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Immune checkpoint inhibitors have revolutionized care for many cancer indications, with considerable effort now being focused on increasing the rate, depth, and duration of patient response. One strategy is to combine immune strategies (for example, ctla-4 and PD-1/L1-directed agents) to harness additive or synergistic efficacy while minimizing toxicity. Despite encouraging results with such combinations in multiple tumour types, numerous clinical challenges remain, including a lack of biomarkers that reliably predict outcome, the emergence of therapeutic resistance, and optimal management of immune-related toxicities. Furthermore, the selection of ideal combinations from the myriad of immune, systemic, and locoregional therapies has yet to be determined. A longitudinal network-based approach could offer advantages in addressing those critical questions, including long-term follow-up of patients beyond individual trials. The molecular cancer registry Personalize My Treatment, managed by the Networks of Centres of Excellence nonprofit organization Exactis Innovation, is uniquely positioned to accelerate Canadian immuno-oncology (io) research efforts throughout its national network of cancer sites. To gain deeper insight into how a pan-Canadian network could advance research in io combinations, Exactis invited preeminent clinical and scientific advisors from across Canada to a roundtable event in November 2017. The present white paper captures the expert advice provided: leverage longitudinal patient data collection; facilitate network collaboration and assay harmonization; synergize with existing initiatives, networks, and biobanks; and develop an io combination trial based on Canadian discoveries. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the articles about the explosion of nuclear device in China.

Background: With cryoablation, probes are inserted into tumors to induce crystallization, osmotic changes, vascular stasis, and ultimately tumor necrosis. The resultant release of tumor antigens could activate a tumor-specific immune response through antigen presentation by dendritic cells (DC) to T-cells. Cryoablation is an effective treatment modality in many cancers (Habash 2007), and feasibility studies have shown that thermal ablation can be performed safely and effectively in small breast cancers (Noguchi 2007). To amplify immune response, we use ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T lymphocyte antigen-4 (CTLA4), a co-inhibitory molecule present on the surface of activated T cells. Durable and clinically significant responses to ipilimumab have been reported in prostate, bladder, and renal cell cancers. Ipilimumab has been most extensively studied in malignant melanoma, with 10-20% response rates and significant survival benefits reported (Wolchok 2010, Hodi 2010). Cryoablation-mediated tumor destruction exposes DCs to sufficient quantities of tumor antigens and inflammatory cytokines to induce DC maturation and activation. Furthermore, in preclinical murine models, the combination of cryoablation with CTLA4 blockade successfully mediates rejection of metastatic prostate cancer lesions and prevents growth of secondary tumors (Waitz 2012). Combined ablative therapy with CTLA4 blockade is appealing due to the relative safety of percutaneous ablation in early stage breast cancer and the efficacy and tolerability of ipilimumab administration in numerous settings. We therefore hypothesize that this strategy could confer long-term immunity, and ultimately cure, for women with early stage breast cancer. In this pilot study, the safety and tolerability of pre-operative cryoablation alone, single dose ipilimumab (10mg/kg) alone, or the combination is being evaluated in women with early stage breast cancer. Design: Three sequential test groups of 6 patients are being enrolled (total N=18). The study groups are: pre-operative cryoablation alone (A), pre-operative single dose ipilimumab alone Eligibility: Eligible women are age 18y with early-stage, operable, 1.5 cm invasive breast cancer, no history of autoimmune disease and planning mastectomy. (B), and pre-operative single-dose ipilimumab followed by cryoablation (C). Groups A and B must meet the safety primary endpoint before enrollment to study arm C is begun. The timing of all study interventions is defined by the pre-determined, non-study surgery date. Primary aim: To determine the safety and tolerability of pre-operative ipilimumab and/or cryoablation in patients with resectable breast cancer. Secondary aims: To explore and characterize pre- and post-intervention radiographic and immunological (peripheral blood and tumor tissue) correlates. Statistics: If at least 5 of the 6 patients in each group proceed with surgery without delay, the regimen will be considered safe/tolerable for further study. Secondary aims are exploratory. Eligibility: Eligible women are age ≥18y with early-stage, operable, ≥1.5 cm invasive breast cancer, no history of autoimmune disease and planning mastectomy. Study Status: As of June 12, 2012, Study Arm A is filled: 4 women have undergone cryoablation and mastectomy and 2 have undergone cryoablation and are awaiting surgery. [ABSTRACT FROM AUTHOR]

Background: Src kinase plays an important role in proliferation, survival, angiogenesis and metastasis in several malignancies including breast cancer. Therefore, inhibition of Src and other tyrosine kinases (TKs) represents a novel therapeutic approach. Dasatinib is a potent inhibitor of 5 oncogenic TKs, inhibits VEGF-stimulated proliferation, has potent bone anti-resorptive activity and selectively inhibits basal-type breast cancer growth. Preclinically, the combination of dasatinib and paclitaxel had superior antitumor activity to either agent alone. In a previous phase I study, we determined that, in combination with weekly paclitaxel, the optimum dose of dasatinib was 120mg. Of note, 4/9 (44%) patients treated at or above this dasatinib dose level had objective tumor response. We now present results from the phase II trial of this combination. Methods: Patients with MBC, ECOG PS 0-1, normal hepatic, renal, marrow function were eligible. Patients had measurable, HER2-negative metastatic breast cancer (MBC), ≤2 prior therapies for MBC. Treatment consisted of weekly paclitaxel 80 mg/m² IV 3/4 weeks + Dasatinib 120mg orally daily. Response was assessed by RECIST after every 8 weeks of therapy. Simon's two-stage optimal design was used to test the null hypothesis of a 15% response rate (RR) against the alternative of a 30% RR. In stage I, planned enrollment was 23 patients based on Type I and Type II errors of 10%. If 4 or more responses are observed, enrollment will be extended to 55 patients. Exploratory correlative biomarkers of clinical benefit include Src phosphorylation (p-Src) in peripheral blood mononuclear cells, plasma levels of VEGFR2 and collagen Type IV, circulating tumor cells (CTCs) and tumor gene expression profiling. Results: 21 patients (19 females, 2 male) have enrolled; median age 48 (range 30-79). Patients received a median of 1 prior therapy for MBC (range 0-2). 6 patients are not assessable for response: 1 has received <8 weeks treatment, 5 came off study for toxicity (2 hypersensitivity reaction to paclitaxel, 1 infection, 1 diarrhea/nausea, 1 bleeding likely related to anticoagulation). Among the 15 patients assessable for response, best response to date is as follows: 2 (13%) patients partial response, 11 (73%) patients stable disease (SD) and 2 (13%) patients progression of disease. Of patients with SD, 6/11 (55%) continue on treatment after median of 2 months (range 2-10) and 5/11 (45%) patients have come off study after median of 10 months (range 3-21). Most toxicities have been hematological and low grade. Diarrhea and neuropathy have generally been low grade and no new toxicities related to the combination have occurred since expansion into the phase II. Potential biomarkers of clinical benefit including, p-Src, VEGFR2, collagen Type IV, and CTCs will be presented. Conclusion: Data from this phase II has demonstrated preliminary evidence of activity for weekly paclitaxel and dasatinib 120mg in patients with MBC. These findings are consistent with data from this dose level in the earlier phase I study. Predictive biomarkers of clinical benefit are under investigation. [ABSTRACT FROM AUTHOR]

Background: The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) is standard of care for the treatment of early triple-negative breast cancer (TNBC) after KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates with the combination. However, the optimal treatment strategy for TNBC remains uncertain as questions persist about which patients benefit from pembro and the best treatment schedule and regimen. We identified real-world clinical characteristics and treatment variables associated with response to NAC plus pembro., Methods: Patients with early TNBC treated with NAC plus pembro between February 2020 and September 2023 were identified. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. Cox proportional hazard prediction models were used to identify predictors of invasive disease-free survival and overall survival in this cohort., Results: A pCR was achieved in 75 (63.6%) of 118 patients. Age at diagnosis (P = .04), Ki-67 (P = .004), duration from start of pembro to surgery (P = .006) and NAC to surgery (P = .01), number of cycles of pembro (P = .04) and NAC (P = .02), and completion of at least 8 cycles of pembro (P = .015) and NAC (P = .015) were each significantly associated with pCR in univariate analysis. In multivariate analysis, patients younger than 55 years at time of diagnosis (vs age > 55 years) and those completing at least 8 cycles of pembro remained predictive of pCR (OR's 2.50, 2.49, P = .035 and .037, respectively)., Conclusions: In this real-world analysis of patients with TNBC treated with NAC plus pembro, younger age and the completion of at least 8 cycles of pembrolizumab were associated with pCR., (© The Author(s) 2024. Published by Oxford University Press.)

Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer., Competing Interests: Declaration of interests H.L.M. has received consulting fees from Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Immunomedics, Merck, OBI Pharma, Pfizer, Puma, Spectrum Pharmaceuticals, Syndax Pharmaceuticals, Peregrine, Calithera, Daiichi-Sankyo, Seattle Genetics, AstraZeneca, Gilead, Crown Bioscience, and TapImmune. H.L.M. has received research support from Bristol-Myers Squibb; MedImmune, LLC/AstraZeneca; BTG; and Merck. R.B. has received research support (to the institution) from Genentech, AstraZeneca, Merck, Takeda, Eli Lilly, Pfizer, and Seattle Genetics, has received consulting fees from Pfizer, AstraZeneca, Seattle Genetics, and Gilead, and has received compensation to serve as a speaker/panelist for MJH Healthcare, Eli Lilly, and Curio Science. S.L.S. has received project-based research funding from Merck outside of the submitted work. S.R.V.K. is a founder and consultant at Faeth Therapeutics and Transomic Technologies. None of these disclosures are related to this work. No other potential disclosures are reported by any of the authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: In the phase 3 KEYNOTE-522 study, addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab significantly increased pathologic complete response (pCR) and event-free survival (EFS) vs neoadjuvant chemotherapy in patients with early triple-negative breast cancer., Objective: To evaluate efficacy and safety outcomes for patients enrolled in East/Southeast Asia (Asia) in KEYNOTE-522., Design, Setting, and Participants: KEYNOTE-522, a multicenter, double-blind, randomized clinical trial, enrolled 1174 patients between March 7, 2017, and September 13, 2018. For interim EFS and overall survival (OS) analyses (data cutoff, March 23, 2021), median follow-up was 39.8 months (range, 30.4-46.9 months) for pembrolizumab plus chemotherapy and 40.8 months (range, 30.1-46.9 months) for placebo plus chemotherapy. Data cutoff for pCR analysis was September 24, 2018. This secondary analysis included adults enrolled in Asia with newly diagnosed, previously untreated, nonmetastatic triple-negative breast cancer (tumor stage T1c and nodal stage N1-2 or tumor stage T2-4 and nodal stage N0-2) and Eastern Cooperative Oncology Group performance status of 0 to 1, regardless of programmed cell death ligand 1 (PD-L1) status., Intervention: Patients were randomized 2:1 to 4 cycles of pembrolizumab (200 mg every 3 weeks) or placebo plus carboplatin and paclitaxel and another 4 cycles of pembrolizumab or placebo plus doxorubicin or epirubicin and cyclophosphamide before surgery. After definitive surgery, patients received pembrolizumab or placebo every 3 weeks for 9 cycles or until recurrence or unacceptable toxic effects., Main Outcomes and Measures: The main outcome was pCR (no evidence of primary tumor after neoadjuvant therapy or carcinoma in situ after neoadjuvant therapy and no regional lymph node involvement after neoadjuvant therapy) at the time of definitive surgery and EFS., Results: A total of 216 of 1174 randomized patients (all female; median [range] age, 46.0 [24.0-71.0] years) were from Korea, Japan, Taiwan, and Singapore (136 in the pembrolizumab plus chemotherapy group and 80 in the placebo plus chemotherapy group). Of these patients, 104 (76.5%) in the pembrolizumab plus chemotherapy group and 60 (75.0%) in the placebo plus chemotherapy group had a tumor PD-L1 combined positive score of 1 or greater. Pathologic complete response was 58.7% (95% CI, 46.7%-69.9%) with pembrolizumab plus chemotherapy and 40.0% (95% CI, 26.4%-54.8%) with placebo plus chemotherapy; benefit was observed regardless of PD-L1 status. Thirteen patients (9.6%) in the pembrolizumab plus chemotherapy group and 20 patients (25.0%) in the placebo plus chemotherapy group had EFS events (hazard ratio, 0.35; 95% CI, 0.17-0.71). The 36-month EFS rate was 91.2% (95% CI, 85.0%-94.9%) with pembrolizumab plus chemotherapy and 77.2% (95% CI, 66.3%-85.0%) with placebo plus chemotherapy. Grade 3 to 4 treatment-related adverse events occurred in 109 patients (80.1%) receiving pembrolizumab plus chemotherapy and 64 patients (81.0%) receiving placebo plus chemotherapy., Conclusions and Relevance: In this subgroup analysis of patients enrolled in Asia in KEYNOTE-522, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab led to clinically meaningful improvements in pCR and EFS vs neoadjuvant chemotherapy alone. These findings support the use of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab as a standard-of-care therapy for patients in Asian countries with early triple-negative breast cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT03036488.

NDP52 is an autophagy receptor involved in the recognition and degradation of invading pathogens and damaged organelles. Although NDP52 was first identified in the nucleus and is expressed throughout the cell, to date, there is no clear nuclear functions for NDP52. Here, we use a multidisciplinary approach to characterise the biochemical properties and nuclear roles of NDP52. We find that NDP52 clusters with RNA Polymerase II (RNAPII) at transcription initiation sites and that its overexpression promotes the formation of additional transcriptional clusters. We also show that depletion of NDP52 impacts overall gene expression levels in two model mammalian cells, and that transcription inhibition affects the spatial organisation and molecular dynamics of NDP52 in the nucleus. This directly links NDP52 to a role in RNAPII-dependent transcription. Furthermore, we also show that NDP52 binds specifically and with high affinity to double-stranded DNA (dsDNA) and that this interaction leads to changes in DNA structure in vitro. This, together with our proteomics data indicating enrichment for interactions with nucleosome remodelling proteins and DNA structure regulators, suggests a possible function for NDP52 in chromatin regulation. Overall, here we uncover nuclear roles for NDP52 in gene expression and DNA structure regulation., (© 2023. The Author(s).)

Background: Evidence to date supports continued human epidermal growth factor receptor 2 (HER2) suppression beyond progression on HER2-directed therapy for advanced HER2-positive breast cancer. Data from several phase II and III trials evaluating HER2-directed therapy following second-line T-DM1 have recently become available., Methods: We performed a systematic search of the published and presented literature to identify phase II and phase III trials assessing novel HER2-targeted agents as third-line therapy or beyond for HER2-positive advanced breast cancer using search terms 'breast cancer' AND 'HER2' AND 'advanced' AND ('phase II' OR 'phase III')., Results: Eight clinical trials reporting efficacy outcomes on third-line or greater HER2-directed therapy for HER2-positive advanced breast cancer were identified. In phase III trials, margetuximab and neratinib combinations demonstrated significant 1.3-month (hazard ratio, HR = 0.71, p  < 0.001) and 0.1-month (HR = 0.76, p  = 0.006) net improvements in median progression-free survival (PFS), respectively, with no significant improvements in overall survival (OS). Tucatinib added to trastuzumab and capecitabine demonstrated a significant 2.7-month improvement in median PFS (HR = 0.57, p  < 0.00001) and a 5.5-month improvement in median OS (HR = 0.73, p  = 0.004) in a randomized phase II trial, including significant clinical benefit for patients with brain metastases. Finally, trastuzumab-deruxtecan, zenocutuzumab, and poziotinib demonstrated benefit in phase II trials with the most robust overall response rate (62.0%) and median duration of response (18.2 months) observed for trastuzumab-deruxtecan among heavily pretreated patients., Conclusion: Tucatinib plus trastuzumab and capecitabine significantly prolongs OS, and promising preliminary response outcomes for trastuzumab-deruxtecan suggest that sequencing of these regimens following second-line therapy is reasonable., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Christine Simmons has served in a consultancy or advisory role and received honorarium from Pfizer, Eli Lilly, Roche, and Mylan, and has received research funding from AstraZeneca Global, Roche, Knight Therapeutics, Viatris, and Pfizer. Daniel Rayson has served in a consultancy or advisory role and received honorarium from AstraZeneca, Pfizer, Eli Lilly, Merck, Gilead, Novartis, and Seagen. Anil Abraham Joy has served in a consultancy or advisory role and received honorarium from AstraZeneca, BMS, Eli Lilly, Knight Therapeutics, Gilead, Roche, Novartis, Pfizer, Mylan, and Teva. Jan-Willem Henning has served in a consultancy or advisory role and received honorarium from AstraZeneca, Pfizer, Novartis, Eli Lilly, Roche, Knight Therapeutics, Seagen, and Mylan. Julie Lemieux has served in a consultancy or advisory role and received honorarium from Novartis, Eli Lilly, Gilead, Pfizer, and AstraZeneca, and has received research funding from Celgene, Genentech, GlaxoSmithKline, Roche, Millennium, Novartis, Merck Gilead, Abbvie, Acerta, Bayer, Pfizer, BMS, Esai, Sanofi, Janssen, Ozmosys, Sierra Astrazeneca, and Takeda. Heather McArthur has served in a consultancy or advisory role and received honorarium from Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Puma Biotechnology, Daiichi-Sankyo, Seattle Genetics, Merck, and Lilly, and has received research funding from Bristol-Myers Squibb, MedImmune, LLC/AstraZenica, BTG, and Merck. Paul B. Card has nothing to declare. Rebecca Dent has served in a consultancy or advisory role and received honorarium from AstraZeneca, Viatris, Pfizer, Eisai, Merck, Eli Lilly, Novartis, and Roche, and has received research funding from AstraZeneca. Christine Brezden-Masley has served in a consultancy or advisory role and received honorarium from AstraZeneca, Eli Lilly, Knight Therapeutics, Mylan, Gilead, Roche, Amgen, Seagen, and Novartis, and has received research funding from Eli Lilly and AstraZeneca., (© The Author(s), 2022.)

Metaplastic breast cancer is a rare and often chemo-refractory subtype of breast cancer with poor prognosis and limited treatment options. Recent studies have reported overexpression of programmed death ligand 1 (PD-L1) in metaplastic breast cancers, and there are several reports of anti-PD-1/L1 being potentially active in this disease. In this case series, we present 5 patients with metastatic metaplastic breast cancer treated with anti-PD-1-based therapy at a single center, with 3 of 5 cases demonstrating a response to therapy, and one of the responding cases being a metaplastic lobular carcinoma with low-level hormone receptor expression. Cases were evaluated for PD-L1 expression, tumor infiltrating lymphocytes (TILs), DNA mutations, RNA sequencing, and T-cell receptor sequencing. Duration of the response in these cases was limited, in contrast to the more durable responses noted in other recently published reports., Competing Interests: WR: Research support from Galectin Therapeutics, Bristol Myers Squibb (BMS), Merck, Tesaro/GlaxoSmithKline, MiNA Therapeutics, Inhibrx, Veana Therapeutics, Aeglea Biotherapeutics, Shimadzu, OncoSec, and Calibr. Patents/Royalties: Galectin Therapeutics. Advisory Boards: Nektar Therapeutics, Vesselon. DP: Received advisory board honoraria and institutional research funding support from Brooklyn ImmunoTherapeutics, Bristol-Myers Squibb, and Merck Laboratories. DP receives speaker bureau honoraria from Genentech and Novartis. Unrelated to this work, DP has received additional advisory board honoraria from other entities. RB: Consulting fees: Genomic Health, Astra Zeneca, Genentech; Institutional research funding: Seattle Genetics, Ichnos Biosciences, Merck; Honoraria for speakers bureau: Genentech, Seattle Genetics. HM: Consulting or Advisory Role - AstraZeneca; Bristol-Myers Squibb; Daiichi Sankyo; Genentech; Genomic Health; Immunomedics; Lilly; Merck; Pfizer; Puma Biotechnology; Puma Biotechnology; Seattle Genetics, Research Funding - Bristol-Myers Squibb (Inst); Lilly (Inst); Merck, (Inst); ZIOPHARM Oncology (Inst), Travel, Accommodations, Expenses - Amgen; AstraZeneca; Bristol-Myers Squibb; DAVA Pharmaceuticals; Genentech; Immunomedics; Lilly; Merck; Pfizer; Puma Biotechnology; Spectrum Pharmaceuticals, Other Relationship - Genomic Health; Lilly. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Rajamanickam, Bernard, Chun, Wu, Martel, Sun, Redmond, Sanchez, Basho, McArthur and Page.)

Historically, breast cancer tumors have been considered immunologically quiescent, with the majority of tumors demonstrating low lymphocyte infiltration, low mutational burden, and modest objective response rates to anti-PD-1/PD-L1 monotherapy. Tumor and immunologic profiling has shed light on potential mechanisms of immune evasion in breast cancer, as well as unique aspects of the tumor microenvironment (TME). These include elements associated with antigen processing and presentation as well as immunosuppressive elements, which may be targeted therapeutically. Examples of such therapeutic strategies include efforts to (1) expand effector T-cells, natural killer (NK) cells and immunostimulatory dendritic cells (DCs), (2) improve antigen presentation, and (3) decrease inhibitory cytokines, tumor-associated M2 macrophages, regulatory T- and B-cells and myeloid derived suppressor cells (MDSCs). The goal of these approaches is to alter the TME, thereby making breast tumors more responsive to immunotherapy. In this review, we summarize key developments in our understanding of antitumor immunity in breast cancer, as well as emerging therapeutic modalities that may leverage that understanding to overcome immunologic resistance., Competing Interests: Competing interestsGatti-Mays: No COI or disclosures. Balko: Receives research support from Genentech/Roche, Bristol Myers Squibb, and Incyte Corporation, has received consulting/expert witness fees from Novartis, and is an inventor on provisional patents regarding immunotherapy targets and biomarkers in cancer. Gameiro: No COIs or disclosures. Bear: Receives research support from Merck and serves on the Advisory Board for Merck. Prabhakaran: No COI or disclosures. Fukui: No COI or disclosures. Disis: COI: grants from Epithany, Celgene, EMD Serono, Pfizer, Seattle Genetics, Silverback Therapeutics, Janssen. Stockholder in Epithany. Nanda: Advisory Board: AstraZeneca, Athenex, Celgene, Daiichi Sankyo, Inc, Genentech, MacroGenics, Merck, Novartis, Pfizer, Puma, Syndax. DSMB:G1 Therapeutics Research Funding: AstraZeneca, Celgene, Corcept. Therapeutics, Genentech/Roche, Immunomedics, Merck, Odonate Therapeutics, Pfizer, Seattle Genetics, Gulley: National Cancer Institutes has several Cooperative Research and Development Agreements (CRADAs) with various biotech and pharma agencies involved in immunotherapy. Kalinsky: Consulting: Biotheranostics, Eli-Lilly, Pfizer, Amgen, Novartis, Eisai, AstraZeneca, Odonate Therapeutics, Ipsen, Genentech. Speakers’ bureau: Eli-Lilly. Institutional support: Incyte, Genentech, Eli-Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zeno Pharmaceuticals, CytomX Therapeutics. Spouse: employment at Array Biopharma Vendor-sponsored travel: Eli-Lilly, Novartis, Genentech, Ipsen and Amgen. Abdul Sater: No COI or disclosures. Sprano: Receives research support: Deciphera, Inc., Prescient Therapeutics; Paid consultant: Astra Zeneca, Pfizer; Pharmaceutical sponsored research: Genentech. Cescon: Honoraria (non-accredited CME) Pfizer, and Novartis. Consulting or advisory role: Pfizer, AstraZeneca, Novartis, GlaxoSmithKline, Merck, Roche/Genentech, Agendia, Puma Biotechnology and Dynamo Therapeutics. Research funding (to instituton): Merck, Roche/Genentech, GlaxoSmithKline, and Pfizer. Page: Research support: BMS, Merck, Brooklyn ImmunoTherapeutics. Speakers Bureau: Genentech, Novartis. Scientific Advisory Board: BMS, Merck, Syndax, Nektar, Puma, Nanostring. McArthur: Consulting: Merck, Spectrum Pharmaceuticals, Lilly, Amgen, Immunomedics, Pfizer, Genentech, Bristol-Myers Squibb, Genomic Health. Research Funding: Bristol-Myers Squibb, ZIOPHARM Oncology, Lilly, Merck; Travel expenses: Merck, Spectrum Pharmaceuticals, Lilly, Amgen, Puma Biotechnology, Immunomedics, Genentech, Pfizer. Expert panel: Lilly. Adams: Advisory Board: BMS, Merck, Genentech (all uncompensated), research funding to institution: Genentech, Merck, Amgen, Novartis, BMS, Celgene. Mittendorf: serves on advisory boards for Merck, SELLAS Lifesciences, AstraZeneca/MedImmune, TapImmune, and Peregrine Pharmaceuticals, and received institutional research funding from Genentech, Astra Zeneca/MedImmune, and SELLAS Lifesciences., (© The Author(s) 2019.)