Association of tumor mutational burden (TMB) and clinical outcomes with pembrolizumab (pembro) versus chemotherapy (chemo) in patients with metastatic triple-negative breast cancer (mTNBC) from KEYNOTE-119.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
Eric P. Winer ◽  
Oleg Lipatov ◽  
Seock-Ah Im ◽  
Anthony Goncalves ◽  
Eva Muñoz-Couselo ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cox Regression ◽  
Single Agent ◽  
Positive Association ◽  
Open Label ◽  
P Values ◽  
Systemic Treatments ◽  
Number Of Patients ◽  
Open Label Phase ◽  
Tumor Mutational Burden

1013 Background: In the randomized, open-label, phase 3 KEYNOTE-119 study (NCT02555657) , OS was not significantly different with pembro monotherapy versus chemo in second- or third-line settings for mTNBC; however, the pembro treatment effect increased with increasing PD-L1 enrichment. We evaluated the association of TMB with efficacy of pembro monotherapy versus chemo in patients with previously treated mTNBC. Methods: Patients with centrally confirmed TNBC and 1 or 2 prior systemic treatments for metastatic disease were enrolled. Patients were randomly assigned 1:1 to pembro 200 mg Q3W or single-agent chemo per investigator’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine. Association of TMB, as measured by FoundationOne CDx (Foundation Medicine), with response was an exploratory objective evaluated using receiver operator characteristic (ROC) analysis, logistic regression (ORR), and Cox regression (OS; PFS) within treatment arms; estimates of efficacy based on TMB cutpoint used a prespecified cutpoint of 10 mut/Mb. Results: TMB data were available for 253/601 (42.1%) treated patients (pembro, n = 132; chemo, n = 121); baseline characteristics were similar to that of the overall study population. One-sided P values for the association of TMB and clinical outcomes in pembro-treated patients were 0.154 for ORR, 0.014 for PFS, and 0.018 for OS; the area under the ROC curve ([AUROC] 95% CI) for predicting ORR was 0.58 (0.43-0.73). Two-sided P values for the association of TMB and clinical outcomes in chemo-treated patients were 0.114 for ORR, 0.478 for PFS, and 0.906 for OS; AUROC (95% CI) was 0.43 (0.27-0.59). Twenty-six patients had TMB ≥10 mut/Mb. Thus, the prevalence of TMB ≥10 mut/Mb was ~10%. Outcomes based on TMB cutpoint are reported in the Table. Conclusions: Data from this exploratory analysis from KEYNOTE-119 suggest a potential positive association between TMB and clinical benefit with pembro but not chemo in patients with mTNBC. Although precision is limited by sample size and the number of patients with TMB ≥10 mut/Mb, ORR and HRs for OS suggested a trend towards increased benefit with pembro versus chemo in patients with TMB ≥10 mut/Mb. Clinical trial information: NCT02555657 . [Table: see text]

Health-related quality of life (HRQoL) of pembrolizumab (pembro) versus physician choice single-agent paclitaxel, docetaxel, or irinotecan in subjects with advanced/metastatic adenocarcinoma (ACC) or squamous cell carcinoma (SCC) of the esophagus that has progressed after first-line standard therapy (KEYNOTE-181).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4048-4048 ◽  
Author(s):  
Antoine Adenis ◽  
Amit Kulkarni ◽  
Gustavo Colagiovanni Girotto ◽  
Christelle De La Fouchardiere ◽  
Helene Senellart ◽  
...  
Keyword(s):  
Cox Regression ◽  
Single Agent ◽  
Open Label ◽  
P Values ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Related Quality ◽  
Eortc Qlq C30 ◽  
Health Related ◽  
Eortc Qlq

4048 Background: KEYNOTE-181 (NCT02564263) is an open-label, randomized, phase 3 trial in ACC and SCC of the esophagus that evaluated IV pembro 200 mg Q3W for up to 2 years vs investigator choice of single-agent paclitaxel/docetaxel/irinotecan (control). Pembro was superior to control for OS in patients with PD-L1 CPS ≥10 (N = 222; median 9.3 vs 6.7 months; P= 0.0074). Here we present results of prespecified HRQoL analyses in this population. Methods: The EORTC QLQ-C30 and EORTC QLQ-OES18 were administered at baseline; weeks 2, 3, 4, 6, 9, 12, 18; every 9 weeks up to 1 year/end of treatment; and 30-day safety follow-up visit. Data from patients receiving ≥1 dose of study treatment and completing ≥1 HRQoL assessment were analyzed. Least squares mean (LSM) score change from baseline to week 9, 95% CI, and nominal P values were calculated. Time to deterioration (TTD) (≥10-point decline from baseline) was assessed by Kaplan-Meier method and Cox regression model. HRs, 95% CIs, and nominal P values are provided. Results: The HRQoL population included 218 PD-L1 CPS ≥10 patients (107 pembro, 111 control). QLQ-C30 compliance at week 9 was 88.9% for pembro and 83.9% for control. There was no significant difference in LSM between arms (3.68; 95% CI –2.28, 9.64; P= 0.2248) in global health status (GHS)/QoL score. Week 9 QLQ-OES18 compliance was 88.4% for pembro and 83.3% for control. QLQ-OES18 scores were not significantly different between arms. TTD for pain (HR 1.02; 95% CI 0.58, 1.81; P= 0.5282), reflux (HR 1.69; 95% CI 0.83, 3.47; P= 0.9254), and dysphagia (HR 1.81; 95% CI 0.97, 3.37; P= 0.9693) subscales were not significantly different between arms. Conclusions: Over 9 weeks, patients treated with pembro had stable GHS/QoL scores similar to those of patients treated with single-agent docetaxel/paclitaxel/irinotecan. Combined with the superior OS and lower rate of treatment-related AEs seen with pembro, these data support clinically meaningful benefit of pembro in esophageal cancer patients with PD-L1 CPS ≥10. Clinical trial information: NCT02564263.

scholarly journals Dasatinib as a Single Agent in Triple-Negative Breast Cancer: Results of an Open-Label Phase 2 Study

2011 ◽  
Vol 17 (21) ◽  
pp. 6905-6913 ◽  
Author(s):  
Richard S. Finn ◽  
Carmelo Bengala ◽  
Nuhad Ibrahim ◽  
Henri Roché ◽  
Joseph Sparano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Study ◽  
Open Label Phase

scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

scholarly journals Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study

2020 ◽  
Vol 10 (10) ◽  
Author(s):  
Paul G. Richardson ◽  
Hans C. Lee ◽  
Al-Ola Abdallah ◽  
Adam D. Cohen ◽  
Prashant Kapoor ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Pathological Finding ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Blurred Vision ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Duration Of Response

Abstract DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3–72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8–not reached [NR]); median progression-free survival was 5.7 months (2.2–9.7); median overall survival was not reached (8.7 months–NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.

scholarly journals RBTT-01. A PHASE 2 TRIAL WITH ABI-009 (NAB-SIROLIMUS) AS SINGLE-AGENT AND COMBINATIONS IN RECURRENT HIGH-GRADE GLIOMA (rHGG) AND IN NEWLY DIAGNOSED GLIOBLASTOMA (ndGBM)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi218-vi219 ◽  
Author(s):  
Santosh Kesari ◽  
Tiffany Juarez ◽  
Jose Carrillo ◽  
Judy Truong ◽  
Minhdan Nguyen ◽  
...  
Keyword(s):  
Single Agent ◽  
Mtor Inhibitors ◽  
High Grade Glioma ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Promising Target ◽  
Open Label Phase ◽  
Newly Diagnosed Glioblastoma ◽  
Cns Penetration

Abstract BACKGROUND The mTOR pathway is frequently activated in patients with GBM and is associated with reduced survival, making this pathway a promising target. However, mTOR inhibitors, including everolimus and temsirolimus, have poor brain penetration, limiting their potential use for GBM. ABI-009 is a novel albumin-bound mTOR inhibitor that has a distinct PK profile and biodistribution, including CNS penetration. The goal of this prospective, multi-cohort open-label phase 2 study is to evaluate the efficacy and safety of ABI-009 monotherapy and combination therapy in rHGG and ndGBM. METHODS Eligible patients are ≥18 years old, KPS score ≥70, and have histologically confirmed rHGG or ndGBM. Arm A has 5 cohorts in patients with rHGG, naïve to mTOR inhibitors: 1) ABI-009 single agent IV 100 mg/m2; 2–5) ABI-009 60mg/m2 plus TMZ 50mg/m2 or BEV 5mg/kg or marizomib 0.8mg/m2 or CCNU 90mg/m2. In Arm B for patients with ndGBM, ABI-009 100mg/m2 is given weekly for 4 weeks (Induction) after surgery, followed by ABI-009 at 60mg/m2 plus RT/TMZ. Up to 19 patients per cohort will be enrolled: initial 9 patients with a stopping rule that only if there are ≥2 responses will the study proceed to further enrollment of the next 10 patients (Simon’s 2-stage design). Treatment will continue until disease progression or unacceptable toxicity. The primary endpoint for all cohorts is overall response rate per RANO criteria; secondary endpoints are median PFS and OS, 6-month and 12-month PFS, 12-month OS, and safety. This study is open and actively enrolling patients. The anticipated enrollment period is 24 months. NCT03463265

scholarly journals OS4.1 MEVITEM: A European, randomized, open-label, Phase I/II study of vismodegib in combination with temozolomide versus temozolomide alone in adult patients with recurrent or refractory medulloblastoma presenting an activation of the Sonic Hedgehog (SHH) pathway

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii10-iii10
Author(s):  
D Frappaz ◽  
M Barritault ◽  
L Montané ◽  
F Laigle-Donadey ◽  
O Chinot ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Type I Error ◽  
Single Agent ◽  
Objective Response ◽  
Progression Rate ◽  
Type I ◽  
Filamin A ◽  
Open Label ◽  
Shh Pathway ◽  
Open Label Phase

Abstract BACKGROUND Vismodegib (V) suppresses sonic hedgehog (SHH) signaling. We postulated that vismodegib together with chemotherapy may be more efficient than chemotherapy alone in patients (pts) relapsing of a SHH-activated medulloblastoma (MB). MATERIAL AND METHODS Adult pts with recurrent SHH-MB not previously exposed to temozolomide (T) were randomly assigned (2:1 ratio) to Arm A (V daily 150mg/d, po) + T (D1-5: 150 mg/m2 for cycle 1 and 200 mg/m2 thereafter; n=up to 25pts) or Am B (T alone; n=up to 13pts). Identification of SHH activation was performed centrally by IHC (GAB1, β-catenin, filamin A, and YAP1). NGS analyses were performed to identify the mutations responsible for SHH activation. Primary objectives were to assess the incidence of severe toxicities (safety run-in based on a 3 + 3 design) and the 6-month non-progression rate (NPR-6m) according to WHO criteria and based on central read tumor assessment (Phase II). A Minimax Simon’s two-stage design was used to detect NPR-6m of 55% (p0: 30%, type I error rate of 5%, power of 80%). At first stage, ≥ 3/9 pts without progression at 6m were required for the accrual of 16 additional pts in Arm A. A 3rd independent and parallel arm with V as single agent (Arm C, n= up to15pts) was added for pts previously treated by T. RESULTS 24 SHH-MB pts were enrolled (Arm A: 10, Arm B: 5 and Arm C: 9; median age: 37 y [21–55]). At the end of the safety run-in; no major safety concerns were reported. At the end of Stage I: no objective response were reported and 2 pts among 10 were free of progression at 6m among in Arm A. According to statistical rules, the study was definitively closed to enrolment. NGS analyses showed a PTCH1 inactivating mutation in 6 pts (n=4 in arm A; n= 2 in arm B); a SMO activating mutation in 4 pts (n= 3 in Arm A; n=1 in Arm B). For 1 pt in each arm, no tumor sample was available for analysis, for 1 pt in Arm A DNA quality was insufficient, and for 1 patient in each arm no mutations of SMO, PTCH1, SUFU or SHH were found. Out of the 4 pts in Arm A with an inactivating PTCH1 mutation, only 1 was progression free at 6m. PFS and OS data will be presented at the meeting. CONCLUSION The combination of vismodegib with monthly T failed to demonstrate superior activity as compared with T alone. Further studies are warranted to refine therapeutic indication for vismodegib

Phase II Study of Carboplatin, Paclitaxel, and Bevacizumab With Maintenance Bevacizumab As First-Line Chemotherapy for Advanced Müllerian Tumors

2010 ◽  
Vol 28 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Richard T. Penson ◽  
Don S. Dizon ◽  
Stephen A. Cannistra ◽  
Maria R. Roche ◽  
Carolyn N. Krasner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Open Label ◽  
Peritoneal Cancer ◽  
Open Label Phase

Purpose New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. Patients and Methods An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage ≥ IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m2 IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. Conclusion The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.

Phase II trial of panobinostat (LBH589) in patients (pts) with refractory metastatic colorectal cancer (MCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 582-582 ◽  
Author(s):  
Philip Jordan Gold ◽  
David A. Smith ◽  
Desiree Iriarte ◽  
Barry Boatman ◽  
Henry G. Kaplan
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Ecog Performance Status ◽  
Treatment Regimes ◽  
Open Label Phase ◽  
Secondary Endpoints

582 Background: LBH589 is a novel histone deacetylase inhibitor (HDACi) which induces apoptosis of tumor cells. LBH589 has been shown to cause regression of colon cancer in animal models and phase I trials have shown the agent to be well tolerated, providing rationale for studying this agent in pts with MCRC. Methods: This was a multicenter, open-label phase II study of single agent LBH589 in patients with MCRC who failed at least 2 prior regimens for metastatic disease. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Pts received LBH589 30mg po on M/W/F until disease progression. Pts were evaluated for toxicity every 2 weeks and for response every 8 weeks. The primary endpoint was overall survival. Secondary endpoints included response rate, time to progression (TTP), and toxicity. Results: 29 pts were enrolled (16 male, 13 female). The median age was 59 (range 41-76). The median number of prior treatment regimes was 3 (2-11). The median survival was 5.1 months (range 1-24+). There were no objective responses. 3 pts had SD at 8 weeks. The median TTP was 7.7 weeks (range 1-38.). Six pts had grade 4 thrombocytopenia requiring platelet transfusion. Nine pts required dose reductions for toxicity. Conclusions: Single-agent LBH589 was not associated with objective tumor responses in this heavily pre-treated pt population. However, the median survival was comparable to that seen in other trials of single agent targeted therapy in the treatment of refractory MCRC. Thrombocytopenia was significant, and may complicate potential trials of combination therapy.

A randomized, open-label phase II study of single-agent vintafolide versus vintafolide plus docetaxel versus docetaxel alone in second-line NSCLC patients with all target lesions expressing folate-receptor (TARGET).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS8125-TPS8125
Author(s):  
Martin J. Edelman ◽  
Hong Ma ◽  
Wendy Perez ◽  
Alex A. Adjei ◽  
Nasser Hanna
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Folate Receptor ◽  
Single Agent ◽  
Primary Objective ◽  
Second Line ◽  
Open Label ◽  
Histologic Diagnosis ◽  
Potential Biomarker ◽  
Open Label Phase

TPS8125 Background: Folate receptor (FR) is frequently overexpressed in NSCLC and is a potential biomarker for therapy selection. Vintafolide (EC145) is designed to target FR expressing cells and consists of folate linked to desacetylvinblastinehydrazide. The FR targeted imaging agent, 99mTc-etarfolatide (EC20), consists of folate coupled to technetium and identifies lesions that overexpress FR which may respond to vintafolide treatment. A phase II study of single-agent vintafolide in heavily pre-treated lung adenocarcinoma patients (pts) showed promising activity in clinical benefit response (50% vs. 14.3%) and overall survival (OS, 47.2 wks vs. 14.9 wks), in pts whose target lesions all expressed FR [FR (100%)] vs pts whose target lesions were not all FR positive (Edelman et al, JTO 2012:7:1618-21). This trial assesses the benefit of vintafolide as second-line therapy in NSCLC FR (100%) pts. Methods: This is a randomized, open-label phase II study of vintafolide vs. vintafolide + docetaxel vs. docetaxel in second line NSCLC FR (100%) pts ( NCT01577654 ). Key eligibility criteria include: cytologic or histologic diagnosis of NSCLC, 1 prior systemic therapy for advanced disease, and PS 0-1. At baseline, pts undergo 99mTc-etarfolatide imaging to detect FR-positive lesions. FR (100%) pts are randomized 1:1:1 to vintafolide, vintafolide + docetaxel, or docetaxel. Vintafolide (2.5 mg) is administered on d 1, 4, 8, and 11 of a 3-wk cycle. Docetaxel (75 mg/m2) is given on d 1 of a 3-wk cycle. Treatment continues until disease progression or unacceptable toxicity. Pts receiving vintafolide + docetaxel who discontinue docetaxel due to toxicity may continue vintafolide alone. Disease status is evaluated by RECIST v1.1 criteria every 6 wks and adverse events are monitored throughout. The primary objective of this study compares PFS between the docetaxel control arm and each experimental arm with the goal of demonstrating a hazard ratio of ≤0.67 favoring the experimental arms. Secondary objectives include response rate, disease control rate, OS, and safety/tolerability. Enrollment to the study is ongoing. Clinical trial information: NCT01577654.

A randomized, controlled, open label phase II study of erlotinib (E) with or without the MET antibody emibetuzumab (Emi) as first-line treatment for EGFRmt non-small cell lung cancer (NSCLC) patients who have disease control after an 8-week lead-in treatment with erlotinib.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9019-9019 ◽  
Author(s):  
Giorgio V. Scagliotti ◽  
Denis Moro-Sibilot ◽  
Jens Kollmeier ◽  
Adolfo G. Favaretto ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Disease Control ◽  
Single Agent ◽  
Stage Iv ◽  
Exploratory Analysis ◽  
Clinical Activity ◽  
Open Label ◽  
Egfr Inhibition ◽  
Significant Difference ◽  
Open Label Phase ◽  
Ecog Ps

9019 Background: MET expression is a mechanism of resistance to EGFR inhibition in EGFRmt NSCLC and correlated with poor prognosis. Emi (LY2875358) is a humanized IgG4 monoclonal bivalent MET antibody that blocks ligand dependent and independent HGF/MET signaling. This Phase 2 study compared the clinical activity of Emi + E versus single agent E in 1st line EGFRmt metastatic NSCLC. Methods: Stage IV, EGFRmt NSCLC pts with disease control following an 8-week lead-in E (150 mg PO QD) treatment were randomized 1:1 to receive Emi (750 mg IV Q2W) + E or E alone. Pts were stratified by ECOG PS, ethnicity, MET expression status, and response at the end of the lead-in. The primary endpoint was PFS from randomization. Additional endpoints included safety, OS, PK, and exploratory analysis of MET-expressing populations. Results: Out of181 pts enrolled, 141 pts were randomized (Emi+E: 71; E: 70). In the ITT population, median PFS for EMI+E was 9.3 months (m) compared with 9.5 m for E (HR = 0.89: 90% CI 0.64-1.23; p = 0.534). Exploratory analysis of MET-high expressing pts (MET 3+ expression in ≥90% of tumor cells; n = 24 pts) showed a 15.3 m improvement in PFS (EMI+E: 20.7 m; E: 5.4 m [HR: 0.39; 90% CI: 0.17-0.91]). No difference in PFS was observed in the complementary population (HR: 1.1 [90% CI: 0.7-1.7]). Similar frequencies of related AEs were reported for both treatment arms. Drug-related TEAEs that were more frequent ( > 10%) for Emi+E were peripheral edema and fatigue (all grade 1 or 2). Emi serum concentrations were consistent with previously obtained PK results, and no apparent exposure-response was observed. Median OS in the ITT population was not achieved (NA) for either arm. In MET-high expressing pts, median OS was 20.6 m for E (90% CI: 8.87, NA) whereas it was not achieved for Emi+E (90% CI: NA, NA). Conclusions: No statistically significant difference in PFS was noted in the ITT population.Exploratory analysis confirmed that high MET expression is a negative prognostic marker for pts treated with E and indicated that these pts may receive clinically meaningful benefit from Emi+E. Clinical trial information: NCT01897480.

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