Background

Dato-DXd is an ADC comprising a humanized anti-TROP2 IgG1 mAb conjugated to a potent topoisomerase I inhibitor payload (DXd) via a stable tetrapeptide-based cleavable linker. Results from the ongoing phase I TROPION-PanTumor01 (NCT03401385) study showed encouraging antitumor activity of Dato-DXd in heavily pretreated patients (pts) with metastatic (m) NSCLC. Reported here are preliminary results in mTNBC; recruitment is ongoing.

Methods

TROPION-PanTumor01 is a 2-part study evaluating Dato-DXd IV Q3W in previously treated pts with solid tumors. Based on the dose-escalation phase limited to NSCLC pts, this expansion phase evaluated 6 mg/kg in pts with mTNBC that relapsed/progressed with standard treatment (TX). The primary endpoint was safety/tolerability. Secondary endpoints included efficacy assessed by ORR per RECIST v1.1 by blinded independent central review (BICR).

Results

As of the Jan 8, 2021, data cutoff, 24 pts had ≥1 dose (6 mg/kg, n=22; 8 mg/kg, n=2 [treated prior to 6-mg/kg dose selection]), with 18 (75%) still on TX and 6 (25%) discontinued for PD. Median age was 57 y (range, 32-82 y); 71% had ≥3 prior lines of therapy. Prior therapies were taxanes (83%), platinum-based TX (50%), immunotherapy (33%), and sacituzumab govitecan (8%). Among 21 pts (6 mg/kg, n=19; 8 mg/kg, n=2) evaluable for response (≥1 postbaseline tumor assessment or discontinued TX), ORR by BICR was 43% (9 PRs), with 5 confirmed and 4 pending confirmation. The disease control rate was 95% (20/21 pts). Dose reductions due to AEs occurred in 6 pts (25%); no pts discontinued TX due to AEs. Any grade (Gr) and Gr ≥3 TEAEs regardless of causality occurred in 100% and 33% of pts, respectively. Most common TEAEs (any Gr [≥40%], Gr ≥3) were nausea (63%, 0%), stomatitis (63%, 13%), fatigue (42%, 4%), and vomiting (42%, 0%). No Gr ≥3 TEAEs of diarrhea or decreased neutrophil count/neutropenia were reported. No cases of TX-related ILD (adjudicated) were observed.

Conclusions

Preliminary results show that Dato-DXd had highly encouraging antitumor activity and a manageable safety profile in pts with refractory mTNBC; further confirmatory studies are warranted.

Clinical trial identification

TROPION-PanTumor01 (NCT03401385) study.

Editorial acknowledgement

Medical editorial assistance was provided by Allison Lytle, PhD, from ArticulateScience LLC, which was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo Co, Ltd.

Funding

Daiichi Sankyo Co, Ltd.

Disclosure

A. Bardia: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Radius Health; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics ; Advisory/Consultancy, Research grant/Funding (institution): Biotheranostics Inc.; Research grant/Funding (institution), Travel/Accommodation/Expenses: Taiho; Advisory/Consultancy: Daiichi Sankyo/AstraZeneca; Advisory/Consultancy: Puma; Advisory/Consultancy, Travel/Accommodation/Expenses: Phillips; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Foundation Medicine. D. Juric: Advisory/Consultancy: Novartis, EMD Serono, Eisai, Genentech, Ipsen, Syros Pharmaceuticals, MapKure, Vibliome Therapeutics, Petra Pharma; Research grant/Funding (institution): Novartis, Genentech, Eisai, EMD Serono, Placon, Amgen, Syros Pharmaceuticals, InventisBio, Infinity Pharmaceuticals, Takeda, Pfizer. T. Shimizu: Advisory/Consultancy: Daiichi-Sankyo, AbbVie, Takeda Oncology, The Consortium on Harmonization of Institutional Requirements for Clinical Research (CHAIR) Joint Scientific Committee Review Member and External IRB Member of Phase 1 Trials in Hong Kong, HKSAR, China; Research grant/Funding (self): Novartis, AbbVie, Daiichi-Sankyo, Takeda Oncology, Eli Lilly, Loxo Oncology, Bristol-Myers Squibb, Eisai, Pfizer, AstraZeneca, Incyte, Symbio Pharmaceuticals, Chordia Therapeutics, 3D-Medicine, Five Prime, PharmaMar, Astellas . A. Tolcher: Leadership role: NEXT Oncology; Advisory/Consultancy: SOTIO Biotechnology; Advisory/Consultancy: Axlmmune; Advisory/Consultancy: Bayer; Advisory/Consultancy: Immunomet Therapeutics, Inc.; Advisory/Consultancy: Menarini; Advisory/Consultancy: Mersana; Research grant/Funding (institution): Naivre Pharma, Inc.; Research grant/Funding (institution): 3's Biotherapeutics; Research grant/Funding (institution): PMV Pharmaceuticals; Research grant/Funding (institution): Apros Therapeutics Inc.; Research grant/Funding (institution): Codiak Biosciences; Research grant/Funding (institution): Merck Sharp & Dohme; Speaker Bureau/Expert testimony: Immunogen. A. Spira: Advisory/Consultancy: Amgen, Incyte, Mirati Therapeutics, Novartis; Shareholder/Stockholder/Stock options: Eli Lilly; Honoraria (self): Amgen, AstraZeneca/MedImmune, Bristol-Myers-Squibb, CytomX Therapeutics, Janssen Oncology, Merck, Novartis, Takeda; Research grant/Funding (self): Daiichi Sankyo. T. Mukohara: Research grant/Funding (self): Daiichi Sankyo, Inc., Sysmex, MSD, Pfizer, Sanofi, Seagen, AstraZeneca; Honoraria (self): Eisai, Pfizer, Novartis, Chugai, Eli Lilly, AstraZeneca. A.E. Lisberg: Spouse/Financial dependant, Employment, Stock: Boston Scientific; Honoraria (self): AstraZeneca, Bristol-Myers-Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys; Advisory/Consultancy: AstraZeneca, Bristol-Myers-Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys; Research grant/Funding (institution): Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals, WindMIL. I. Krop: Honoraria (self): Daiichi Sankyo, Inc., Macrogenics, Novartis, Merck, Context Therapeutics, Taiho Oncology, Genentech/Roche, Seattle Genetics; Research grant/Funding (self): Genentech/Roche, Pfizer. K.P. Papadopoulos: Advisory/Consultancy: Bayer, ArQule, Basilea; Research grant/Funding (institution): AbbVie, MedImmune, Daiichi Sankyo, Regeneron, Sanofi, ARMO BioSciences, ArQule, Amgen, Calithera Biosciences, Incyte, Merck, Peloton Therapeutics, ADC Therapeutics, 3D Medicines, EMD Serono, Syros Pharmaceuticals, Mersana, OncoMed, MabSpace Biosciences, J. E. Hamilton: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Travel/Accommodation/Expenses: Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Mersana; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millennium, Taplmmune Inc., Medivation, Tesaro, H3 Biomedicine, Radius Health, Acerta Pharma, Takeda, Macrogenics, AbbVie, Immunomedics, F; Advisory/Consultancy: Astra Zeneca, Novartis, Silverback Therapeutics, Black Diamond Therapeutics, CytomX Therapeutics, Dantari, H3 Biomedicine, Merck, Novartis, Seattle Genetics, Eisai. S. Damodaran: Advisory/Consultancy: Tempus, Taiho Pharmaceutical, Pfizer; Travel/Accommodation/Expenses: Phillips Gilmore Oncology Communications; Honoraria (self): Novartis; Research grant/Funding (institution): EMD Serono, Guardant Health, Taiho Pharmaceutical, Novartis. J. Greenberg, W. Gu, F.M. Guevara, T. Jikoh: Full/Part-time employment: Daiichi Sankyo, Inc.; Shareholder/Stockholder/Stock options: Daiichi Sankyo, Inc. F. Kobayashi, Y. Kawasaki: Full/Part-time employment: Daiichi Sankyo, Inc. F. Meric-Bernstam: Full/Part-time employment: MD Anderson Cancer Center; Advisory/Consultancy: Inflection Biosciences; Speaker Bureau/Expert testimony: Chugai Pharma; Advisory/Consultancy, Research grant/Funding (institution): eFFECTOR Therapeutics; Travel/Accommodation/Expenses: Beth Israel Deaconess Medical Center; Honoraria (self): Mayo Clinic; Honoraria (self): Rutgers Cancer Institute of New Jersey; Research grant/Funding (institution): Novartis, AstraZeneca, Calithera Biosciences, Bayer, Aileron Therapeutics, Puma Biotechnology, CytomX Therapeutics, Jounce Therapeutics, Zymeworks, Curis, Pfizer, AbbVie; Guardant H; Research grant/Funding (institution), Travel/Accommodation/Expenses: Taiho Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): Debiopharm Group; Advisory/Consultancy: Samsumg Bioepis; Advisory/Consultancy: Spectrum Pharmaceuticals; Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy: Origimed; Advisory/Consultancy: Xencor; Advisory/Consultancy: Mersana; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Silverback Therapeutics; Advisory/Consultancy: Immunomedics.

Background

About 40% of patients with a metastatic HER2+ breast cancer (BC) develop brain metastases (BM). A better understanding of clinical features of patients with HER2+ BC with BM is required.

Methods

A total of 2948 patients of the Brain Metastases in Breast Cancer (BMBC) Registry were available for this analysis, 1311 of them had a HER2+ subtype.

Results

Patients with a HER2+ BC and BM were,compared to HER2- patients, slightly younger at BC diagnosis (median 52 vs 53 years, p<0.001) and BM diagnosis (median 55 vs 58 years, p<0.001), had a higher pathological complete response rate after neoadjuvant chemotherapy (21.5 vs 12.2%, p=0.002), higher tumor grading (G3 59.5 vs 56.5%, p<0.001) and had less common extracranial metastases (ECM) at BM diagnosis (77.7 vs 80.0%, p<0.001). HER2+ patients had significantly more often BM in the posterior fossa (57.9 vs 49.0%, p<0.001) but less common leptomeningeal metastases (LM) (9.3 vs 19.1%, p<0.001). Hormone-receptor-positive HER2+ patients were younger at BC diagnosis (median 50 vs 53 years, p=0.03), had a smaller initial BC (<5cm: 78.4 vs 66.3%, p=0.002), a lower grading of the primary tumor (G1/G2: 46.1 vs 29.9%, p<0.001) and more often LM (11.3 vs 6.8%, p=0.007). The median overall survival (OS) in all HER2+ patients was 13.2 months (95% CI 11.4-14.4). The following factors were associated with a worse OS (multivariate analysis): older age (≥60 vs <60 years: Hazard Ratio [HR] 1.63, p<0.001), lower performance status (ECOG 2-4 vs 0-1: HR 1.58, p<0.001), greater number of BM (2-3 vs 1 BM: HR 1.36; ≥4 vs 1 BM: HR 1.53, p=0.003; overall p=0.012), BM in fossa anterior (HR 1.71, p<0.001), LM (HR 1.62, p=0.027), BM with neurological symptoms at diagnosis (HR 1.38, p=0.029), ECM at diagnosis of BM (HR 1.44, p=0.02) and the absence of targeted therapy (HR 0.625, p=0.001). Although progression-free survival did not differ in HER2+ patients according to hormone-receptor status, a significantly better OS could be observed for hormonereceptor-positive patients (median 14.3 vs 10.9 months, p=0.027).

Conclusions

The performed analysis identified factors associated with prognosis of HER2+ patients with BM. Further research is needed to understand the factors determining the longer survival of HER2+ hormonereceptor-positive patients.

Legal entity responsible for the study

German Breast Group Forschungs GmbH.

Funding

Has not received any funding.

Disclosure

I. Witzel: Honoraria (institution): Amgen; Honoraria (institution): AstraZeneca; Honoraria (institution): MSD; Honoraria (institution): Novartis; Honoraria (institution): Pierrre Fabre Pharma; Honoraria (institution): Pfizer; Honoraria (institution): Roche; Honoraria (institution): Sanofi-Pfizer. C. Denkert: Honoraria (institution), Oncobiome project: European Commission H2020; Honoraria (institution), INTEGRATE-TN project: German Cancer Aid Translational Oncology; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Molecular Health; Honoraria (institution): Myriad; Honoraria (self): Merck; Shareholder/Stockholder/Stock options, Cofounder/shareholder until 2016: Sividon diagnostics; Licensing/Royalties: VMScope digital pathology software; Licensing/Royalties: WO2020109570A1 - cancer immunotherapy; Licensing/Royalties: WO2015114146A1 and WO2010076322A1- therapy response. S. Loibl: Honoraria (institution), honoraria for lectures and ad boards paid to institute: AbbVie; Honoraria (institution), honoraria for lectures and ad boards paid to institute: Celgene; Honoraria (institution), honorarium for lectures paid to institute: PriME/Medscape; Honoraria (self), lecture: Chugai; Honoraria (self), Honoraria (institution), honoraria paid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), advisor honorarium paid to institute: BMS; Honoraria (institution), advisor honorarium paid to institute: Puma; Honoraria (institution), paid to institute: Immunomedics; Honoraria (institution), honorarium for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pierre Fabre; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Merck; Honoraria (institution), advisor honorarium paid to institute: EirGenix; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Amgen; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Novartis; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), grant and honorarium paid to institute: Roche; Honoraria (institution), paid to institute: Seagen; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0. V. Mueller: Advisory/Consultancy: Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro and Nektar; Speaker Bureau/Expert testimony: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seagen and consultancy honoraria from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Nektar; Honoraria (institution): Novartis, Roche, Seattle Genetics, Genentech. All other authors have declared no conflicts of interest.

Background

About a half of breast cancers traditionally classified as HER2-negative show a low HER2 expression (IHC 1+ or IHC 2+ and ISH negative) that can be targeted by new antibody-drug conjugates. There is no data on the evolution of HER2-low status from primary tumor to relapse.

Methods

Patients with matched primary and relapsed breast cancer samples from two Institutions (IOV-IRCCS Padova and Treviso Hospital) were included. HER2 was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. Cases diagnosed between 2007 and 2013 were reviewed by IHC to comply with the cut-off of >10% cells staining for HER2 positivity. Moreover, 100 random samples were reviewed by a blinded pathologist: agreement with the original report was 80%. HER2-neg cases were sub-classified as HER2-low (IHC 1+, or IHC 2+ and ISH not amplified), or HER2-0 (IHC 0).

Results

575 patients were included. Primary tumor phenotype was: 59% luminal-like (HR+/HER2-neg), 25% HER2-pos, 16% triple-negative. The proportion of HER2-low cases was 34% on the primary tumor and 38% on the relapse samples. Among HER2-neg cases, HER2-low status was more frequent in Luminal-like vs triple-negative tumors (47% vs 41% on primary tumor samples, p=0.268; 54% vs 40% on relapse samples, p=0.006). The overall rate of HER2 discordance was 38% (Table), mostly represented by HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%). A minority (9%) of cases lost or acquired HER2-positivity. Among patients with a primary HER2-neg tumor, the rate of HER2 discordance was higher in luminal-like vs triple-negative cases (45% vs 35% p=0.080). This difference was mostly driven by cases switching from HER2-0 to HER2-low: 40% of luminal-like/HER2-0 vs 24% of triple-negative/HER2-0 patients (p=0.088). Table: 4MO

Conclusions

HER2-low expression is highly unstable during disease evolution. Relapse biopsy in case of a primary HER2-0 tumor may open new opportunities for treatment in a relevant proportion of patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Fassan: Advisory/Consultancy, Research grant/Funding (institution), outside the submitted work: Astellas Pharma; Advisory/Consultancy, outside the submitted work: Diaceutics; Advisory/Consultancy, outside the submitted work: Tesaro; Research grant/Funding (institution), outside the submitted work: QED Therapeutics. P.F. Conte: Research grant/Funding (institution), outside the submitted work: Merck; Honoraria (self), Research grant/Funding (institution), outside the submitted work: Roche; Honoraria (self), outside the submitted work: Novartis; Honoraria (self), outside the submitted work: Lilly. V. Guarneri: Honoraria (self), Research grant/Funding (institution), outside the submitted work: Roche; Honoraria (self), outside the submitted work: Novartis; Honoraria (self), outside the submitted work: Eli Lilly. M.V. Dieci: Honoraria (self), outside the submitted work: Genomic Health; Honoraria (self), outside the submitted work: Eli Lilly; Honoraria (self), outside the submitted work: Celgene. All other authors have declared no conflicts of interest.

Background

Premenopausal breast cancer patients have an increased long-term risk for fatal disease, and endocrine therapy benefit including ovarian suppression is unexplored. Here for the first time, we assessed the 20-year benefit of goserelin and tamoxifen stratified by the molecular 70-gene signature risk prediction in premenopausal women in a randomized trial.

Methods

In 1990-1997, n=924 premenopausal patients (age range 26-57, median 46) were randomized into 4 well-balanced trial arms; 2 years of goserelin, tamoxifen, the combination of goserelin and tamoxifen, or no endocrine therapy. Lymph-node positive women (n=459) received standard chemotherapy. Swedish high-quality National registries allowed long-term (20 years) complete follow-up after randomization. Immunohistochemistry of the clinically used breast cancer markers was performed in 2020 (n=729) together with Agilent microarray profiling (n=589). The 70-gene signature classified patients into low or high risk of recurrence. Kaplan-Meier analysis and multivariable Cox proportional hazard regression were used to assess the endocrine therapy benefit.

Results

Adjusted multivariable analyses show that in estrogen receptor (ER)-positive patients (n=610) goserelin, tamoxifen, and the combination of goserelin and tamoxifen reduced the 20-year risk of distant recurrence compared to no endocrine therapy, see table. Stratification by the 70-gene signature showed a significant benefit in low risk patients (n=306) from tamoxifen therapy (Hazard Ratio [HR]=0.38, 95% Confidence Interval [CI]: 0.18-0.82), whereas high risk patients (n=159) had a significant benefit from goserelin therapy (HR=0.22, 95% CI: 0.10-0.49). Similar findings were seen when using breast cancer-specific survival as the end-point. Table: LBA1

Long-term (20 year) risk of distant recurrence adjusted for tumour size, grade, lymph-node status, PR, HER2, Ki-67, chemotherapy, and radiotherapy

Conclusions

This study with unique long-term follow-up in premenopausal patients suggests that high risk patients significantly benefit from goserelin, whereas low risk patients benefit from tamoxifen.

Legal entity responsible for the study

The authors.

Funding

The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare (FORTE), and The Swedish Cancer Society (Cancerfonden).

Disclosure

L. van 'T Veer: Shareholder/Stockholder/Stock options, Full/Part-time employment, Dr van't Veer is one of the inventors of the MammaPrint 70-gene risk signature (patent no WO2002103320): Agendia.

Background

ALP + fulvestrant is approved for PIK3CA-mutated, HR+/HER2– advanced BC in the US and EU. HG is an on-target adverse event (AE) of ALP and the most common all grade (G) and G3/4 AE in the phase III SOLAR-1 trial. Antihyperglycemic agents (AHAs) and ALP dose modifications (mods) and discontinuations (discs) were used to manage this AE (Table). We present a pooled risk factor model using safety sets of the phase I X2101 (NCT01219699) and SOLAR-1 (NCT02437318) trials and its application to SOLAR-1 data.

Methods

Pts (505) were randomly divided into training (405 pts) and testing sets (100 pts). Baseline factors for HG were identified, multiple models tested, and a random forest model was used to categorize pts as high or low risk for G3/4 HG based on 5 baseline factors (fasting plasma glucose [FPG], BMI, HbA1c, monocyte counts, and age). Performance metrics will be presented.

Results

The training set identified G3/4 HG in 126/131 high (96.2%) vs 3/274 low risk (1.09%) pts, and was validated in the testing set with 20/33 high (60.6%) vs 12/67 low risk (17.9%) pts. A 2-month (mo) analysis of G3/4 HG risk confirmed decreased probability at lower risk scores (area under the curve: training set = 0.991, testing set = 0.767). In all pts in the ALP arm of SOLAR-1, the model found a higher incidence of all-G and G3/4 HG, use of multiple AHAs, and more dose mods and discs in the high vs low risk pts (Table). There was no difference in median PFS in high (11.0 mo) vs low risk (10.9 mo) pts in the ALP arm with PIK3CA mutations. Table: 96MO

Conclusions

Risk modeling identified 5 baseline factors (FPG, BMI, HbA1c, monocyte counts, and age) associated with a higher probability of ALP-induced G3/4 HG. High risk pts had higher rates of AHAs and ALP mods. This model could be used clinically to identify pts at high risk for ALP-induced HG. Regardless of risk, pts with PIK3CA mutations derived a similar PFS benefit from ALP.

Clinical trial identification

NCT02437318, NCT01219699.

Editorial acknowledgement

This abstract was developed with editorial assistance provided by Daniele Cary, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

J. Rodon: Honoraria (self), Advisory/Consultancy: Novartis, Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Peptomyc, Merck Sharp & Dohme, Kelun Pharmaceuticals/Klus Pharma, Spectrum Pharmaceuticals, Inc., Pfizer, Roche Pharmaceuticals, Ellipses Pharma, Certera, Bayer, Molecular Partners, Nov; Research grant/Funding (institution): Bayer, Novartis, Blueprint Pharmaceuticals, Spectrum Pharmaceuticals, Tocagen, Symphogen, BioAlta, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GlaxoSmithKline, Ipsen; Travel/Accommodation/Expenses: ESMO, Department of Defense, Merck Sharp & Dohme, Louisiana State University, Kelun Pharmaceuticals/Klus Pharma, Huntsman Cancer Institute, Cancer Core Europe, Karolinska Cancer Institute, King Abdullah International Medical Research Center, Bayer, WIN Co; Non-remunerated activity/ies: European Journal of Cancer, VHIO/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, SOLTI, Elsevier, GlaxoSmithKline. D. Demanse: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. H.S. Rugo: Research grant/Funding (institution): Plexxikon; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution), Travel/Accommodation/Expenses: OBI Pharma; Research grant/Funding (institution): Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Celsion; Research grant/Funding (institution): Merck; Travel/Accommodation/Expenses: Roche/Genentech; Travel/Accommodation/Expenses: Bayer. F. André: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche. I. Mayer: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: Puma; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Immunomedics; Honoraria (self), Advisory/Consultancy: Macrogenics; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: Cylacel. H. Burris: Honoraria (institution), Research grant/Funding (institution): AstraZeneca, Incyte, Novartis, Bayer, Pfizer; Honoraria (institution): FORMA Therapeutics, Celgene, Daiichi Sankyo, HCA Healthcare/Sarah Cannon, GRAIL; Research grant/Funding (institution): Roche/Genentech, Bristol-Myers Squibb, MedImmune, Macrogenics, Boehringer Ingelheim, Lilly, Seattle Genetics, Merck, Agios, Jounce Therapeutics, Moderna, CytomX, GlaxoSmithKline, Verastern, Tesaro, BioMed Valley Discoveries, TG Therapeutics, Vertex, eFFEC. A. Farooki: Leadership role: Novartis. H. Hu, I. Lorenzo, C. Quadt: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. D. Juric: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: EMD Serono. All other authors have declared no conflicts of interest.