bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanded phase I study of intratumoral Ad-RTS-hIL-12 plus oral veledimex: Tolerability and survival in recurrent glioblastoma.
Authors: Chiocca E. Antonio , Yu John , Phuphanich Surasak , Lukas Rimas Vincas , Kumthekar Priya , Yang Yijun , Zhou Qiang (John) , Buck Jill Y. , Deary Alicia , Cai Hongliang , Barrett John A. , Cooper Laurence JN , Lebel Francois M. 
Published: September 2018

2044 Background: Glioblastoma (GBM) is an aggressive brain tumor affecting ~74,000 people worldwide annually. Recurrent GBM patients have a median OS (mOS) of 6-7 months. OS in patients who have failed temozolomide, bevacizumab or equivalent salvage chemotherapy, is ~3-5 months. New therapies are urgently needed. Ad-RTS-hIL-12 (Ad) is a novel gene therapy expressing IL-12 under the control of an oral activator ligand, veledimex (V), through the RheoSwitch Therapeutic System. Intratumoral administration of Ad results in targeted tumor cytotoxicity and induction of systemic T cell memory. Ad + V is a treatment strategy to extend the IL-12 therapeutic window. Methods: In a multicenter Phase I dose escalation trial and expansion cohort, subjects with recurrent or progressive Grade III or IV glioma undergoing resection were injected intratumorally with Ad 2 x 1011 viral particles and daily oral V for 15 doses, beginning prior to surgery. The primary endpoint is safety and tolerability of Ad + V; secondary endpoints include OS. Results: 25 subjects were dosed in 3 dose escalation cohorts: 20 mg (n = 7), 30 mg (n = 4), and 40 mg (n = 6) and an expansion cohort of 20 mg (n = 8). Results show V crossed the blood brain-barrier with 35±5% of plasma levels detected in the brain tumor. The 20 mg dose (n = 15) had better drug compliance (86%) than the 30 mg (63%) or 40 mg (52%) cohorts and the 20 mg cohort shows better survival (mOS 12.7 months) compared to other cohorts. The frequency of related ≥Grade (G)3 AEs in the 20 mg cohort was significantly lower: 20% in 20mg, 50% in 30mg and 40 mg. In the 20 mg cohort, the most frequent AEs were transient mild flu-like symptoms seen in 12/15, G3 cytokine release syndrome in 2/15, G3 elevated ALT/AST in 1/15 and G3 lymphopenia in 3/15. All AEs reversed promptly upon discontinuing V. Conclusions: Overall, Ad + 20 mg V is well tolerated; toxicities were predictable and reversible upon discontinuing V. There is a correlation between V dose, BBB penetration and drug related AEs. The tolerability and encouraging survival observed to date warrant further investigation in a pivotal trial. A stereotactic arm and a pediatric trial in diffuse intrinsic pontine glioma patients are planned. Clinical trial information: NCT02026271.
An investigator-initiated phase I study of ONX-0801, a first-in-class alpha folate receptor targeted, small molecule thymidylate synthase inhibitor in solid tumors.
Authors: Banerji Udai , Ingles Garces Alvaro Henrique , Michalarea Vasiliki , Ruddle Ruth , Raynaud Florence I. , Riisnaes Ruth , Nava Rodrigues Daniel , Tunariu Nina , Porter Joanna C , Ward Sarah Emily , Parmar Mona , Turner Alison Joanne , Seeramreddi Satyanarayana , Hall Emma , Dean Emma Jane , Basu Bristi , George Angela , Kaye Stan B , Banerjee Susana N. , De Bono Johann S. 
Published: September 2018

2503 Background: ONX-0801 is a first-in-class alpha folate receptor (AFR) targeted thymidylate synthase inhibitor, engineered to differentially accumulate 6000-fold in AFR overexpressing cancer cells. Methods: A 3+3 dose escalation design was used and two IV schedules were explored. Schedule A, weekly dosing (QW) and schedule B, once every 2 weeks dosing (Q2W). A cycle consisted of 4 weeks and treatment was stopped after 6 cycles in both schedules. An expansion cohort to evaluate clinical activity in patients with AFR overexpressing high grade serous ovarian cancer (HGSOC) was planned. Results: 21 patients each were treated in schedule A and B exploring doses ranging from 1-6 mg/m2 and 2-12 mg/m2, respectively. The dose limiting toxicity on schedule A was G3 cellulitis; no dose limiting toxicity was seen on schedule B. The most common toxicities were fatigue 15/42 (36%), nausea 9/42 (21%) and dysgeusia 5/42 (12%). Within schedule A at 4 mg/m2, 2 patients developed suspected drug-related changes on pulmonary function tests (drop in Dlco > 15%) at cycles 5 and 6, respectively. No cases of suspected drug-related drop in Dlco were noted in patients treated in schedule B. No grade 3-4 diarrhea, mucositis or neutropenia were seen in either cohort. The Cmax, AUC and half-life at 12 mg/m2 were 4952 ng/mL, 85170 h*ng/mL and 26 h, respectively. Pre-clinical PK-PD modelling aimed to achieve concentrations between 0.05-1 µM and this was achieved for periods of 48 h at doses of 4 mg/m2and above. Based on safety and PK, the recommended phase II dose (RP2D) of ONX-0801 was 12 mg/m2 Q2W and an expansion in patients with HGSOC is ongoing. 5 patients with HGSOC had partial responses (PRs) in the dose escalation cohort. In the current expansion cohort in patients with HGSOC, 5/11 patients had PRs. Archival samples have been analyzed from 8/11 patients in the expansion cohort. 4/4 AFR+ve and 4/4 AFR-ve patients did and did not have a PR following treatment with ONX-0801, respectively. Conclusions: The RP2D of ONX-0801 is 12 mg/m2 Q2W. At the RP2D, multiple patients with AFR overexpressing HGSOC have had PRs and further randomized biomarker prespecified phase II trials are warranted. Clinical trial information: NCT02360345.
Phase I study of ABBV-399, a c-Met antibody-drug conjugate (ADC), as monotherapy and in combination with erlotinib in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Angevin Eric , Strickler John H. , Weekes Colin D. , Heist Rebecca Suk , Morgensztern Daniel , Nemunaitis John J. , Fan Xiaolin , Beaulieu Juliette , Motwani Monica , Afar Daniel E. , Naumovski Louie , Kelly Karen 
Published: September 2018

2509 Background: The c-Met receptor is overexpressed in ~50% of pts with NSCLC. ABBV-399 is a first-in-class ADC composed of ABT-700, an anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). Preclinical data demonstrate that ABBV-399 can deliver a potent cytotoxin directly to c-Met+ tumor cells. Methods: ABBV-399 was administered at doses ranging from 2.4 to 3.0 mg/kg (dose expansion and combination cohorts at 2.7 mg/kg) once every 21 days to 29 pts with advanced c-Met+ (immunohistochemistry [IHC] H-score ≥150) NSCLC both as monotherapy (ABBV-399/monoT; 16 pts) and in combination with oral erlotinib 150 mg daily (ABBV-399/ERL; 13 pts) (NCT02099058). c-Met overexpression was assessed by IHC utilizing the SP44 antibody (Ventana; Tucson, AZ, USA). Results: As of January 9, 2017, 16 pts with c-Met+ NSCLC received ≥1 dose of ABBV-399/monoT. Monotherapy treatment-related adverse events (TRAEs) occurring in ≥10% of pts (all dose levels and all grades) were fatigue (43.8%), nausea (37.5%), neuropathy (25.0%), vomiting (18.8%), and anemia, constipation, and diarrhea (12.5% each). Three of 16 (19%) ABBV-399–treated c-Met+ NSCLC pts had a confirmed partial response (PR) with duration of response (DOR) 3, 4.5, and 10+ months. At week 12, 6 of 16 pts (37.5%) had disease control. TRAEs in ABBV-399/ERL occurring in ≥10% of pts (all grades) were neuropathy (30.8%), and acneiform rash, diarrhea, fatigue, nausea, and dry skin (15.4% each). Four of 13 (31%) evaluable ABBV-399/ERL–treated c-Met+ pts had a PR (3 confirmed, 1 unconfirmed) with DOR 1+, 2.7, 5.3+, and 11+ months. Three of the 4 pts with PR had EGFR-mutated tumor and recently progressed on TKI. At week 12, 8 of 13 pts (61.5%) had disease control. There were no treatment-related deaths as monotherapy or in combination with erlotinib. Responses were seen in both squamous and non-squamous histology. Conclusions: ABBV-399 is well tolerated at 2.7 mg/kg once every 21 days and has demonstrated antitumor activity in pts with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Updated efficacy/safety data and MET gene status will be presented. Clinical trial information: NCT02099058.
Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy.
Authors: Bernatchez Chantale , Haymaker Cara L. , Hurwitz Michael E. , Kluger Harriet M. , Tetzlaff Michael T. , Jackson Natalie , Gergel Ivan , Tagliaferri Mary Ann , Zalevsky Jonathan , Hoch Ute , Fanton Christie , Iacucci Ernesto , Aung Sandra , Imperiale Michael , Liao Ej , Bentebibel Salah E , Tannir Nizar M. , Hwu Patrick , Sznol Mario , Diab Adi 
Published: September 2018

2545 Background: NKTR-214 is a CD122-biased agonist designed to provide sustained signaling through the heterodimeric IL-2 receptor pathway (IL-2Rβɣ) to preferentially activate and expand effector CD8+ T and NK cells over T regulatory cells in the tumor microenvironment. Immune changes in the tumor microenvironment after NKTR-214 treatment was assessed in patients with locally advanced or metastatic solid tumors. Methods: NKTR-214 was administered IV in an outpatient setting q2w or q3w. Serial blood and tumor tissue samples were collected to measure immune activation using immunophenotyping including flow cytometry, immunohistochemistry (IHC), T cell clonality and gene expression analyses. Results: 26 patients (pts) have been treated with NKTR-214 at q3w, 4@0.003, 9@0.006, 6@0.009 and 1@0.012 mg/kg. Six pts received 0.006 mg/kg q2w. 58% of pts had prior immunotherapy. The most common Gr1-2 TRAEs were fatigue (73%) and pruritus (65%), and decreased appetite (46%). One pt experienced Gr3 syncope and hypotension at the highest dose tested and continued treatment at a lower dose. No drug-related AEs led to study discontinuation. No immune-related AEs or capillary leak syndrome were observed. 6 pts (23%) experienced tumor shrinkage from 10-30%. Three immunotherapy naïve pts receiving sequential anti-PD1 therapy, after ending treatment with NKTR-214, experienced significant tumor regression at first scan. In all pts evaluated, blood samples showed increases in newly proliferating (Ki67+) T and NK cells 8 days post dose. Flow cytometry and/or IHC revealed an up to 10-fold increase from baseline in tumor CD8+T and NK cells in the tumor microenvironment, with minimal changes to Tregs. PD-1 expression increased 2-fold in TILs. Gene expression analysis of tumor tissue showed increases in several immune checkpoint genes, cytotoxic markers (IFNg, PRF1, and GZMB), as well as a dynamic change in T cell clonality. Conclusions: Based on a favorable safety profile and strong correlative biomarker data, a phase 1/2 trial combining NKTR-214 and nivolumab is currently enrolling. Clinical trial information: NCT02869295.
First-in-human phase I study of an oral HSP90 inhibitor, TAS-116, in advanced solid tumors.
Authors: Yanagitani Noriko , Horiike Atsushi , Kitazono Satoru , Ohyanagi Fumiyoshi , Kondo Shunsuke , Shimomura Akihiko , Fujiwara Yutaka , Doi Toshihiko , Kuboki Yasutoshi , Kawazoe Akihito , Shitara Kohei , Ohno Izumi , Banerji Udai , Sundar Raghav , Ohkubo Shuichi , Huang Jerry M. , Nishio Makoto , Yamamoto Noboru 
Published: September 2018

2546 Background: TAS-116 is an oral non-ansamycin, non-purine, and non-resorcinol highly selective inhibitor of HSP90α/β. The objective of this FIH study was to determine the MTD and investigate the safety, tolerability, PK, PD (HSP70 protein levels in PBMCs), and antitumor activity of TAS-116. Methods: The study is being conducted in Japan and the UK. Patients with advanced solid tumors received escalating doses of TAS-116 once daily (QD) with an accelerated titration design. After the MTD was determined, safety and tolerability of 5 days on / 2 days off per week administration (QDx5) at the MTD in QD was explored. In parallel, the MTD with every other day administration (QOD) was evaluated by using a 3 + 3 design. Results: As of 20 September 2016, 52 patients were enrolled. TAS-116 was evaluated at doses of 4.8 to 150.5 mg/m2/day in the QD schedule and doses of 107.5 to 295.0 mg/m2/day in the QOD schedule. The MTD was 107.5 mg/m2/day with QD and 210.7 mg/m2/day with QOD. QDx5 at the MTD in QD using a flat dose of 160 mg was evaluated. The most common adverse events in all regimens were gastrointestinal disorders and increased creatinine. DLTs were observed in 4 patients in QD (night blindness, visual disorder, AST/ ALT/gamma-GTP elevations, and anorexia) and in 2 patients in QOD (platelet count decreased, febrile neutropenia, pneumonia, respiratory failure, and septic shock). Reversible eye disorders were observed in all schedules, but those observed in QDx5 were limited to grade 1. The PK level demonstrated dose proportionality without unexpected accumulation under repeated administration. Dose-related HSP70 induction of PBMCs was observed. As of 20 September 2016, three confirmed durable PRs by RECIST were observed (239 days in GIST and 173 days in NSCLC with QD; 293 + days in NSCLC with QOD). PR and SD ≥ 12 weeks were observed in 15 out of 47 patients. Conclusions: TAS-116 had an acceptable safety profile under all schedules, especially QDx5. Preliminary antitumor activity was demonstrated with evidence of target engagement. Dose expansion at the MTD in this phase 1 study and the phase 2 study in patients with GIST are ongoing. Parts of this study will be expanded to the US with an amended study protocol. Clinical trial information: NCT02965885.
Axitinib plus crizotinib in patients with advanced solid tumors and metastatic renal cell carcinoma (mRCC): Preliminary phase 1b results.
Authors: Michaelson M Dror , Gupta Shilpa , Agarwal Neeraj , Szmulewitz Russell Zelig , Powles Thomas , Pili Roberto , Bruce Justine Yang , Vaishampayan Ulka N. , Larkin James M. G. , Rosbrook Brad , Lechuga Mariajose , Valota Olga , Tarazi Jamal Christo , Shepard Dale Randall 
Published: September 2018

2551 Background: Axitinib (AX) is a tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) and a standard treatment for mRCC. Upregulation of mesenchymal-epithelial transition factor (c-MET) is implicated in resistance to VEGFR-directed therapy. An ongoing ph Ib study (NCT01999972) evaluated the safety and efficacy of AX + crizotinib (CZ), a TKI of c-MET, anaplastic lymphoma kinase (ALK), and ROS1. Methods: mRCC patients (pts) with advanced solid tumors were treated with AX + CZ in a dose escalation phase (DESC). After determining maximum tolerated dose (MTD) (modified toxicity probability interval), mRCC pts were enrolled into 2 cohorts in a dose expansion phase (DEXP). Cohort 1 (C1) was treatment-naïve and C2 had 1–2 prior therapies. The primary objectives were to assess the tolerability of AX + CZ, to obtain the MTD, and to select the recommended phase II dose. Results: As of Aug 5, 2016, 24 pts were screened and 22 pts treated in the DESC. Pts received AX 3 mg twice daily (BID) + CZ 200 mg BID (n = 5); AX 3 mg BID + CZ 250 mg BID (n = 3); AX 5 mg BID + CZ 200 mg BID (n = 4); or AX 5 mg BID + CZ 250 mg BID (n = 10) in a median 4 (range 1–23) cycles. There were no cycle 1 dose-limiting toxicities. One pt discontinued due to an AX-related alanine aminotransferase increase. Fifteen (68.2%) pts experienced Grade 3–4 adverse events (AEs), none in ≥2 pts; 1 pt had a Grade 5 AE (disease progression). AX 5 mg BID + CZ 250 mg BID was established as the MTD. Most frequent AEs in the MTD group were fatigue (70.0%), nausea (70.0%) and diarrhea (60.0%). In the ongoing DEXP, 15 pts have been treated at the MTD (n = 11 in C1, and 4 C2). Response evaluation (RECIST) is ongoing, with 1 complete response (CR), 3 partial responses (PR) and 4 stable disease (SD) in 10 pts in C1, and 1 PR and 2 SD in 4 pts in C2. Overall, 10 (66.7%) pts experienced Grade 3–4 AEs and 1 pt had a Grade 5 AE (disease progression). Most frequent AEs (≥60% pts) were nausea and diarrhea. Conclusions: We have identified AX 5 mg BID + CZ 250 mg BID as the MTD for combination therapy. This regimen has manageable toxicities and exhibits antitumor activity in treatment-naïve and pretreated mRCC. Further studies in VEGFR, c-MET, ALK and ROS1 tumor types are warranted. Clinical trial information: NCT01999972.
Phase I study of indenoisoquinolines LMP776 in adults with relapsed solid tumors and lymphomas.
Authors: O'Sullivan Coyne Geraldine Helen , Kummar Shivaani , Meehan Robert S. , Streicher Howard , Takebe Naoko , Sharon Elad , Conley Barbara A. , Harris Lyndsay , Collins Jerry M. , Moore Nancy , Juwara Lamin , Rubinstein Larry , Quinn Mary Flanagan , Pommier Yves , Cushman Mark , Doroshow James H. , Chen Alice P. 
Published: September 2018

2558 Background: Indenoisoquinolines (ID) are non-camptothecin inhibitors of topoisomerase (TOP1) identified following a COMPARE analysis of the National Cancer Institute’s (NCI) in vitro anticancer drug discovery screen. IDs have improved characteristics over camptothecin top1 inhibitors, with better chemical stability (lacking the labile hydroxylactone E-ring) producing stable DNA breaks that are resistant to reversal of the trapped DNA-TOP1 cleavage complex and at different DNA sequence sites to camptothecins (Kohlhagen et al. Mol Pharmacol. 2005). IDs have shown more activity against camptothecin-resistant cell lines and mouse models, as well as in cells overexpressing the ATP-binding cassette (ABC) transporters, and multidrug resistance (MDR-1/ABCB1) genes. A parallel first-in-human Phase I study conducted at the NCI of LMP400 in patients with refractory solid tumors and lymphomas showed this molecule to be well tolerated (Kummar et al, Cancer Chemother Pharmacol. 2016). A trial of LMP776 (NSC725776), has completed accrual. Primary Objectives: define the maximum tolerated dose (MTD) of LMP776 and the dose-limiting toxicities (DLTs). Methods: Phase I trial using Design 4 of the Simon accelerated titration designs (Simon et al. JNCI, 1997), with doses escalated based on toxicity during cycle 1. LMP776 was administered via central line QD over 1 hour on days 1–5 q 28-days. Response is defined by RECIST 1.1 on CT. Results: 32 of 34 patients (pts) were evaluable for toxicity and response. Enrollment was expanded at dose level (DL) 2 to 6 pts due to a hypocalcemia DLT, with subsequent enrollment on a 3+3 design. MTD was established at DL7 (12mg/m2, DLT myelosuppression). Common Grade 3/4 adverse events by CTCAE v.4 included anemia (5 pts, 15%), thrombocytopenia (5), lymphopenia (5) and neutropenia (3 pts, 9%). 12 (37%) pts experienced stable disease (SD), with a median of 4 cycles of treatment (range 2-9). 10 (30%) pts with SD remained on study for ≥4 months, with 4 pts on study ≥6 months. Conclusions: LMP776 is overall well tolerated. Explorative correlatives and additional trials are being considered. Clinical trial information: NCT01051635.
A phase Ib/II clinical trial of a novel oxygen therapeutic in chemoradiation of glioblastoma.
Authors: Unger Evan C. , Lickliter Jason D. , Ruben Jeremy , Jennens Ross , Kichenadasse Ganessan , Gzell Cecelia , Mason Ralph , Carmody Raymond , Becker Jennifer , Zhou Heling , Sellenger Michael , Longacre Olivia , Graham Kaitlin , Stea Baldassarre 
Published: September 2018

2561 Background: Tumor hypoxia limits the response of glioblastoma multiforme (GBM) to radiotherapy (RT) and chemotherapy (temozolomide[TMZ]). Additionally, patient biomarkers are strong predictors of responsiveness to TMZ. The purpose of this study is to evaluate the use of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM and stratify the results based on predicted TMZ response. Methods: 11 adult GBM patients have been enrolled. Patients were administered DDFPe via IV infusion (2% w/vol at doses of 0.05, 0.1 or 0.17 mL/kg) an hour prior to each 2 Gy fraction of RT (30 fractions over 6-weeks) with supplemental oxygen. Patients also received standard concurrent and adjuvant TMZ. To confirm tumor re-oxygenation, patients underwent TOLD MRI before and after DDFPe administration. Archived tumor specimens were studied with GliomaSTRAT assay for methylated genes predictive of response. Patients were also studied with serial MRI scans per standard of care and followed for survival. Results: There were minimal acute adverse events related to DDFPe administration. One patient at each of dose levels 0.1 and 0.17 mL/kg developed symptomatic radiation necrosis, which was judged to be related to DDFPe. Enrollment has continued at the 0.1 mL/kg dose without additional significant DDFPe-related toxicity. TOLD MRI showed significant decrease in T1of tumor tissue consistent with tumor re-oxygenation (p=0.015) with no significant change in oxygenation of normal brain tissue. Historically, the average overall survival for GBM patients, for both TMZ responders and non-responders, is about 14.6 months. The progress chart for patient overall survival is listed below, 4 patients have died. All other patients are alive. Conclusions: DDFPe is a promising oxygen therapeutic for reversing tumor hypoxia. A Phase II study is being planned to assess its effectiveness. Clinical trial information: NCT02189109. [Table: see text]
A phase I study of the tolerability, safety, pharmacokinetics and preliminary antitumor effects of KBP-5209, a novel pan-HER inhibitor, in patients with advanced solid tumors.
Authors: Piha-Paul Sarina Anne , Sharma Sunil , Shih Chengkon , O'Neil Bert H. , Zhou Qinghong , Ding Yuli , Ou Na , Yu Tingting 
Published: September 2018

2565 Background: KBP-5209 is a novel potent and irreversible inhibitor of tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that preclinically has demonstrated potent antitumor activities in esophageal and gastric cancers and NSCLC. Methods: This first-in-human study (NCT02442414) was conducted to determine tolerability, safety, pharmacokinetics and antitumor activity of KBP-5209 administered QD or BID in patients (pts) with advanced solid tumors. Dose escalation (DE) initially was based on a modified accelerated titration plan and then shifted to a standard 3+3 design. The starting dose was 20 mg QD. Eligible patients were adults with advanced, refractory solid tumors with ECOG PS < 1. A cycle was 28 days. DLTs were evaluated for during the first cycle. DE enriched for patients with tumors having molecular alterations in EGFR or HER2/3. Dose escalation continues so dose expansion has not initiated. Results: As of 26 Nov, 2016, 23 pts (15 females, 8 males) are a part of the evaluable population with a median age 57 (37-79) treated at doses of 20mg (1), 40mg (3), 60mg (7), 70mg (4), 80mg (6) QD and 20mg BID (2).Tumor types included breast (6), CRC (4), ovarian (3), H&N (2), sarcoma (2), and NSCLC, sinus, gastric, gallbladder, pancreas, CUP tumor (1 each). Tumor genetic profiles were available for 20 pts. DLTs were G3 diarrhea, nausea, and vomiting, which occurred in 1 pt at 80mg QD and G3 Diarrhea, occurring in 1pt at 80mg QD. The most common adverse events related to study drug were diarrhea (60.9%), nausea (47.8%), vomiting (43.5%), fatigue (21.7%), decreased appetite (17.4%) and lipase increased (17.4%). Serious adverse events (SAEs) related to study drug were reported in 4pts: diarrhea (1 pt, 70mg QD; 1pt, 80mg QD), nausea and vomiting (1pt, 70mg QD), and diarrhea, nausea and vomiting (1 pt, 80mg QD). Stable disease has been observed in 7pts up to 24 weeks, in which 2/28 pts (7%) achieved tumor shrinkage. Conclusions: Based on the present data, KBP-5209 has been well tolerated with a safety profile similar to other pan-HER inhibitors. For QD dosing, maximum tolerated dose has been identified as 70mg QD. The BID dose escalation continues. Clinical trial information: NCT02442414.