as dual targeted combinations are given in early treatment lines already. Current therapies focus on targeting HER2 and do not inhibit all relevant ErbB Family dimers. Afatinib is an oral, irreversible ErbB Family Blocker that inhibits signaling through activated EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptors and transphosphorylation of ErbB3. Preclinical studies have demonstrated efficacy in T-sensitive and T-resistant human BC xenograft models dependent on ErbB signaling. Efficacy of afatinib in a T-resistant SUM 190 xenograft model has been shown to be increased by addition of IV vinorelbine (V). Afatinib monotherapy has shown promising clinical benefit in 46% of HER2-overexpressing MBC pts who progressed on prior T, with 10% of pts achieving PR. Methods: This open-label Phase II trial (NCT01271725) investigates efficacy and safety of afatinib alone (40 mg/d) followed by afatinib ‘beyond progression’ plus chemotherapy in 120 pts with HER2-overexpressing MBC, who progressed on prior neoadjuvant and/or adjuvant T and/or L. Pts who progress on afatinib monotherapy receive afatinib plus either weekly paclitaxel (P) 80 mg/m2 or V 25 mg/m2. Eligible pts have confirmed HER2-overexpressing BC, stage IV disease measurable by RECIST 1.1, progressed on T and/or L therapy in either neoadjuvant and/or adjuvant setting, are eligible for retreatment with P or V and should not have been pretreated with P (≤12 months) or V, respectively. Exclusion criteria: inadequate cardiac, renal, hepatic and hematological function, pre-existing gastrointestinal dysfunction, rapidly progressing visceral disease, ILD and active brain metastases. The primary endpoint is objective response (OR) and secondary endpoints include best overall response, duration of OR and PFS; safety will be assessed separately for afatinib mono- and combination therapy. Patient enrollment began in May 2011 in ~35 sites and 5 countries.

Phase II trial of sorafenib (bay 43–9006) in patients with advanced anaplastic carcinoma of the thyroid (ATC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6058-6058 ◽  
Author(s):  
G. Nagaiah ◽  
P. Fu ◽  
J. K. Wasman ◽  
M. M. Cooney ◽  
C. Mooney ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
Median Duration ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Median Number ◽  
Anaplastic Carcinoma ◽  
Open Label ◽  
Open Label Phase ◽  
Number Of Cycles

6058 Background: Sorafenib (bay 43–9006) is an oral, small molecule tyrosine kinase inhibitor of the raf-1 protein kinase receptor, VEGFR2 and PDGFR-β with antiangiogenic properties. We are conducting an open label, phase II study of sorafenib in patients with biopsy-proven ATC to evaluate if its objective response rate is >20% and to further characterize its safety profile. Methods: Patients with progressive ATC, after cytotoxic chemotherapy with or without radiation were given sorafenib, on a fixed dosing schedule of 400 mg PO bid on 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or patient refusal. Response was evaluated every 8 weeks with body scans using RECIST criteria. We employed a 2-stage study design: if none of the first 18 patients respond the study is terminated, otherwise accrual is continued to a total of 36 patients at which point if ≤3 of the patients respond, the treatment option is rejected. Results: To date 16 patients (10 male) have enrolled in the study. Median age is 55 years; with (range 28–79). Median time on study is 2 months. Median number of cycles given is 2 (range 1–27). Two of 15 evaluable patients (13%) have partial response (PR) and 4 patients (27%) have stable disease (SD). Median duration of PR/SD is 5.1 months (range 1–24.7months). Median time to progression is 1.5 months. Median duration of survival is 3.5 months (range 1–26 months). All patients at time of reporting are deceased. Most common toxicities are lymphopenia (81%) and fatigue (62%). Grade 3 toxicities include lymphopenia (25%), rash with desquamation, weight loss, and chest pain (all 12%). Grade 4 toxicities include dyspnea (6%) and lymphopenia (6%). There has been no significant cardiovascular toxicity. One patient died on study with rapidly progressive disease. Conclusions: Sorafenib demonstrates objective tumor response in the first 15 evaluable and pretreated patients with advanced ATC. This trial is ongoing and supported in part by NIH grant nos. CA62502. [Table: see text]

A randomized, open-label, phase II study of lapatinib / capecitabine, lapatinib / vinorelbine, or lapatinib / gemcitabine in patients with ErbB2-amplified metastatic breast cancer progressing after taxane treatment: Results of an interim analysis (GLICO-0801 / EGF111792).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11087-e11087
Author(s):  
Henry Leonidas Gomez ◽  
Silvia P. Neciosup ◽  
Celia Tosello ◽  
Patricia Xavier ◽  
Yeni Neron do Nascimento ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Open Label ◽  
Open Label Phase ◽  
Hand Foot Syndrome ◽  
Number Of Cycles

e11087 Background: Lapatinib-capecitabine is approved for the treatment of ErbB2-amplified metastatic breast cancer (MBC) after failure to anthracyclines, taxanes and trastuzumab. GLICO-0801 evaluates different lapatinib-based chemotherapy combinations as 1st/2nd line treatment for ErbB2 amplified MBC progressing after taxane treatment. We present the results of a planned safety interim analysis. Methods: This is an open-label, randomized, international, phase II trial exploring lapatinib (L) 1250mg qd in combination with capecitabine 2000mg/m2 d 1-14 (Arm A) or vinorelbine 25mg/m2 d 1 and 8 (Arm B) or gemcitabine 1000mg/m2 d 1 and 8 (Arm C). Primary objective is to determine the clinical benefit rate (defined as CR+PR+SD for ≥24 weeks). This trial is registered at www.clinicaltrials.gov number: NCT01050322 Results: The first83 randomized patients (pts) (Arm A=29, B=28 and C=26) were included in this analysis. Of them, 65 (78%) have discontinued therapy with mean number of cycles of 4.7, 6.2 and 7.5 in arms A, B and C respectively. Eighteen (21%) pts are still on treatment. Median age was 52y (29-84); 80 pts (96%) had PS 0-1; 51 (61%) were postmenopausal. Fifty-six pts (67%) had visceral metastasis, 52 (63%) were treated as 2nd line therapy and 36 (43%) had received prior trastuzumab. Most reported adverse events (AE) (87%) were grade 1-2. The most common AE (any grade) in arm A: diarrhea 72%, hand-foot syndrome 45%, vomiting 39%, anemia 36%; in arm B: diarrhea 75%, neutropenia 68%, nausea 43%, vomiting 39%; in arm C: diarrhea 72%, neutropenia 60%, anemia 44%, increase in ALT 44%. The most frequent serious AE reported in arm A: diarrhea in 3 pts (10%) and thrombocytopenia in 2 pts (7%); in arm B: febrile neutropenia in 2 pts (7%) and in arm C: sepsis in 1 pt (4%). There was one toxic death related to chemotherapy in arm C. Conclusions: There were no unexpected toxicities so far in this trial with most AEs being mild to moderate and manageable. This interim analysis supports the continuation of the study.

Final report of an open-label phase II trial of bevacizumab plus docetaxel and gemcitabine in metastatic, previously untreated nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18046-e18046
Author(s):  
Nathan A. Pennell ◽  
Sujith R. Kalmadi ◽  
Marc A. Shapiro ◽  
Hamed Daw ◽  
Cristina P. Rodriguez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Final Report ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Open Label Phase

e18046 Background: Platinum and non-platinum doublet chemotherapy has similar efficacy in advanced NSCLC patients (pts). Bevacizumab (B) improves outcomes when added to platinum doublets, but its safety and efficacy in combination with non-platinum doublets is unknown. This study was designed to test the combination of B, docetaxel (D), and gemcitabine (G) in first-line treatment of advanced NSCLC. Methods: Pts with metastatic, non-squamous NSCLC, PS 0-1, and measurable disease by RECIST were enrolled in this open-label, single arm phase II trial. Pts received D (75 mg/m2) on d1, G (900 mg/m2) on d1 & 8, and B (15 mg/kg) on d1 every 21d for up to 6 cycles, followed by B maintenance until progression or 12 mos total. Pts received growth factor d9. CT scans were performed every 6 wks. The primary endpoint was 1-yr progression-free survival (PFS), with secondary endpoints of safety, objective response rate (ORR), overall PFS, and overall survival (OS). Pts with tumor cavitation, untreated brain metastases, and hemoptysis were excluded. Planned enrollment was 46. Results: 13 pts were enrolled from 12/2009 to 4/2011. Pt characteristics: Median age 63 (35-69), 85% male, PS 0 (38%), PS 1 (62%). The median # of cycles of chemotherapy was 6 (1-6), median # cycles of B was 4 (1-15), with 2 pts coming off study prior to the first evaluation (1 grade 5 encephalopathy, 1 grade 4 febrile neutropenia). 5 pts (38%) had chemo dose reduction and 4 (31%) discontinued treatment for toxicity. 3 pts (23%) discontinued B prior to progression, 2 for tumor cavitation and 1 for grade 1 hemoptysis. The grade 3-5 non-hematologic toxicity rate was 69%, with 6 pts (46%) hospitalized with pneumonitis/pneumonia felt possibly related to study drugs. At this point enrollment was halted for safety concerns. The 1-yr PFS was 8%, and the median PFS was 6.9 mos (95% CI 2.0-NYR). 11 pts were evaluable for response, and 6 pts had partial responses for an ORR of 55%. The median OS was NYR with median follow up of 10.9 mos. Conclusions: The combination of B, D, and G was not tolerable at the doses and schedule used in this study. A formal phase I trial is needed if this combination is to be investigated further.

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.

LUX-breast 1: Randomized, phase III trial of afatinib and vinorelbine versus trastuzumab and vinorelbine in patients with HER2-overexpressing metastatic breast cancer (MBC) failing one prior trastuzumab treatment.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS649-TPS649 ◽  
Author(s):  
Nadia Harbeck ◽  
Seock-Ah Im ◽  
Chiun-Sheng Huang ◽  
Young-Hyuck Im ◽  
Binghe Xu ◽  
...  
Keyword(s):  
Objective Response ◽  
Metastatic Breast ◽  
Continuous Treatment ◽  
Phase Iii ◽  
Clinical Activity ◽  
Her2 Positive ◽  
Open Label ◽  
Fresh Tissue ◽  
Oral Vinorelbine ◽  
Erbb Family

TPS649 Background: Afatinib is an ErbB Family Blocker that irreversibly blocks signaling from all relevant ErbB Family dimers. Afatinib is being developed in EGFR (ErbB1)-driven (NSCLC/HNSCC) and HER2 (ErbB2)-driven (breast) malignancies. In trastuzumab-resistant, HER2-positive (SUM190) xenografts, afatinib showed antitumor activity which was superior to lapatinib and increased by addition of IV vinorelbine. Afatinib monotherapy also demonstrated clinical activity (progression-free survival [PFS] = 15.1 wk; objective response [OR] = 10%) in an open-label, single-arm, Phase II trial in patients with HER2-positive MBC after progression on trastuzumab. Methods: LUX-Breast 1 (NCT01125566) is a Phase III, open-label, multicenter trial evaluating the efficacy and safety of afatinib + vinorelbine vs. trastuzumab + vinorelbine in patients with HER2-overexpressing MBC who progressed on, or after one prior trastuzumab-based treatment regimen. Patients are randomized 2:1 to afatinib (40 mg/d oral) + vinorelbine (IV 25 mg/m2/wk) or trastuzumab (IV 2 mg/kg/wk after 4 mg/kg loading dose) + vinorelbine (IV 25 mg/m2/wk). Patients receive continuous treatment in the absence of disease progression or adverse events. Key eligibility criteria include histologically-confirmed HER2-positive BC, stage IV disease; no prior treatment with vinorelbine or HER2-targeted treatment other than trastuzumab; progression on one prior trastuzumab based regimen in either the adjuvant (or <12 months after trastuzumab completion) or first-line (or <6 months after trastuzumab completion) setting; prior anthracycline and/or taxane chemotherapy; ECOG score 0 or 1. The primary endpoint is PFS and secondary endpoints include OR, overall survival and safety. Serum and tissue biomarkers will be assessed on archival tissue. HER-receptor and HER-ligand reprogramming, putative resistance markers and EGFR response signature will be explored in fresh tissue biopsies. Enrollment began in June 2010 and is ongoing, targeting >240 sites with a recruitment target of 780 patients.

A phase II trial of the CDK4/6 inhibitor palbociclib (P) as single agent or in combination with the same endocrine therapy (ET) received prior to disease progression, in patients (pts) with hormone receptor positive (HR+) HER2 negative (HER2−) metastatic breast cancer (mBC) (TREnd trial).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1002-1002 ◽  
Author(s):  
Luca Malorni ◽  
Giuseppe Curigliano ◽  
Alessandro Marco Minisini ◽  
Saverio Cinieri ◽  
Carlo Tondini ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Data ◽  
Single Agent ◽  
Objective Response ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Complete Response ◽  
Clinical Activity ◽  
P Value ◽  
Open Label

1002 Background: P is approved for treatment of HR+/HER2− mBC combined with ET. There is paucity of clinical data of single-agent P in ET resistant pts. Pre-clinical data suggest P may partially reverse endocrine resistance, though this is yet to be tested in pts. Methods: This Phase II, open-label, multicenter study enrolled post-menopausal pts with HR+ HER2− mBC who progressed on 1 or 2 prior ETs. Pts were randomized to P (125 mg/d 3 w on/1 w off) alone or to continue their current ET (aromatase inhibitor or fulvestrant) in combination with P (same schedule as P arm). The primary endpoint was clinical benefit rate (CBR) [complete response (CR), partial response (PR) and stable disease (SD) for > 6 months (mo)]. Secondary endpoints were adverse events (AE) and additional measures of efficacy. A two-stage optimal design assessed treatment activity in each arm assuming activity as CB≥40% (α and β = 10%). Exploratory comparisons were planned for safety and efficacy endpoints. Results: 115 pts were enrolled (ITT population) 58 in the P arm and 57 in the P+ET arm. In both arms, 67% of pts had the study treatment as second line ET, 33% as third line, and about 1/3 of pts also received 1 prior chemotherapy for mBC. CBR was similar in both arms: 54% (95% CI 42 - 67%) with P+ET, and 60% (95% CI 48 -73%) with P alone. Median duration of CB was longer with P+ET (11.5 mo; 95% CI 8.6 – 17.8) than with P (6 mo; 95% CI 3.9 - 9.9) (HR 0.31, 95% CI 0.1 - 0.7, p-value 0.001, exploratory). Objective response rate (ORR; CR, PR) was 11% (95% CI 3 - 19%) and 7% (95% CI 0.4 -13%) with P+ET and P, respectively. PFS was 10.8 mo (95% CI 5.6 - 12.7) with P+ET and 6.5 mo (95% CI 5.4 - 8.5) with P alone (HR 0.69, 95% CI 0.4 - 1.1, p-value 0.13, exploratory). AEs were in line with previous data. Conclusions: Single agent P has clinical activity in ET pre-treated HR+/HER2– mBC pts. The observed increase in PFS and duration of CB with P+ET may suggest that P could reverse resistance to the prior line of ET. Translational studies are ongoing to explore potential biomarkers in this setting. Clinical trial information: NCT02549430.

Recombinant humanized anti-PD-1 monoclonal antibody (JS001) in patients with refractory/metastatic nasopharyngeal carcinoma: Interim results of an open-label phase II clinical study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6017-6017 ◽  
Author(s):  
Fenghua Wang ◽  
Xiao-Li Wei ◽  
Ji Feng Feng ◽  
Qi Li ◽  
Nong Xu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Response ◽  
Phase Ii ◽  
Copy Number ◽  
Objective Response ◽  
Nasopharyngeal Cancer ◽  
Dna Copy Number ◽  
Open Label ◽  
Open Label Phase ◽  
Ebv Dna

6017 Background: Metastatic nasopharyngeal cancer (NPC) patients progressed afterstandardtherapy have limited treatment options. Toripalimab, also known as JS001, a humanized IgG4 antibody specific for human PD-1, has been approved for 2nd line treatment of metastatic melanoma in China. Here we report the results from a phase IIstudy in metastatic NPC patients treated with toripalimab.(Clinical trial ID: NCT02915432). Methods: This multi-center, open-label, phase II registration study is designed to evaluate the safety and efficacy of toripalimab in metastaticNPC patients who have failed systemic treatment. Toripalimabis given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity.Tumor PD-L1 expression, plasma EBV DNA level and other biomarkerswill be correlatedwith clinical response. Results: Enrollment of 190chemo-refractory metastatic NPCpatients was completed by Feb 2019 from 17 participating centers. The median age was 46 years, with 89.5% patients received at least 2 lines of prior systemic therapies. Treatment related adverse events (TRAE)occurred in 92% patients, which were mostly grade 1 or 2.Common TRAE includedanemia, hypothyroidism, AST increased, proteinuria, pyrexia, cough, constipation, ALT increased, hypoalbuminemia and pruritus.Grade 3 or higherTRAEoccurred in 25% patients.By the cut-off date of Jan 7 2019, among 135 evaluable patients, 3 complete responses, 31 partial responses and 40 stable diseaseswere observed for an objective response rate (ORR) of 25.2% and a disease control rate of 54.8%. PD-L1 expression results were obtained from 125 patients and 45.6% (57/125) were PD-L1+.PD-L1+ patientsachieved slightly higherORR than PD-L1- patients, 29.8% versus 22.1%. In addition, an average drop of 47-fold plasma EBV DNA copy number was observed in responding patients, which typically proceeded the radiographic identification of clinical benefit. Conclusions: Toripalimab has demonstrated a manageable safety profileand encouraging clinical activity in the largest check-point blockade study in NPC to date. A change in plasma EBV DNA copy number might serve as a predictive marker for favorable clinical response. Patients will be continuously monitored for additional safety and survival readouts. Clinical trial information: NCT02915432.

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