Background

MONARCH 2 led to abemaciclib + fulvestrant approval in pts with HR+, HER2- ABC with disease progression on prior endocrine therapy and demonstrated significant OS benefit. MONARCH 3 led to abemaciclib + NSAI approval as initial therapy in postmenopausal pts with HR+, HER2- ABC with significant improvement in progression-free survival (PFS). Here we report the second interim analysis (IA2) OS results for MONARCH 3, an analysis included in the European Product Label by request of EMA.

Methods

MONARCH 3 is a 2:1 randomized, double-blind, placebo-controlled Phase 3 study of NSAI +/- abemaciclib. Detailed study information, including the primary endpoint of PFS are published (Goetz, JCO 2017). OS is a key secondary endpoint and this prespecified OS IA2 (data cut 2 Jul 2021) was scheduled after ∼252 events in the ITT population (80% of planned events for final OS analysis), using a stratified log-rank test and applying a pre-defined error spending strategy to assess significance in both the ITT and the subgroup with visceral disease (sVD).

Results

493 pts were randomized to receive NSAI + abemaciclib (n=328) or placebo (n=165). At IA2, with 70.2 months median follow-up, in the ITT the median OS (mOS) was 67.1 months for abemaciclib + NSAI vs 54.5 months for placebo + NSAI (HR=0.754, 95% CI: 0.584-0.974, 2-sided p=0.0301). In sVD, the mOS was 65.1 months for abemaciclib + NSAI vs 48.8 months for placebo + NSAI (HR=0.708, 95% CI: 0.508-0.985; 2-sided p=0.0392). According to the alpha spending procedure, the critical boundaries for declaring significance in both groups were not met for IA2. Follow-up is ongoing for final OS analysis (expected 2023). Safety data were consistent with the known profile of abemaciclib.

Conclusions

In the second interim prespecified overall survival analysis from MONARCH 3, longer OS was observed in both the ITT and sVD (an increase in the median OS by >12 months with the addition of abemaciclib to NSAI), however neither met the threshold for formal statistical significance according to the alpha spend procedure. Final OS analysis is planned when at least 315 OS events in ITT and 189 in sVD are observed.

Clinical trial identification

NCT02246621.

Editorial acknowledgement

Trish Huynh, employee of Eli Lilly and Company (Indianapolis, IN) provided medical writing support.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

M.P. Goetz: Other, Personal, Other: Genomic Health; Financial Interests, Institutional, Other, consulting fees to Mayo: Eli Lilly and Company; Other, Institutional, Other, consulting fees to Mayo: Biovica, Novartis, Sermonix, Context Pharm, Pfizer, AstraZeneca, Eagle Pharmaceuticals; Financial Interests, Institutional, Research Grant: Pfizer, Eli Lilly and Company, Sermonix; Other, Institutional, Advisory Board, Honoraria to Mayo: ARC Therapeutics, Blueprint Medicines, Sanofi Genzyme, Biotheranostics; Financial Interests, Personal, Other, CME presentation: Research to Practice, Clinical Education Alliance, Medscape; Financial Interests, Personal, Other, Session moderator: Curio; Financial Interests, Personal, Other, Honoraria to Mayo: Total Health Conferencing. M. Toi: Financial Interests, Personal, Research Grant, Lecture Honoraria: Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Shimadzu, Yakult; Other, Personal, Other, Manuscript Fee: Kyowa-Kirin; Financial Interests, Research Grant: JBCRG association, Astellas, AFI technologies, Shionogi, GL Science, KBCRN association; Financial Interests, Personal, Other, Research grant, Lecture honoraria, Advisory role for a drug development: Daiichi-Sankyo; Financial Interests, Personal, Research Grant, Lecture Honoraria, An advisory role: Eli Lilly and Company; Other, Personal, Other, Lecture Honoraria: MSD, Exact Science, Novartis; Other, Other, Honoraria for an advisory meeting: BMS; Financial Interests, Personal, Other, Research fund and honoraria for lecture: Nippon Kayaku; Other, Advisory role: Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Financial Interests, Other, Advisory role, research grant: Luxonus; Other, Member of the Board of Directors: JBCRG association, Organization for Oncology and Translational Research, Kyoto Breast Cancer Research Network. J. Huober: Financial Interests, Personal, Other, Grant: Eli Lilly and Company, Novartis, Celgene; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer; Other, Personal, Other: Gilead; Financial Interests, Personal, Other: Daiichi Sankyo, AstraZeneca, Seagen, MSD, AbbVie; Financial Interests, Other, Grant: Hexal. J. Sohn: Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Eli Lilly and Company, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim. O. Tredan: Non-Financial Interests, Personal, Other: Eli Lilly and Company, Roche, Novartis-Sandoz, AstraZeneca, Pfizer; Non-Financial Interests, Personal, Other, Grant: MSD; Financial Interests, Other, Grant: BMS; Other, Personal, Other: Pierre Fabre, Eisai, Seagen, Daiichi-Sankyo, Stemline, Gilead. M. Campone: Financial Interests, Institutional, Research Grant: Pfizer, AstraZeneca, Sanofi, Pierre Fabre, Takeda, AbbVie, Servier, Sandoz, Accord; Financial Interests, Personal, Other, Speaker fees: Novartis, Eli Lilly and Company. S. Paluch-Shimon: Other, Research Grant: Pfizer; Other, Speaker’s Bureau, Honoraria, Consultancy: Roche, AstraZeneca, Novartis, Pfizer, Exact Sciences. G. van Hal: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Other, Employee: Eli Lilly and Company. A. Shahir: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Other, Employee: Eli Lilly and Company. H. Iwata: Financial Interests, Other, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Eli Lilly and Company, MSD, Pfizer; Financial Interests, Advisory Role: Daichi-Sankyo, Chugai, Pfizer, Sanofi, Lilly, MSD, Pfizer, Novartis; Financial Interests, Research Grant: Daiichi-Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer, Novartis, Amgen. S. Johnston: Financial Interests, Personal, Other, Consulting/Advisory Role: Eli Lilly, Puma Biotechnology; Financial Interests, Personal, Other, Consulting/Advisory Role and Speakers Bureau: AstraZeneca, Pfizer, Novartis; Financial Interests, Personal, Other, Speakers Bureau: Eisai, Roche/Genentech; Financial Interests, Institutional, Funding, Research funding for lab studies and clinical trials: Pfizer; Financial Interests, Institutional, Funding, Research funding for lab studies: Puma Biotechnology; Financial Interests, Institutional, Funding, Research funding for clinical trials: Eli Lilly, AstraZeneca, Novartis, Roche/Genentech. All other authors have declared no conflicts of interest.

Background

Dalpiciclib (dalp), a novel CDK4/6 inhibitor, with fulvestrant improved PFS in patients (pts) with HR+/HER2- advanced breast cancer (ABC) progressing after endocrine therapy (ET) in the phase 3, DAWNA-1 trial (Nature Medicine 2021). Here we assessed dalp with ET in the 1^st-line setting.

Methods

DAWNA-2 was a randomized, multicenter, double-blind, phase 3 trial done in 42 centers in China. Pts with untreated HR+/HER2- locally recurrent or metastatic BC, and any menopausal status were randomized 2:1 to receive dalp (150 mg, po, qd, d1-21, q4w) or placebo + letrozole (2.5 mg, po, qd) or anastrozole (1 mg, po, qd). The primary endpoint was PFS per investigator (INV). A prespecified interim analysis was done after 186 (70.5% of total expected) PFS events occurred (Jun 1, 2022), and the corresponding superiority boundary was 1-sided P <0.0076.

Results

456 pts were randomized to dalp + letrozole/anastrozole (N=303) or placebo+ letrozole/anastrozole (N=153). With a median follow-up of 21.7 and 21.4 mo respectively, PFS per INV was significantly improved in the dalp group vs the placebo group (median, 30.6 mo [95% CI 30.6-NR] vs 18.2 mo [16.5-22.5]; HR 0.51 [95% CI 0.38-0.69], 1-sided P <0.0001). PFS benefit with dalp was evident regardless of menopausal status (Table 1). ORR and DoR per INV also favored the dalp group (Table 1). The most frequent grade ≥3 AEs in the dalp group was neutropenia (85.8% [grade 3/4, 64.6%/21.2%] vs 0 in the placebo group) and leukopenia (66.6% [grade 3/4, 65.9%/0.7%] vs 0). SAEs occurred in 11.9% in the dalp group and 6.5% in the placebo group; 4.0% and 2.0% discontinued any treatment due to AEs respectively. Table: LBA16

Efficacy summary

Conclusions

Adding dalp to letrozole/anastrozole significantly prolonged PFS in HR+/HER2- ABC, with manageable toxicities. Dalp is the 4^th CDK4/6 inhibitor showing survival benefit with letrozole or anastrozole in untreated HR+/HER2- ABC, or with fulvestrant in pretreated HR+/HER2- ABC, in addition to palbociclib, ribociclib and abemaciclib.

Clinical trial identification

NCT03966898.

Editorial acknowledgement

Editorial assistance was provided by Xiuzhi Wu (Hengrui Pharmaceuticals).

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co. Ltd.

Disclosure

B. Xu: Financial Interests, Personal, Research Grant: Hengrui; Financial Interests, Personal, Advisory Role: Novartis, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Roche, Pfizer. Z. Tong: Financial Interests, Personal, Research Grant: Hengrui, Novartis, Company, Bio-Thera, Eli Lilly. S. Jiang: Financial Interests, Personal, Full or part-time Employment: Hengrui. N. Bayaxi: Financial Interests, Personal, Full or part-time Employment: Hengrui. X. Zhu: Financial Interests, Personal, Full or part-time Employment: Hengrui. All other authors have declared no conflicts of interest.

Background

Pts with HR+/HER2- mBC are treated with endocrine-based therapy (ET), followed by single-agent chemotherapy (CT), with increasingly shorter durations of benefit. SG is an anti–Trop-2 antibody-drug conjugate approved for triple-negative mBC with ≥2 prior therapies (≥1 in the metastatic setting). In TROPiCS-02 (NCT03901339), SG showed significant progression-free survival (PFS) benefit vs TPC in ET resistant HR+/HER2- mBC (HR, 0.66; P<0.001; median 5.5 vs 4.0 mo; Rugo, et al. ASCO 2022). Here, we report the planned TROPiCS-02 OS 2nd interim analysis.

Methods

Eligible pts with HR+/HER2- mBC who received prior taxane, ET, CDK4/6 inhibitor, and 2-4 prior CTs were randomized 1:1 to receive SG (10 mg/kg IV d1 and 8, every 21d) or TPC until progression or unacceptable toxicity. Primary endpoint was PFS by BICR with key secondary endpoint of OS. Per protocol, OS was analyzed after ∼350 events. In the statistical testing hierarchy, objective response rate (ORR) and pt-reported outcomes are tested sequentially if OS is significant.

Results

In total, 543 pts were randomized to receive SG (n=272) vs TPC (n=271). Pts had a median of 3 prior CTs for mBC; 95% had visceral metastases. At data cut-off on July 1, 2022 (median follow-up,12.5 mo), 390 OS events occurred. SG significantly improved OS (median 14.4 vs 11.2 mo; HR, 0.79; P=0.020), ORR, global health status/QoL, and fatigue vs TPC (Table). Safety of SG was consistent with prior reports with no new safety signals identified. Table: LBA76

Conclusions

SG demonstrated statistically significant and clinically meaningful improvement in OS, and significant improvement in ORR and QoL vs TPC with manageable safety in pts with ET-resistant HR+/HER2- mBC, a population with limited treatment options. These data support the use of SG as a novel therapy for pts with pre-treated HR+/HER2- mBC.

Clinical trial identification

NCT03901339.

Editorial acknowledgement

Shala Thomas from Team Sciences provided editorial support.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

H.S. Rugo: Financial Interests, Institutional, Other, Honoraria: Puma Biotechnology, Mylan, Samsung BioepisBioepis; Financial Interests, Institutional, Research Grant: Macrogenics, OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals. A. Bardia: Financial Interests, Institutional, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/Astra Zeneca, Eli Lilly].; Financial Interests, Institutional, Other, Consulting Fees: Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/Astra Zeneca, Phillips, Eli Lilly, Foundation Medicine]. F. Marmé: Financial Interests, Institutional, Research Grant: Roche, Novartis, AstraZeneca, GSK/Tesaro, MED, Clovis, Vaccibody, Gilead Sciences, Eisai; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca, TESARO/GSK, Pfizer, EISAI, Gilead, GenomicHealth; Financial Interests, Institutional, Other, Consulting Fees: VACIIBODY; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis, GSK/

Background

APOBEC mutagenesis is enriched in MBCs. The predictive role of APOBEC and other mutational processes on standard regimens in the MBC setting is largely unknown.

Methods

We retrieved clinical and genomic data of 4,595 BCs that underwent targeted sequencing by an FDA-cleared panel comprising >400 genes. Mutational signatures were computed by the SigMA algorithm for samples with at least 5 single nucleotide variants and manually reviewed. BCs were classified as APOBEC+, HRD+ or APOBEC-/HRD- based on the dominant mutational process as defined by SigMA. Progression-free survival (PFS) to any line (L) of therapy was assessed using univariate and multivariate Cox models.

Results

APOBEC+ and HRD+ were found at higher proportion in MBCs than in primary tumors (24% and 24% vs 15% and 13%; p<0.001). APOBEC+ were highly represented in ER+/HER2- (19%) and HER2+ (47%) subtypes, while HRD+ in triple-negative (36%). Lobular BCs had a higher proportion of APOBEC+ than HRD+ and APOBEC-/HRD- (34% vs 10% vs 21%, p<0.001). ER+/HER2- MBCs with APOBEC displayed lower ESR1 hotspot mutations (p<0.001). Survival analyses were restricted to patients with available pre-treatment samples. In ER+/HER2- MBCs treated with 1L or 2L ET monotherapy (n=395), APOBEC+ tumors were independently associated to shorter mPFS (HR 1.6, 95%CI 1.2-2.2, p=0.001), regardless of the ET agent. APOBEC+ and HRD+ MBCs were associated with lower mPFS on 1L CDK4/6i+ET (n=419) than APOBEC-/HRD- (HR 1.5, 95%CI 1.1-2, p=0.01 and HR 1.7, 95%CI 1.2-2.5, p=0.006, respectively), regardless of ET partner. HRD+ BCs had a reduced mPFS on 2L (n=207) and 3L (n=372) of CDK4/6i+ET (HR 2.1, 95%CI 1-4.1, p=0.03 and HR 1.8, 95%CI 1.3-2.5, p=0.001, respectively).

Conclusions

Patients with APOBEC+ and HRD+ ER+/HER2- MBCs experience shorter survival on ET +/- CDK4/6i, suggesting that the genomic instability conferred by APOBEC and HRD results in early resistance. Novel treatments tailored on these BC subgroups are needed. Additional genomic analyses to unravel mutational patterns related to APOBEC and HRD in this setting are underway.

Legal entity responsible for the study

Memorial Sloan Kettering Cancer Center.

Funding

Has not received any funding.

Disclosure

P. Razavi: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Foundation Medicine, Natera, Epic Science, Inivata; Financial Interests, Institutional, Funding: Grail Inc, Novartis; Non-Financial Interests, Advisory Role: Tempus. N. Riaz: Financial Interests, Personal and Institutional, Funding, Research support: REPARE Therapeutics, Repertoire Immune Medicines, Pfizer, BMS. J.S. Reis-Filho: Financial Interests, Personal, Other, Consultant: Goldman Sachs, Eli Lilly; Financial Interests, Personal, Other, Member of the Scientific Advisory Board and Consultant: Repare Therapeutics, Paige.AI; Financial Interests, Personal, Advisory Board: Personalis, Roche Tissue Diagnostics; Financial Interests, Personal, Invited Speaker: Grupo Oncoclinicas; Financial Interests, Personal, Stocks/Shares: Repare Therapeutics; Financial Interests, Personal, Other, Stock options: Paige.AI. S. Chandarlapaty: Financial Interests, Personal, Advisory Board: Sanofi, Lilly, Novartis, Inivata, AstraZeneca, Ultivue, Totus Medicines; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Paige.ai, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Lilly, Novartis, Sanofi. All other authors have declared no conflicts of interest.

Background

Overexpression of the ectoenzyme CD73 is involved in the generation of immunosuppressive adenosine in the tumor microenvironment and is associated with poor prognosis in patients (pts) with TNBC. Blocking CD73 with oleclumab may enhance the antitumor response to the combination of an anti-PD-L1 with chemotherapy in TNBC.

Methods

Women with previously untreated, inoperable locally advanced or metastatic TNBC were randomized to weekly carboplatin (AUC 1.5) and paclitaxel (80 mg/m2) x12 combined with durvalumab (1500 mg q4w) with (Arm A) or without (Arm B) oleclumab (3000 mg q2w x5 then 3000 mg q4w) in 16 centers in France and Belgium. Maintenance with durvalumab +/- oleclumab was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Pts were stratified by PD-L1 and CD73 IHC expression assessed on baseline tumor tissue. The primary endpoint was clinical benefit rate (CBR; complete/partial response and stable disease according to RECIST 1.1) at week 24. A prespecified interim analysis was planned after CB assessment of the first 34 evaluable pts per arm.

Results

127 pts were recruited and assessed for eligibility (63 in arm A, 64 in arm B) between June 2019 and June 2021 when the recruitment was stopped due to the results of the interim analysis that crossed the futility boundary. Pts under treatment were allowed to continue with durvalumab+/-oleclumab. At data cutoff (July 4, 2022), the median follow-up was 13.2 months with a CBR of 42.9% in arm A and 43.3% in arm B (one-sided Fisher's exact, p=0.61) with no significant difference according to PD-L1 or CD73 status. PFS was not significantly different among arms: median PFS 6 months in arm A vs. 7.7 months in arm B, one-sided log rank test, p=0.89. The safety profile was similar in both arms. 9 patients in each arm are still under immunotherapy maintenance.

Conclusions

The addition of oleclumab to durvalumab with carboplatin/paclitaxel did not increase CBR at week 24 in first-line advanced TNBC. Ongoing translational research aims to better understand the mechanisms of responses to the study combination.

Clinical trial identification

Sponsor Protocol Number: IJB-SYNERGY-012017, Issue date 30/06/2018.

Legal entity responsible for the study

Institut Jules Bordet, Brussels, Belgium.

Funding

AstraZeneca/MedImmune.

Disclosure

L. Buisseret: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Funding: Fondation Contre le Cancer. D. Loirat: Financial Interests, Personal, Advisory Board, Honoraria: AstraZeneca, Eli Lilly, Immunomedics, MSD, Pfizer, Roche, 4D Pharma, Daiichi Sankyo, Novartis, Gilead; Financial Interests, Personal, Royalties, Travel support: Pfizer, Roche, MSD, AstraZeneca. P.G. Aftimos: Financial Interests, Personal, Advisory Board, Consulting: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte; Financial Interests, Personal, Advisory Board, Honoraria: Synthon, Amgen, Novartis, Gilead; Financial Interests, Personal, Royalties, Travel support: Amgen, MSD, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Roche. K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Roche, Vifor Pharma, Eli Lilly, Pierre Fabre, McCann Health, Roularta, Teva, Gilead Sciences, Pfizer, Gilead, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Novartis, Eli Lilly, Mundi Pharma, MSD, Medscape, MSD; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Gilead, Novartis, MSD, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Sanofi; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium; Non-Financial Interests, Advisory Role, External Scientific Advisor: European Medicine Agency. C. Maurer: Financial Interests, Personal, Royalties, Travel support: Mundipharma, Amgen, Servier Deutschland GmbH, AbbVie; Financial Interests, Personal, Advisory Board, Honoraria: AbbVie; Financial Interests, Personal, Advisory Board: Celgene/ BMS. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: AstraZeneca, Pierre Fabre, Roche, Amgen, Servier, Sanofi, MSD, BMS. D. Taylor: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eli Lilly, Medscape, Roche, Novartis, Agendia, MSD; Financial Interests, Personal, Royalties: Pfizer, Roche, AstraZeneca . F. Clatot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Roche, Merck, BMS, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche; Financial Interests, Personal, Royalties: AstraZeneca, Roche, Eli Lilly, Merck, BMS, MSD, Pfizer . T.F.A. van den Mooter: Financial Interests, Personal, Advisory Board: Pfizer, Astellas, Bayer, MSD; Financial Interests, Personal, Royalties: Roche, Merck, Pfizer. J. Canon: Financial Interests, Personal, Advisory Board: Lilly, Roche, Pfizer, BMS, Daiichi; Financial Interests, Institutional, Research Grant: Roche, BMS, Amgen. F.P. Duhoux: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, Gilead, Novartis, Pfizer, Pierre Fabre, Roche and Seagen, Amgen, AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Pierre Fabre, Roche and Seagen, Gilead; Financial Interests, Personal, Royalties: Amgen, Pfizer, Roche, Teva. F. Bazan: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, AstraZeneca, Clovis, SeaGen, Daiichi Sankyo. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis; Financial Interests, Personal, Invited Speaker: Seattle Genetic, Zodiac, Libbs, Pierre Fabre; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE. M. Ignatiadis: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Independent monitoring committee: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Natera; Non-Financial Interests, Invited Speaker: EORTC; Non-Financial Interests, Officer: EORTC. M. Piccart: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, MSD, Novartis, Pfizer; Financial Interests, Personal, Other, Consultant: Camel-IDS/Precirix; Financial Interests, Personal, Advisory Board: Immunomedics, Menarini, Odonate, Seattle Genetics, Immutep, SeaGen, Gilead, NBE Therapeutics, Frame Therapeutics; Financial Interests, Personal, Advisory Board, Consultant and invited speaker: Roche-Genentech; Financial Interests, Personal, Invited Speaker, Scientific Board: Oncolytics; Financial Interests, Institutional, Research Grant: AstraZeneca, Immunomedics, Lilly; Financial Interests, Institutional, Funding: Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon. All other authors have declared no conflicts of interest.