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Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer. We did this randomised, open-label, phase 2/3 study at 202 academic medical centres in 24 countries. Patients with previously treated non-small-cell lung cancer with PD-L1 expression on at least 1% of tumour cells were randomly assigned (1:1:1) in blocks of six per stratum with an interactive voice-response system to receive pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The primary endpoints were overall survival and progression-free survival both in the total population and in patients with PD-L1 expression on at least 50% of tumour cells. We used a threshold for significance of p<0·00825 (one-sided) for the analysis of overall survival and a threshold of p<0·001 for progression-free survival. This trial is registered at ClinicalTrials.gov, number NCT01905657. Between Aug 28, 2013, and Feb 27, 2015, we enrolled 1034 patients: 345 allocated to pembrolizumab 2 mg/kg, 346 allocated to pembrolizumab 10 mg/kg, and 343 allocated to docetaxel. By Sept 30, 2015, 521 patients had died. In the total population, median overall survival was 10·4 months with pembrolizumab 2 mg/kg, 12·7 months with pembrolizumab 10 mg/kg, and 8·5 months with docetaxel. Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel (hazard ratio [HR] 0·71, 95% CI 0·58–0·88; p=0·0008) and for pembrolizumab 10 mg/kg versus docetaxel (0·61, 0·49–0·75; p<0·0001). Median progression-free survival was 3·9 months with pembrolizumab 2 mg/kg, 4·0 months with pembrolizumab 10 mg/kg, and 4·0 months with docetaxel, with no significant difference for pembrolizumab 2 mg/kg versus docetaxel (0·88, 0·74–1·05; p=0·07) or for pembrolizumab 10 mg/kg versus docetaxel (HR 0·79, 95% CI 0·66–0·94; p=0·004). Among patients with at least 50% of tumour cells expressing PD-L1, overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 14·9 months vs 8·2 months; HR 0·54, 95% CI 0·38–0·77; p=0·0002) and with pembrolizumab 10 mg/kg than with docetaxel (17·3 months vs 8·2 months; 0·50, 0·36–0·70; p<0·0001). Likewise, for this patient population, progression-free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 5·0 months vs 4·1 months; HR 0·59, 95% CI 0·44–0·78; p=0·0001) and with pembrolizumab 10 mg/kg than with docetaxel (5·2 months vs 4·1 months; 0·59, 0·45–0·78; p<0·0001). Grade 3–5 treatment-related adverse events were less common with pembrolizumab than with docetaxel (43 [13%] of 339 patients given 2 mg/kg, 55 [16%] of 343 given 10 mg/kg, and 109 [35%] of 309 given docetaxel). Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer. These data establish pembrolizumab as a new treatment option for this population and validate the use of PD-L1 selection. Merck & Co.

BackgroundDostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab.MethodsGARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500 mg every 3 weeks for 4 cycles, then dostarlimab 1000 mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review.ResultsScreening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5–22.1) for cohort A1 and 11.5 months (IQR 11.0–25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1–2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Grade≥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab.ConclusionDostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile.Trial registration numberNCT02715284.

ObjectiveThere is an increase in patient-reported outcome assessments to gain information on new drug candidates from the patient’s perspective. A data gap remains in patient-reported outcome measurements for anti-programmed death 1 (anti-PD-1) therapies in endometrial cancer. We present patient-reported outcome measures collected from patients with mismatch repair-deficient/microsatellite instability-high advanced or recurrent endometrial cancer treated with dostarlimab, an anti-PD-1 monoclonal antibody, in an expansion cohort of the GARNET trial.MethodsGARNET (NCT02715284) is a phase I single-arm study of dostarlimab monotherapy in multiple tumor types. Patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer were treated with 500 mg of intravenous dostarlimab once every 3 weeks for four cycles, then 1000 mg of intravenous dostarlimab every 6 weeks. Patient-reported outcome assessments were an exploratory endpoint, measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).ResultsAt data cut-off, 88 patients with mismatch repair-deficient endometrial cancer were included in the analysis. Patient-reported outcome assessment completion was >95.5% throughout cycle 7 of the trial, with no individual domain completion <90.9%. Quality of life, emotional functioning, and social functioning showed improvement compared with baseline. All symptom scores showed either improvement or stability from baseline through cycle 7. Categorical change in response across all symptom scales and single-item response scores showed stability or improvement for most patients. For patients who saw a worsening of their categorical change in response, ≤7.4% experienced a 2-category worsening and ≤2.5% experienced a 3-category worsening.ConclusionsMost patients remained stable or had improved quality of life while receiving dostarlimab for the treatment of recurrent or advanced mismatch repair-deficient endometrial cancer.Trial registration number NCT02715284.

Dinaciclib (SCH727965) is a selective CDKi chosen for clinical development based upon a favorable therapeutic index in cancer xenograft models. We performed a phase I dose escalation study of dinaciclib in relapsed and refractory chronic lymphocytic leukemia (CLL) patients with intact organ function and WBC<200 × 10 9  /l. Five separate dose levels (5 mg/m 2 , 7 mg/m 2 , 10 mg/m 2 , 14 mg/m 2 and 17 mg/m 2 ) were explored dosing on a weekly schedule × 3 with 1 week off (4-week cycles) using a standard 3+3 design with expansion cohorts to optimize safety. Fifty-two patients were enrolled with relapsed and refractory CLL. Escalation through cohorts occurred with two dose-limiting toxicity (DLTs) at the 17 mg/m 2 dose (tumor lysis syndrome (TLS) and pneumonia). The phase II expansion occurred at 14 mg/m 2 with 16 patients receiving this dose with one DLT (TLS). Additional stepped up dosing to the maximum tolerated dose was examined in 19 patients at this dose. Adverse events included cytopenias, transient laboratory abnormalities and TLS. Responses occurred in 28 (54%) of patients independent of del(17)(p13.1) with a median progression-free survival of 481 days. Dinaciclib is clinically active in relapsed CLL including those patients with high risk del(17)(p13.1) disease and warrants future study.

BackgroundImmune checkpoint inhibitors, like PD-1 or PD-L1 inhibitors, have changed the standard of care in multiple tumors, but durable responses have only been observed in a subset of patients. Overexpression of VEGF is frequently found in various tumors and plays critical roles in tumor angiogenesis and suppression of anti-tumor immune response. Bispecific antibodies targeting PD-(L)1 and VEGF have shown promising efficacy with a favorable safety profile in clinical trials. Specifically, ivonescimab, a cooperative PD-1 x VEGF bispecific antibody, demonstrated superiority to anti-PD-1 in randomized Phase 3 trial.1 2 CR-001 is a tetravalent bispecific antibody targeting PD-1 and VEGF. It consists of a bivalent, Fc-silenced anti-VEGF-A IgG1 antibody, with two anti-PD-1 single chain variable fragments fused to its C-terminus. Here, we report preclinical studies characterizing the cooperative pharmacology of CR-001 in vitro, anti-tumor activity in vivo, and single dose pharmacokinetic (PK) study in cynomolgus monkeys.MethodsThe antigen binding affinities of CR-001 with PD-1 and VEGF were measured by surface plasmon resonance. To evaluate the cooperative pharmacology in vitro, the binding activity of CR-001 to PD-1 was evaluated in PD-1 positive cells by flow cytometry in the presence of VEGF. The blockade of PD-1/PD-L1 signaling pathway was determined by NFAT luciferase reporter assay. SCID mice implanted with tumor cells were used to evaluate in vivo anti-tumor activity. The PK and receptor occupancy (RO) of CR-001 were evaluated in cynomolgus monkeys after a single intravenous administration.ResultsCR-001 bound with high affinity to human PD-1 and VEGF-A. In cell-based reporter assays, CR-001 inhibited PD-1/PD-L1 signaling and VEGF-A/VEGFR2 signaling with sub-nanomolar EC50 values. The PD-1 binding of CR-001 was increased in the presence of VEGF, leading to higher potency in PD-1/PD-L1 signaling blockade relative to CR-001 alone. Furthermore, CR-001 with VEGF showed increased IL-2 secretion compared to CR-001 alone in T cell activation assay using human PBMCs co-cultured with PD-L1 positive tumor cells. In vivo, CR-001 demonstrated potent anti-tumor activity, and was well-tolerated in cynomolgus monkeys after a single intravenous dose with peak PD-1 RO > 80%.ConclusionsCR-001 demonstrated cooperative pharmacology with increased binding to PD-1 in the presence of VEGF, augmenting PD-1/PD-L1 signaling blockade and enhancing T cell activation in vitro, consistent with preclinical evaluation of ivonescimab.1 In xenograft models, CR-001 demonstrated potent anti-tumor activity. CR-001 was well-tolerated in the cynomolgus monkey after a single dose. These data support clinical development of CR-001.ReferencesZhong, et al. Design of a fragment crystallizable-engineered tetravalent bispecific antibody targeting programmed cell death-1 and vascular endothelial growth factor with cooperative biological effects. iScience. 2025;28(3):111722.Xiong, et al. Ivonescimab versus pembrolizimab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomized, double-blind, phase 3 study in China. Lancet. 2025;405(10481):839–849.Ethics ApprovalAll animal protocols were reviewed and approved by the IACUC institution of the respective CROs. Further animals were housed, provided enrichment and monitored in accordance with the institution’s SOPs and protocols.

Introduction/BackgroundPROs enable direct measurement of the experiences of pts with cancer related to an intervention. Regulators increasingly use PROs to inform the risks and benefits of new drug candidates, focusing on 3 core concepts: physical functioning (PF), disease-related symptoms (DRS), and symptomatic adverse events (AEs).Dostarlimab is an investigational anti–programmed death-1 monoclonal antibody that has shown activity in pts with advanced dMMR EC (objective response rate, 42%; disease control rate, 58%) and an acceptable safety profile. Here, we report on PROs in pts treated with dostarlimab in the single-arm GARNET trial.MethodologyPts with recurrent or advanced dMMR/MSI-H EC that progressed on a platinum regimen received 500 mg Q3W*4 of dostarlimab, then 1000 mg Q6W until disease progression or discontinuation (DC). PRO assessment, an exploratory endpoint, was measured using the EORTC-QLQ-C30. PROs were collected at baseline (BL), each dose cycle, and after DC. For PF and DRS (pain and fatigue), we conducted multi-item descriptive analyses, including change from BL. For symptomatic AEs and tolerability (nausea, vomiting, constipation, diarrhoea, tiredness/fatigue), we conducted item-level analyses to understand response distribution and change in response categories from BL: improved, stable, and 1-, 2-, or 3-category worsening.ResultsPRO data were available for 66/104 pts who received ≥1 dose of dostarlimab. Questionnaire compliance was consistent across domains, ranging from 100% at BL to 45% at cycle 7. Pain, fatigue, and PF were maintained above BL starting at cycles 1, 3, and 4, respectively. Symptomatic AEs were experienced by a minority of pts, with <25% and <6% of pts having 1- or ≥2-category worsening, respectively. Improved scores were reported by 6% to 37% of pts.ConclusionsPROs from the GARNET trial showed that dostarlimab was generally well tolerated and disease-related symptoms were improved or maintained while on treatment. These data, along with the efficacy and safety profile of dostarlimab, support use of dostarlimab in pts with dMMR/MSI-H advanced EC.DisclosuresClinical trial registration: NCT02715284Funding: GlaxoSmithKline, Waltham, MA, USAEncore statement: This data is presented on behalf of the original authors with their permission. Presented at European Society for Medical Oncology (ESMO) annual meeting, September 19–21, 2020, Virtual.Dr. Kristeleit reports personal fees from Tesaro.Dr. Mathews reports institutional grants from Tesaro.Dr. Redondo reports institutional research funding from PharmaMar, Roche, and Eisai; and advisory roles at PharmaMar, AstraZeneca, Tesaro, Roche, and Eisai.Dr. Brown reports honoraria from Olympus; consulting or advisory role at Caris, Tesaro, Clovis, AstraZeneca, and Genentech; and speakers’ bureau at Clovis.Drs. Huang, Eliason, and Im are employees of GlaxoSmithKline.

PurposeNew immuno-oncology therapies targeting programmed cell death receptor 1 (PD-1) have improved patient outcomes in a broad range of cancers. The objective of this analysis was to evaluate the PK, pharmacodynamics (PDy), and safety of dostarlimab monotherapy in adult patients with previously-treated advanced solid tumors who participated in parts 1 and 2A of the phase 1 GARNET study.MethodsPart 1 featured a 3 + 3 weight-based dose–escalation study, in which 21 patients received dostarlimab 1, 3, or 10 mg/kg intravenously every 2 weeks. The 2 fixed-dose nonweight-based dosing regimens of dostarlimab 500 mg every 3 weeks (Q3W) and 1000 mg every 6 weeks (Q6W) were evaluated using a modified 6 + 6 design in part 2A (n = 13). In parts 1 and 2A, treatment with dostarlimab could continue for up to 2 years or until progression, unacceptable toxicity, patient withdrawal, investigator’s decision, or death.ResultsThe dostarlimab PK profile was dose proportional, and maximal achievable receptor occupancy (RO) was observed at all dose levels in the weight-based and fixed-dose cohorts. Trough dostarlimab concentration after administration of dostarlimab 500 mg Q3W was similar to that after dostarlimab 1000 mg Q6W, the values of which (≈40 µg/mL) projected well above the lowest dostarlimab concentration required for full peripheral RO. No dose-limiting toxicities were observed.ConclusionsDostarlimab demonstrated consistent and predictable PK and associated PDy. The observed safety profile was acceptable and characteristic of the anti-PD-1 drug class.Trial registration: ClinicalTrials.gov, NCT02715284. Registration date: March 9, 2016.

BackgroundCarboplatin-paclitaxel is standard systemic anticancer therapy for recurrent or advanced EC for which surgery and/or radiation are not curative. Dostarlimab (TSR-042) is an anti-programmed cell death (PD)-1 humanised monoclonal antibody that has demonstrated antitumour activity and an acceptable safety profile in patients (pts) with recurrent or advanced EC in the GARNET trial. The RUBY trial will evaluate the efficacy and safety of dostarlimab in combination with carboplatin-paclitaxel in recurrent or primary advanced EC compared with carboplatin-paclitaxel alone.Trial DesignThis is a global, randomised, double-blind, multicenter, placebo-controlled study. Eligible pts must have first recurrent or primary stage III or stage IV EC with a low potential for cure by radiation therapy or surgery alone or in combination. Pts with carcinosarcoma are eligible for enrolment. 470 pts will be enrolled from approximately 160 sites in the ENGOT countries, United States, and Canada. Stratification factors are DNA mismatch repair status (proficient [p], or deficient [d] MMR), prior external pelvic radiotherapy (yes or no), and disease status (recurrent, primary stage III or primary stage IV). Pts will be randomised 1:1 to receive combination dostarlimab 500 mg or placebo + carboplatin AUC 5 + paclitaxel 175 mg/m2 every 3 weeks for 6 cycles followed by dostarlimab 1000 mg or placebo monotherapy every 6 weeks for up to 3 years in the absence of progressive disease, death, unacceptable toxicity, or patient/physician decision to withdraw from the study. The primary endpoint is progression-free survival (PFS) as assessed by the investigator in the all-comers population and the dMMR population per RECIST version 1.1. Secondary efficacy endpoints are PFS assessed by blinded independent central review per RECIST version 1.1, overall survival, objective response rate, duration of response, disease control rate, safety and tolerability, and patient-reported outcomes.DisclosuresSponsor: GlaxoSmithKline, Waltham, MA, USANCT number: NCT03981796Encore statement: This data is presented on behalf of the original authors with their permission. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 29–31, 2020, Virtual.Dr. Mirza reports personal fees and other from Karyopharm Therapeutics; Personal fees and other from Sera Prognostics and Roche; Grants and Personal fees from AstraZeneca, Clovis Oncology, Pfizer, GSK, Genmab, BioCad, Sotio, Boehringer Ingelheim, Geneos Therapeutics, Merck, Oncology Venture, Seattle Genetics, Sera Prognostics,Takeda Pharmaceutical Company Ltd, and Zailab.Dr. Coleman reports consulting fees from Merck, Reoche/Genentech, AstraZeneca, Oncomed/Mateo, Novocure, Oncosec, Janssen, Clovis, Tesaro/GSK, Abbvie, Eisai, Arrivive, and Oncoquest; grants from Merck, Roche/Genentech, V-Foundation, AstraZeneca, Janssen, Clovis, Genmab and Abbvie; and honoraria/reimbursement from Merck, Roche/Genentech, AstraZeneca, Oncomed/Mateo, Novocure, Oncosec, Janssen, Clovis, Tesaro/GSK, Eisai, Arrivive and OncoQuest.Dr. Slomovitz reports consulting/advisory fees from GlaxoSmithKline.Dr. Powell reports consulting/advisory fees from Roche/Genentech, AstraZeneca, Tesaro, and Clovis Oncology; and speakers’ bureau at Genentech/Roche, AstraZeneca, Tesaro and Clovis Oncology.Drs. Hanker and Valabrega have nothing to disclose.Drs. Im, Walker, and Guo are employees of GlaxoSmithKline.

ObjectivesEndometrial (EC) and ovarian cancers (OC) are some of the leading causes of cancer death in women. Despite therapeutic advances, many patients eventually develop resistance to available standard of care (SOC) therapies. B7-H4 is a poor prognostic factor and is overexpressed in several cancers including endometrial, ovarian, and breast. As a member of the CD28/B7 family of cell surface proteins, it promotes tumorigenesis by suppressing anti-tumor immunity XMT-1660 is a B7-H4-targeted Dolasynthen ADC with a precise, optimized drug-to-antibody ratio and a DolaLock microtubule inhibitor payload with controlled bystander effect. In the preclinical setting, XMT-1660 has demonstrated anti-tumor activity in EC and OC PDX models.MethodsThe Ph1 trial includes a first-in-human dose escalation (DES) portion followed by a dose expansion (EXP) evaluating XMT-1660 in patients with EC, OC, and BC following progression on SOC. In the DES, BOIN design will be used to determine the MTD. The DES will assess safety and preliminary efficacy, and establish recommended phase 2 dose (RP2D). In the EXP portion, cohorts enrolling EC/OC, TNBC, ER+/HER2- BC, are planned and additional patients may be enrolled based on emerging data. The primary endpoints are safety and tolerability, overall response rate, disease control rate, and duration of response. Patients are not selected by B7-H4 status but baseline tumors samples are collected for retrospective analysis. The trial is currently enrolling patients. NCT05377996ResultsTrial in progressConclusionsTrial in progress

Introduction/BackgroundDostarlimab is a humanised programmed death (PD)-1 receptor monoclonal antibody that blocks interaction with the PD-1 ligands, PD-L1 and –L2. GARNET is a phase 1 study assessing antitumour activity and safety of dostarlimab monotherapy in patients with advanced solid tumours.MethodologyThis multicentre, open-label, single-arm study is being conducted in 2 parts, dose escalation and expansion. Here we report on 2 independent expansion cohorts of patients with recurrent or advanced endometrial cancer (EC) that progressed on or after a platinum-based chemotherapy regimen. Assignment to cohort A1 (mismatch mutation repair deficient [dMMR] EC) or cohort A2 (mismatch mutation repair proficient [MMRp] EC) was determined by immunohistochemistry (IHC) testing. Patients received 500 mg dostarlimab intravenously once every 3 weeks for 4 cycles, then 1000 mg once every 6 weeks until disease progression, discontinuation or withdrawal. The primary endpoints are objective response rate (ORR) and duration of response (DOR) by blinded independent central review using RECIST version 1.1.ResultsIn total, 126 dMMR and 145 MMRp pts identified by IHC were enrolled and dosed. Of these, 103 dMMR and 142 MMRp pts had measurable disease as baseline and sufficient follow-up time (6 months) for efficacy analyses, respectively. Patients that progressed prior to 6 months were included in the evaluable population. ORR for dMMR EC was 44.7%; ORR for MMRp EC was 13.4% (table 1). Median DOR and OS were not reached in either cohort. Overall, 15 pts (5.5%) discontinued treatment due a TRAE (5 dMMR, 10 MMRp). Safety by cohort and overall are shown in table 2. There were no deaths attributed to dostarlimab.Abstract 385 Table 1Antitumour activityAbstract 385 Table 2Most common adverse eventsConclusionDostarlimab demonstrated durable antitumour activity in both dMMR and MMRp advanced/recurrent EC. dMMR status by IHC was associated with a higher response rate. Dostarlimab demonstrated a notable disease control rate (35.2%; 2.1% complete response, 11.3% partial response, 21.8% stable disease) in patients with MMRp EC, which comprised a higher percentage of patients with Type II EC and is historically associated with a worse prognosis. No new safety signals were detected. These cohorts are the largest prospective evaluation of a PD-(L)1 therapy in EC to date.DisclosuresClinical trial registration: NCT02715284This study was sponsored by GlaxoSmithKline, Waltham, MA, USA.Dr. Oaknin reports consulting and honoraria from AstraZeneca, Tesaro, Clovis, PharmaMar, and Roche.Dr. Gilbert reports honoraria from Meck, AstraZeneca, and Pfizer.Dr. Tinker reports grants and personal fees from AstraZeneca.Dr. Sabatier reports grants from EISAI and AstraZeneca; personal fees from Roche, Pfizer, Tesaro, Novartis and AstraZeneca; and non-financial support from Roche, Pfizer, AstraZeneca, and Amgen.Dr. O’Malley reports personal fees from Immunogen, Eisai, Agenus, GSK : Consultant/Advisory Board for Clovis, Ambry, Abbvie, Janssen/J&J, Regeneron, Novacure, Myraid Genetics, Tarveda, Amgen, VentiRx, Array Biopharma, EMD Serono, Ergomed; Steering committee for Genentech/Roche and Merck; Institutional funding from Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, CERULEAN PHARMA, GOG Foundation, BMS, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., Inventiv Health Clinical, Iovance Biotherapeutics, Inc, and PRA International.Dr. Ghamande reports consulting fees from Seattle Genetics; speakers’ bureau fees from GSK; and institutional grants from GSK, Merck, Roche, Genentech, Takeda, Seattle Genetics, Advaxis, BMS, Clovis, Abbvie, and Tesaro.Dr. Pothuri reports grants, personal fees and non-financial support from GSK; Advisory Board fees from AstraZeneca and Clovis Oncology.Dr. Boni has nothing to disclose.Drs. Guo and Im are employees of GlaxoSmithKline.