A phase 1/2 study of intratumoral INT230-6 alone (IT-01) or in combination with pembrolizumab [KEYNOTE-A10] in adult subjects with locally advanced, unresectable and metastatic solid tumors refractory to therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2592-2592
Author(s):  
Anthony B. El-Khoueiry ◽  
Jacob Stephen Thomas ◽  
Anthony J. Olszanski ◽  
Nilofer Saba Azad ◽  
Giles Francis Whalen ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Tumor Regression ◽  
Phase 1 ◽  
Locally Advanced ◽  
Tumor Burden ◽  
Exploratory Analysis ◽  
Open Label ◽  
Open Label Phase ◽  
Grade 3 ◽  
Metastatic Sites

2592 Background: Study IT-01 (KEYNOTE-A10) evaluates INT230-6, a novel formulation of cisplatin (CIS) and vinblastine (VIN) with an amphiphilic cell penetration enhancer designed for intratumoral (IT) administration, alone or in combination with pembrolizumab (PEM), an antibody to PD-1. INT230-6 dosing is set by a tumor’s volume. In preclinical studies, INT230-6 increases drug dispersion throughout the tumor, allows drug diffusion into cancer cells and recruits dendritic, CD4 and CD8 T cells. The addition of PEM has been shown to improve these responses in models. Phase 1 data indicated INT230-6 alone induced tumor regression in both injected and non-injected lesions. Considering the large volume of drug injected and retained in the tumor, coupled with immune infiltration on biopsies, RECIST response methodology may not capture the benefit of INT230-6 treatment. Methods: IT-01 is an open-label phase 1/2 study, currently enrolling adult subjects with solid tumors in phase 2. INT230-6 was administered IT Q2W for 5 doses alone or with PEM 200mg Q3W. The study seeks to assess the safety and efficacy of IT INT230-6 alone and in combination with PEM. Results: 67 subjects have been enrolled (58 mono and 12 INT230-6 + PEM (3 started in mono, then received combo)) having a median of 3 prior therapies (0, 10). Median age was 60 (42, 85). 20+ cancer types were accrued; breast cancer and sarcoma were the most frequent. Over 500 image guided INT230-6 IT injections were given (253 to deep tumors) at doses of 0.3 to 172mL (86 mg CIS, 17.2 mg VIN) in a single session, which are higher amounts than typical IV doses. PK shows that 95% of INT230-6 active agents remain in the tumor. The most common (> 20%) related TEAEs for INT230-6 alone were localized pain (57%), nausea (36%), fatigue (29%) and vomiting (24%); with grade 3 TEAEs (> 1) of localized pain (5%) and anemia (3%). The safety in the combination was similar. There were no related grade 4 or 5 TEAEs. In evaluable monotherapy subjects (n = 43), the disease control rate (DCR) was 65% vs. 100% in PEM subjects (n = 5). Given the range of dose and entering tumor burden, an exploratory analysis of dose relative to tumor burden (TB) showed that subjects receiving a dose of INT230-6 < 50% of their reported TB (n = 30) had a mOS of 3.5 months. While in subjects receiving a dose of INT230-6 to ≥50% of TB (n = 37), mOS has not yet been reached after a median follow up of 9.5 months (HR: 0.26 (0.13,0.51)). Conclusions: INT230-6 is well tolerated when administered IT as monotherapy and combined with PEM. Given the challenge in assessing overall response rate following IT delivery, an exploratory analysis suggests prolonged survival for subjects receiving an INT230-6 dose ≥50% of their tumor burden compares favorably to the < 50% group and to literature accounting for prognostic factors (ECOG, LDH, # of metastatic sites). Clinical trial information: 03058289.

scholarly journals Surufatinib Plus Toripalimab in Patients with Advanced Solid Tumors: A Single-Arm, Open-Label, Phase 1 Trial

2020 ◽  
Author(s):  
Yanshuo Cao ◽  
Ming Lu ◽  
Yu Sun ◽  
Jifang Gong ◽  
Jie Li ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Phase 1 Trial ◽  
Open Label Phase ◽  
Grade 3

Abstract BackgroundPreclinical studies have supported a potential synergistic antitumor activity between surufatinib and anti-programed death ligand-1 (PD-L1). We describe here the results of a single-arm, open-label phase 1 trial to evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) in patients with advanced solid tumors treated with surufatinib combined with toripalimab, an inhibitor of PD-L1.MethodsThis is an open-label, dose escalation and expansion study in patients with solid tumors who had failed standard therapies or had no effective treatment. In the dose escalation stage, 3 cohorts of patients were treated with surufatinib, at dose levels of 200, 250, or 300 mg once daily (QD) in combination with a fixed dose of toripalimab 240 mg, every 3 weeks (Q3W), to evaluate maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Additional patients were enrolled in the dose expansion phase to further assess the efficacy, safety, and PK profile.ResultsFrom April 1, 2019 to July 10, 2020, 31 patients were screened, of which 28 patients were enrolled. One patient in the 300 mg cohort experienced dose limited toxicity (DLT), a grade 3 hyperthyroidism. The top 3 most common treatment-related adverse events of ≥ grade 3 were transaminases increased (17.9%), hypertension (14.3%) and blood bilirubin increased (10.7%). No treatment-related death or treatment discontinuation was identified. The RP2D was determined to be surufatinib 250 mg QD plus toripalimab 240 mg Q3W. Overall objective response rate was 22.2% [95% confidential interval (CI) 8.6‒42.3], and disease control rate reached 81.5% (95% CI 61.9‒93.7). ConclusionsSurufatinib plus toripalimab was well-tolerated, with no unexpected safety signals, and showed promising antitumor activity in patients with advanced solid tumors. Trial registrationclinicaltrials.gov, NCT03879057; Registered March 18, 2019, https://clinicaltrials.gov/ct2/show/NCT03879057

281 JAVELIN Medley VEGF: phase 2 study of avelumab + axitinib in patients with previously treated non-small cell lung cancer (NSCLC) or treatment naive, cisplatin-ineligible urothelial cancer (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A307-A307
Author(s):  
Gabriella Galffy ◽  
Iwona Lugowska ◽  
Elena Poddubskaya ◽  
Byoung Chul Cho ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Maintenance Treatment ◽  
Locally Advanced ◽  
Small Cell Lung ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Open Label Phase ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3

BackgroundAvelumab, a human anti–PD-L1 monoclonal antibody, has shown a manageable safety profile and antitumor activity in multiple tumor types, including platinum-resistant metastatic or recurrent NSCLC,1 and is approved for patients with locally advanced or metastatic UC who have progressed after ≥1 previous line of platinum-based chemotherapy2 3 and as maintenance treatment for those who have not progressed with platinum-based chemotherapy.4 JAVELIN Medley VEGF (NCT03472560) evaluated the efficacy and safety of avelumab + axitinib, a potent inhibitor of VEGFR 1, 2, and 3, in patients with advanced or metastatic NSCLC or UC.MethodsEligible patients with NSCLC had received ≥1 prior platinum-containing therapy and ≤2 prior lines of systemic therapy for locally advanced or metastatic disease; patients with UC were treatment naive in the locally advanced or metastatic setting and ineligible for cisplatin-containing chemotherapy. Patients were immune checkpoint inhibitor naïve and received avelumab 800 mg intravenously every 2 weeks + axitinib 5 mg orally twice daily. The primary endpoint was confirmed objective response (OR) per investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS) and safety. PD-L1 expression was assessed in baseline tumor samples (Ventana SP263 assay). Data have not undergone standard quality checks and are subject to change due to COVID-19–related healthcare burden.ResultsA total of 41 patients with NSCLC and 20 with UC received avelumab + axitinib. The confirmed OR rate was 31.7% (95% CI, 18.1–48.1) in the NSCLC cohort and 10% (95% CI, 1.2–31.7) in the UC cohort (all partial responses); 16 patients (39.0%) and 5 (25.0%) had stable disease, respectively. Responses were observed regardless of PD-L1 expression status. Median PFS was 5.5 months (95% CI, 2.5–7.0) in the NSCLC cohort and 2.3 months (95% CI, 1.8–5.6) in the UC cohort. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 24 patients (58.5%) in the NSCLC cohort; the most common was hypertension (n=7 [17.1%]). Grade ≥3 TRAEs occurred in 9 patients (45.0%) in the UC cohort; the most common were amylase increased, asthenia, decreased appetite, and palmar-plantar erythrodysesthesia syndrome (n=2 [10%] each). One patient in each cohort experienced a TRAE that led to death (gastric perforation and urinary bladder hemorrhage).ConclusionsAvelumab + axitinib showed antitumor activity and a manageable safety profile in patients with advanced or metastatic NSCLC or UC consistent with findings from studies of each drug alone and in combination.Trial RegistrationNCT03472560Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesGulley JL, Rajan A, Spigel DR, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 2017;18:599–610.Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 2018;19:51–64.Bavencio(avelumab) injection. [package insert] Darmstadt, Germany: Merck KGaA; 2019.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed August 19, 2020.

scholarly journals A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors

2021 ◽  
Author(s):  
Noboru Yamamoto ◽  
Toshio Shimizu ◽  
Kan Yonemori ◽  
Shigehisa Kitano ◽  
Shunsuke Kondo ◽  
...  
Keyword(s):  
Liver Function ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Enzyme Inhibitor ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Phase 1 Study ◽  
Open Label Phase

SummaryBackground This open-label, phase 1 study investigated TAS4464, a potent NEDD8-activating enzyme inhibitor, in patients with advanced/metastatic solid tumors (JapicCTI-173,488; registered 13/01/2017). The primary objective was dose-limiting toxicities (DLTs). Maximum-tolerated dose (MTD) was investigated using an accelerated titration design. Methods The starting 10-mg/m2 dose was followed by an initial accelerated stage (weekly dosing; n = 11). Based on liver function test (LFT) results, a 14-day, 20-mg/m2 dose lead-in period was implemented (weekly dosing with lead-in; n = 6). Results Abnormal LFT changes and gastrointestinal effects were the most common treatment-related adverse events (AEs). DLTs with 56-mg/m2 weekly dosing occurred in 1/5 patients; five patients had grade ≥ 2 abnormal LFT changes at 40- and 56-mg/m2 weekly doses. Further dose escalation ceased because of the possibility of severe abnormal LFT changes occurring. DLTs with weekly dosing with lead-in occurred in 1/5 patients at a 56-mg/m2 dose; MTD could not be determined because discontinuation criteria for additional enrollment at that particular dose level were met. As no further enrollment at lower doses occurred, dose escalation assessment was discontinued. Serious treatment-related AEs, AEs leading to treatment discontinuation, and DLTs were all related to abnormal LFT changes, suggesting that TAS4464 administration could affect liver function. This effect was dose-dependent but considered reversible. Complete or partial responses to TAS4464 were not observed; one patient achieved prolonged stable disease. Conclusions MTD could not be determined due to TAS4464 effects on liver function. Further evaluation of the mechanism of NEDD8-activating enzyme inhibitor-induced abnormal liver function is required. Trial registration number JapicCTI-173,488 (registered with Japan Pharmaceutical Information Center). Registration date 13 January 2017

A multicenter open-label phase 1 study evaluating the safety and tolerability of HMPL-306 in patients with locally advanced or metastatic solid tumors with IDH mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3159-TPS3159
Author(s):  
Filip Janku ◽  
John S. Kauh ◽  
Christopher Tucci ◽  
Zhao Yang ◽  
Marek K. Kania ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Tricarboxylic Acid Cycle ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Low Grade Glioma ◽  
Statistical Hypothesis ◽  
Low Grade ◽  
Open Label ◽  
Idh Mutations

TPS3159 Background: Isocitrate dehydrogenase (IDH) is a rate-limiting tricarboxylic acid cycle enzyme with 3 isoforms. Mutations in IDH1 and IDH2 result in gain-of-function activity that can cause tumor formation and/or progression and have been associated with various tumor types. Therefore, selective, single mutant IDH (mIDH) isotype inhibitors (mIDH1 or mIDH2) can lead to insufficient efficacy and the potential for tumor resistance. HMPL-306 is an innovative, small-molecule, orally available, highly selective, potent inhibitor of both mIDH1 and mIDH2. Clinical development of a compound that concurrently targets, inhibits, and suppresses multiple mIDHs could lead to significant and durable clinical benefit for patients (pts) with solid tumors harboring IDH mutations. Methods: This is a phase 1, open-label, dose escalation (Part 1) and dose expansion (Part 2) study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of HMPL-306 in pts ≥18 years with locally advanced or metastatic solid tumors with any IDH mutations. HMPL-306 will be administered orally, once daily in a 28-day continuous dosing treatment cycle. The HMPL-306 dose will be escalated in Part 1 according to the modified toxicity probability interval-2 (mTPI-2) design in 4 cohorts in approximately 15-20 pts: 50, 100, 150, and 200 mg. Eligible pts must have locally advanced or metastatic solid tumors with IDH1 or IDH2 mutations. The primary objectives are to evaluate safety, dose limiting toxicities (DLTs), tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and PK. Approximately 95 pts will be enrolled at the RP2D in Part 2 to further characterize the safety, tolerability, PK, PD, and preliminary anti-tumor activities of HMPL-306. Part 2 will include 5 dose expansion cohorts: cholangiocarcinoma (n = 20), skeletal chondrosarcoma (n = 20), low-grade glioma (n = 20), perioperative low-grade glioma (n = 15), any other solid tumor harboring an IDH1/2 mutation (n = 20). All pts will continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, or at the investigator’s discretion. Safety will be assessed based on reports of adverse events including clinical laboratory testing, vital signs, physical examinations, and electrocardiograms. All pts who receive any study treatment will be included in safety and efficacy analyses. Antitumor activity based on investigator-assessed overall response will be evaluated using descriptive analyses. Objective response rate will be calculated with 95% confidence interval using the Clopper-Pearson method. The Kaplan-Meier method will be used to summarize the time-to-event data such as progression-free survival and duration of response. No statistical hypothesis testing is planned. Enrollment started February 2021.

scholarly journals ACTR-59. A PHASE 1 STUDY OF BPM31510 PLUS VITAMIN K IN SUBJECTS WITH HIGH-GRADE GLIOMA THAT HAS RECURRED ON A BEVACIZUMAB-CONTAINING REGIMEN

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi27-vi27
Author(s):  
Lawrence Recht ◽  
Reena Thomas ◽  
Sophie Bertrand ◽  
Priya Yerballa ◽  
Gordon Li ◽  
...  
Keyword(s):  
Phase I ◽  
Vitamin K ◽  
Phase I Study ◽  
Phase 1 ◽  
High Grade Glioma ◽  
High Grade ◽  
Open Label ◽  
Open Label Phase ◽  
Grade 3

Abstract BACKGROUND High-grade gliomas (HGG) are characterized by dysregulated metabolism, utilizing glycolysis for energy production to support unrestricted growth. BPM 31510, an ubidecarenone (coenzyme Q10) containing lipid nanodispersion, causes a switch in cancer energy sourcing from glycolysis towards mitochondrial oxidative phosphorylation in vitro, reversing the Warburg effect and suggesting potential as an anti-tumor agent. The current study is a phase I study of BPM31510 + vitamin K in GB with tumor growth after bevacizumab (BEV). METHODS This is an open-label phase I study of BPM31510 continuous infusion with weekly vitamin K (10mg IM) in HGG patients using an mTPI design, starting at 110mg/kg, allowing for a single dose de-escalation and 2 dose-escalations. Patients had received first-line ChemoRadiation and were in recurrence following a BEV containing regimen. RESULTS 9 eligible and evaluable patients completed the 28 day DLT period. 8 patients had primary GB, 1 had anaplastic astrocytoma with confirmed pathologic transformation to GB. Median age was 55 years (27–67) and median KPS 70 (60–90) at enrollment. 4 patients were treated at the highest dose 171mg/kg, where there was a single DLT: Grade 3 AST & ALT. The most common grade 1–2 AEs possibly, probably or definitely related to drug were elevated AST, rash, and fatigue, each occurring in 3 patients. Median OS for 9 eligible/evaluable patients was 128 days (95% CI: 48–209) while PFS was 34 days (CI of mean 8.9). 3 patients are currently alive; 2 patients have survived >1 year. PK/PD data are being processed and will be presented. CONCLUSION This study confirms that BPM 31510 + vitamin K is safe and feasible in treatment-refractory HGG patients. Though this study demonstrates safety at 171mg/kg, the proposed dose for future studies in GB, based on additional pre-clinical and non-GB clinical data is 88mg/kg.

Epacadostat plus nivolumab in patients with advanced solid tumors: Preliminary phase I/II results of ECHO-204.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3003-3003 ◽  
Author(s):  
Raymond P. Perez ◽  
Matthew John Riese ◽  
Karl D. Lewis ◽  
Mansoor N. Saleh ◽  
Adil Daud ◽  
...  
Keyword(s):  
Phase 1 ◽  
Open Label ◽  
Common Grade ◽  
Open Label Phase ◽  
Study Population ◽  
N Dose ◽  
Grade 3 ◽  
Tumor Types ◽  
Preliminary Phase ◽  
Clinical Trial Information

3003 Background: ECHO-204 is an ongoing, open-label, phase 1/2 (P1/2) study of epacadostat (E; potent and selective oral inhibitor of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1) plus PD-1 inhibitor nivolumab (N) in patients (pts) with advanced cancers (NSCLC, MEL, OVC, CRC, SCCHN, B-cell NHL [including DLBCL], GBM). Preliminary P1/2 safety and tolerability outcomes for the overall study population and P2 response for select tumor types (SCCHN, MEL, OVC, CRC) are reported. Methods: In P1 dose escalation, pts received E (25, 50, 100, 300 mg BID) + N (3 mg/kg Q2W); in P2 cohort expansion, pts received E (100 or 300 mg BID) + N (240 mg Q2W). Safety/tolerability was assessed in pts receiving ≥1 E + N dose. Response was assessed in RECIST v1.1 evaluable pts; for recently enrolled pt subgroups, only preliminary DCR (CR+PR+SD) is presented. Results: As of 29OCT2016,241 pts (P1, n = 36; P2, n = 205) were enrolled. No DLT was observed in P1. Most common TRAEs (≥15%) in pts treated with E 100 mg (n = 70) and E 300 mg (n = 135) were rash (33% and 22%, respectively), fatigue (26% and 31%), and nausea (24% and 19%). Rash was the most common grade ≥3 TRAE in E 100 mg and E 300 mg subgroups (10% and 12%). TRAEs led to discontinuation in 7% (E 100 mg) and 13% (E 300 mg) of pts. There were no TR-deaths. For the 23 recently enrolled, efficacy-evaluable SCCHN pts treated with E 300 mg, preliminary DCR was 70% (n = 16). Of 30 MEL pts, 8 were treated with E 100 mg and 22 were more recently enrolled and treated with E 300 mg. ORR (CR+PR) and DCR in MEL pts treated with E 100 mg were 75% (n = 6; all PR) and 100% (n = 8; 2 SD), respectively. Preliminary DCR in MEL pts treated with E 300 mg was 64% (n = 14). Of 29 OVC pts, 18 were treated with E 100 mg and 11 with E 300 mg.ORR and DCR for OVC pts treated with E 100 mg were 11% (n = 2; 2 PR) and 28% (n = 5; 3 SD); for 11 OVC pts treated with E 300 mg, ORR and DCR were 18% (n = 2; 2 PR) and 36% (n = 4; 2 SD).For 25 CRC pts (all E 100 mg), ORR and DCR were 4% (n = 1; PR) and 24% (n = 6; 5 SD).Safety/efficacy evaluations are ongoing for all cohorts. Conclusions: E + N was generally well tolerated up to the maximum E 300-mg dose. P2 ORR/DCR outcomes are promising, particularly in SCCHN and MEL pts. Updated data will be presented at the meeting. Clinical trial information: NCT02327078.

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

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

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

Efficacy and safety of epacadostat plus pembrolizumab treatment of NSCLC: Preliminary phase I/II results of ECHO-202/KEYNOTE-037.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9014-9014 ◽  
Author(s):  
Tara C. Gangadhar ◽  
Bryan J. Schneider ◽  
Todd Michael Bauer ◽  
Jeffrey S. Wasser ◽  
Alexander I. Spira ◽  
...  
Keyword(s):  
Phase 1 ◽  
Phase 2 ◽  
Test Results ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase ◽  
History Of ◽  
Grade 3 ◽  
Preliminary Phase ◽  
Clinical Trial Information

9014 Background: ECHO-202/KEYNOTE-037 is an open-label, phase 1/2 study of epacadostat (a potent and selective oral inhibitor of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1) plus pembrolizumab (E + P) in patients (pts) with advanced tumors. We report preliminary efficacy and safety outcomes for the phase 1/2 NSCLC cohort. Methods: Adult pts with prior platinum-based therapy (tx) and no prior checkpoint inhibitor tx were eligible. Phase 1 dose-escalation tx was E (25, 50, 100, 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) tx doses were selected for phase 2 cohort expansion. Efficacy was evaluated by tumor proportion score (TPS [% viable tumor cells, PD-L1 staining]: < 50% and ≥50%) and by prior lines of tx in RECIST 1.1 evaluable pts. Safety was assessed in pts receiving ≥1 E + P dose. Results: As of 29OCT2016,43 pts (phase 1, n = 12; phase 2, n = 31) were evaluated. Median age was 65 years, 58% of pts were women, 12% were EGFR-positive, and 23% were KRAS-positive. Most pts had a history of smoking (84%), ≤2 prior lines of tx (84%), and no prior TKI tx (93%). For the 40 efficacy-evaluable pts, ORR (CR+PR) and DCR (CR+PR+SD) were 35% (14/40; 14 PR) and 60% (24/40; 10 SD), respectively. PD-L1 TPS test results were available in 28/40 efficacy-evaluable pts. ORR and DCR for pts with TPS ≥50% and ≤2 prior tx were 43% (3/7; all PR) and 57% (4/7; 1 SD), respectively; for pts with TPS < 50% and ≤2 prior tx, ORR and DCR were 35% (6/17; all PR) and 53% (9/17; 3 SD). Among the 40 efficacy-evaluable pts, 12/14 responses were ongoing (range, 1+ to 519 days) at data cutoff. PFS and biomarker analyses are ongoing. Across all 43 pts, most frequent TRAEs were fatigue (19%), arthralgia (9%), and increased AST (9%); 16% of pts had grade ≥3 TRAEs, and increased lipase (asymptomatic) was the only grade ≥3 TRAE that occurred in > 1 pt (n = 2). Two pts discontinued due to TRAEs (grade 3 increased AST, grade 2 increased ALT [n = 1]; grade 2 brain edema [n = 1]). Conclusions: E + P was generally well tolerated and associated with promising responses in pts with NSCLC. A phase 3 NSCLC study is planned. Clinical trial information: NCT02178722.

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