Background

Atezo, which targets PD-L1, is effective in several cancers. Blocking tumour-associated VEGF may promote T-cell infiltration into the tumour bed and boost anti-tumour immune response, justifying combination with bev. Dual VEGF-A and PD-L1 blockade is effective in lung and hepatocellular cancers.

Methods

IMagyn050 (NCT03038100) enrolled patients (pts) with newly diagnosed untreated stage III/IV OC who underwent either primary cytoreductive surgery (PCS) with gross residual disease or neoadjuvant chemotherapy (NACT) and interval surgery. Eligible pts were randomised 1:1 to atezo 1200 mg or pbo cycles 1–22, with paclitaxel 175 mg/m² + carboplatin AUC6 cycles 1–6 + bev 15 mg/kg cycles 2–22 (PCS pts), omitting peri-operative bev in NACT pts. Cycles were repeated q3w. Stratification factors were: stage (III vs IV), ECOG PS (0 vs 1/2), PD-L1 staining in immune cells (IC <1% vs ≥1% [PD-L1+]) and treatment strategy (PCS vs NACT). The co-primary endpoints were investigator-assessed progression-free survival (PFS; RECIST v1.1) and overall survival (OS) in the intent-to-treat (ITT) and PD-L1+ populations. PFS was tested in parallel in the two populations; OS was tested hierarchically.

Results

Of 1301 enrolled pts, ∼25% received NACT. At the data cut-off (30 Mar 2020) median follow-up was ∼20 months in both arms. There was no statistically significant PFS improvement in either the ITT population (HR 0.92 [95% CI 0.79–1.07]; median 18.4 months with pbo vs 19.5 months with atezo) or the PD-L1+ population (HR 0.80 [0.65–0.99], median 18.5 vs 20.8 months, respectively). Exploratory PFS analyses in the PD-L1 IC ≥5% subgroup showed a trend favouring atezo. Though immature, first interim OS results did not show significant benefit from atezo. Similar proportions discontinued any study treatment for AEs (22% pbo vs 26% atezo pts). The safety profile of atezo + bev + chemotherapy was consistent with expected AEs.

Conclusions

Atezo did not significantly improve PFS in the ITT or PD-L1+ population. The combination was generally well tolerated with manageable AEs. Exploratory biomarker subgroup analyses are ongoing.

Clinical trial identification

NCT03038100.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd), funded by F Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

K.N. Moore: Advisory/Consultancy: Aravive; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Clovis; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): GSK/Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Immunogen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Mersana; Advisory/Consultancy: OncoMed/Mereo; Advisory/Consultancy: VBL Therapeutics; Advisory/Consultancy: Vavotar; Advisory/Consultancy: Tarveda; Research grant/Funding (institution): PTC Therapeutics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): OncoMed. M. Bookman: Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: AstraZeneca; Non-remunerated activity/ies, Steering Committee: Roche; Honoraria (self): AbbVie; Honoraria (self): Aravive; Honoraria (self): Mateon; Honoraria (self): Immunogen. J. Sehouli: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): PharmaMar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: GSK/Tesaro; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novocure; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Leadership role: NOGGO; Leadership role: ESGO; Leadership role: PARSGO; Leadership role: AGO; Research grant/Funding (institution): Roche Diagnostics; Research grant/Funding (institution): Medac. G. Scambia: Advisory/Consultancy: Tesaro Bio Italy S.r.l/GlaxoSmithKline; Advisory/Consultancy: Johnson & Johnson; Speaker Bureau/Expert testimony: Clovis Oncology Italy S.r.l.; Research grant/Funding (self): MSD Italia S.r.l. J. Maenpaa: Honoraria (self): AstraZeneca; Honoraria (self): Orion Pharma; Honoraria (self): Clovis; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Tesaro/GSK. L.J. Willmott: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: GSK; Honoraria (self), Speaker Bureau/Expert testimony: Merck. N. Colombo: Honoraria (self), Travel/Accommodation/Expenses: PharmaMar; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): GSK/Tesaro; Honoraria (self): Clovis; Honoraria (self): Immunogen; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Biocad; Research grant/Funding (institution): Roche. C. Aghajanian: Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Immunogen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Clovis; Honoraria (self), Advisory/Consultancy: Eisai/Merck; Honoraria (self), Advisory/Consultancy: Mersana Therapeutics; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): AstraZeneca. F. Wu: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. L. Molinero: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. V. Khor: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. Y.G. Lin: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. S. Pignata: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): GSK; Honoraria (self): Clovis; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): PharmaMar; Research grant/Funding (institution): Pfizer. All other authors have declared no conflicts of interest.

Background

ICON8 investigated the safety and efficacy of weekly dose dense chemotherapy (q1w) in patients with epithelial ovarian cancer (EOC) compared to standard three weekly chemotherapy (q3w). ICON8 had co-primary outcomes of progression free (PFS) and overall survival (OS). Mature OS and updated PFS results are reported here.

Methods

Eligible women with FIGO stage IcG3-IV EOC were randomised 1:1:1 to arm 1 standard chemotherapy (q3w carboplatin AUC5/6 + q3w paclitaxel 175mg/m²); arm 2 weekly paclitaxel (q3w carboplatin AUC5/6 + q1w paclitaxel 80mg/m²); arm 3 weekly carboplatin-paclitaxel (q1w carboplatin AUC2 + q1w paclitaxel 80mg/m²). Patients received immediate primary surgery (IPS) prior to entering ICON8 or neo-adjuvant chemotherapy with planned delayed primary surgery (DPS) during chemotherapy. Analyses are performed on an intention to treat basis, comparing arms 2v1 and 3v1.

Results

From Jun 2011 - Nov 2014, 1566 patients were randomised, 522, 523, 521 in arms 1, 2, 3 respectively. Baseline characteristics were well-balanced – median age 62 years; serous histology 72%; stage Ic-II 19%, IIIa-IIIb 10%, IIIc-IV 72%. 48% patients had IPS, 50% planned DPS and 2% inoperable. At 1^st Oct 2019, 923 deaths had been reported, arm 1 319 (61%); arm 2 300 (57%); arm 3 304 (58%). No significant improvement in OS was observed in either comparison: arm 2v1 log rank p=0.14, hazard ratio (HR) = 0.88 (97.5% confidence interval (CI) 0.74, 1.06); arm 3v1 log rank p=0.27, HR = 0.91 (97.5% CI 0.76, 1.09). Median OS was 47.4, 54.1 and 53.4 months in arms 1, 2, 3 respectively. No heterogeneity in treatment effect was noted on subgroup analysis by surgical approach (IPS vs DPS). Updated PFS was also analysed. As in the primary analysis, no significant difference in PFS was observed with either weekly treatment (log-rank arm 2v1 p=0.37, arm 3v1 p=0.48; restricted mean PFS time 25, 25.5, 25.9 months in arms 1, 2, 3 respectively).

Conclusions

The final analysis for ICON8 confirms that, although weekly dose-dense chemotherapy is a safe alternative to q3w chemotherapy and can be delivered successfully in first-line EOC treatment, it does not significantly improve PFS or OS.

Clinical trial identification

NCT01654146; ISRCTN Registry number 10356387.

Legal entity responsible for the study

MRC Clinical Trials Unit at University College London.

Funding

Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia.

Disclosure

A.R. Clamp: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self): Clovis Oncology. I. McNeish: Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Takeda; Advisory/Consultancy: Tesaro; Research grant/Funding (institution): AstraZeneca. D.M. O'Donnell: Travel/Accommodation/Expenses: AstraZeneca. C. Coyle: Honoraria (self): Pfizer. J.D. Brenton: Advisory/Consultancy, Leadership role: Inviata; Research grant/Funding (self): Aprea; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Bayer; Advisory/Consultancy: AstraZeneca. T.J. Perren: Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: IGEA Medical. S. Sundar: Advisory/Consultancy: AstraZeneca. J.A. Ledermann: Advisory/Consultancy: Tesaro; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro. All other authors have declared no conflicts of interest.

Background

Recurrent or metastatic cervical cancer (r/mCC) is a global medical problem with few effective treatments, especially in the second- or third-line settings where available therapies have very limited activity. The phase 2 study innovaTV 204 was conducted to assess the potential of tisotumab vedotin, a tissue factor–directed antibody–drug conjugate, to address this high unmet need in patients with r/mCC.

Methods

Patients with r/mCC with disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards) and ≤2 prior systemic regimens received tisotumab vedotin 2.0 mg/kg IV once every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (cORR) as assessed by independent review committee (IRC). Secondary endpoints included duration of response (DOR), time to response (TTR), and progression-free survival (PFS) by IRC, overall survival (OS), and safety.

Results

Of 101 patients treated (median 6 doses), median age was 50 years, 68% had squamous histology, and 63% received bevacizumab plus doublet chemotherapy as first-line treatment. cORR (IRC) was 24%, including 7% with complete response (CR) (Table). Disease control rate (DCR) was 72%. At a median follow-up of 10 months the median DOR was 8.3 months, median PFS was 4.2 months, and median OS was 12.1 months. Response rates were generally consistent across subgroups explored. The most common treatment-related adverse events (TRAEs) were alopecia (38%), epistaxis (30%), and nausea (27%). Grade 3 ocular, bleeding, and peripheral neuropathy TRAEs (prespecified adverse events of interest) occurred in 2%, 2%, and 7% of patients, respectively. Table: LBA32

Antitumor activity of tisotumab vedotin in patients with r/mCC

Conclusions

Tisotumab vedotin demonstrated durable, clinically meaningful activity in a broad patient population, with a manageable and tolerable safety profile. Tisotumab vedotin has the potential to be a new therapy for patients with r/mCC.

Clinical trial identification

NCT03438396.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Nicholas Gast, PharmD, of ApotheCom (Boston, MA, USA). This assistance was funded by Genmab A/S.

Legal entity responsible for the study

Genmab A/S.

Funding

Genmab A/S.

Disclosure

R.L. Coleman: Honoraria (self): AbbVie; Honoraria (self): Aravive; Honoraria (self): Curio Science; Honoraria (self): Geistlich; Honoraria (self): Genmab; Honoraria (self): MoreHealth; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Genentech; Honoraria (self): GSK; Honoraria (self), Research grant/Funding (self): Janssen; Honoraria (self), Research grant/Funding (self): Merck; Honoraria (self): Myriad; Honoraria (self): Novocure; Honoraria (self): Roche; Honoraria (self): Tarveda Therapeutics; Honoraria (self): Tempus Labs; Honoraria (self): Tesaro; Research grant/Funding (self): Clovis Oncology; Research grant/Funding (self): Genentech-Roche; Research grant/Funding (self): OncoMed Pharmaceuticals; Research grant/Funding (self): USA National Cancer Institute. D. Lorusso: Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: PharmaMar; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses, Non-remunerated activity/ies: GSK; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution): Merck; Honoraria (self): Immunogen; Honoraria (self), Speaker Bureau/Expert testimony: Clovis; Honoraria (self): Genmab; Non-remunerated activity/ies: Abbott. C. Gennigens: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. A. González-Martín: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis; Honoraria (self), Advisory/Consultancy: Pfizer/Merck; Honoraria (self), Advisory/Consultancy: Immunogen; Leadership role: GEICO (Grupo Español Investigación Cáncer de Ovario); Leadership role: ENGOT (European Network for Gynecological Oncologic Trials); Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Oncoinvent. L. Randall: Advisory/Consultancy, Travel/Accommodation/Expenses: Agenus; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses: Intuitive; Advisory/Consultancy, Travel/Accommodation/Expenses: Mersana; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Speaker Bureau/Expert testimony: GSK/Tesaro; Non-remunerated activity/ies: GOG Foundation. L. Woelber: Honoraria (self): Tesaro, Medac Oncology, Roche, MSD, AstraZeneca, GSK, Jenapharm, Teva, OmniaMed; Research grant/Funding (institution): Medac Oncology, Tesaro, Roche, MSD, Genmab; Travel/Accommodation/Expenses: Medac Oncology, Tesaro. S. Pignata: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): GSK; Honoraria (self): Clovis; Honoraria (self): PharmaMar; Honoraria (self): Incyte; Honoraria (self), Research grant/Funding (institution): Roche. A. Redondo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: PharmaMar; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Clovis; Research grant/Funding (institution): Eisai. R. Rangwala: Full/Part-time employment: Genmab. S.D. Vindeløv: Full/Part-time employment: Genmab A/S. M. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genmab. J.R. Harris: Full/Part-time employment: Genmab. L. Nicacio: Full/Part-time employment: Seattle Genetics. M.S.L. Teng: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics. M. Smith: Full/Part-time employment: Genmab. B.J. Monk: Honoraria (self), Advisory/Consultancy: AbbVie, Advaxis, Agenus, Amgen, Akeso Bio, Aravive; Honoraria (self), Advisory/Consultancy: AstraZeneca, Asymmetric Therapeutics, Boston Biomedical, ChemoCare, ChemoID, Circulogene, Clovis; Honoraria (self), Advisory/Consultancy: Conjupro, Dicepheria, Eisai, Geistlich, Genmab/Seattle Genetics, GOG Foundation; Honoraria (self), Advisory/Consultancy: Immunogen, Immunomedics, Incyte, Lovance, Janssen/J&J, Laekna Health Care; Honoraria (self), Advisory/Consultancy: Mateon, Merck, Mersana, Myriad, Nucana, Oncomed, Oncoquest, Perthera; Honoraria (self), Advisory/Consultancy: Pfizer, Precision Oncology, Puma, Regeneron, Roche/Genentech; Honoraria (self), Advisory/Consultancy: Samumed, Takeda, Tarveda, Tesaro/GSK, Vavotar Life Sciences, VBL, Vigeo; Full/Part-time employment: Arizona Oncology (US Oncology Network). I.B. Vergote: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Amgen (Europe) GmbH; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Clovis; Advisory/Consultancy: Carrick Therapeutics; Advisory/Consultancy: Debiopharm International; Advisory/Consultancy: F. Hoffman La Roche Ltd; Advisory/Consultancy, Research grant/Funding (self): Genmab; Advisory/Consultancy: GSK; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Medical University of Vienna; Advisory/Consultancy: Millennium Pharmaceuticals; Advisory/Consultancy: MSD; Advisory/Consultancy: Octimet Oncology; Advisory/Consultancy, Research grant/Funding (self): Oncoinvent; Advisory/Consultancy: PharmaMar; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Sotio; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Deciphera; Advisory/Consultancy: Verastem; Travel/Accommodation/Expenses: MSD/Merck Zurich + USA. All other authors have declared no conflicts of interest.

Background

Nivolumab, a human anti-programmed death-1 (PD-1) receptor monoclonal antibody, is effective against some cancers. A phase II trial has supported the efficacy of nivolumab in platinum-resistant ovarian cancer, but a randomized trial is required to confirm its efficacy. This multicenter, open-label, randomized, phase III study investigated the efficacy and safety of nivolumab vs gemcitabine or pegylated liposomal doxorubicin (GEM/PLD) in platinum-resistant ovarian cancer.

Methods

Patients aged ≥20 years with platinum-resistant (advanced or recurrent) ovarian cancer and no prior GEM/PLD treatment were randomized (1:1) to nivolumab (240 mg intravenously [IV], every 2 weeks) or GEM/PLD (GEM 1000 mg/m² IV for 30 minutes on days 1, 8, and 15, then every 4 weeks; or PLD 50 mg/m² IV every 4 weeks) after stratifying for histological type (clear cell carcinoma vs others) and number of prior chemotherapy regimens after diagnosis of resistance (0 or 1). Treatment continued until disease progression or unacceptable toxicity. Tumor was assessed every 8 weeks through week 48, then every 12 weeks. Primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and safety.

Results

Of 316 patients randomized, 77.8% had ≥2 prior chemotherapies and 14.2% had ECOG PS score of 1. Median OS was 10.12 (95% confidence interval [CI], 8.34-14.09) months with nivolumab (n=157) and 12.09 (95% CI, 9.26-15.34) months with GEM/PLD (n=159), with no statistically significant difference between the groups (hazard ratio [HR] 1.03, 95% CI, 0.80-1.32; P=0.808). Median PFS was 2.04 (95% CI, 1.91-2.20) months with nivolumab and 3.84 (95% CI, 3.58-4.17) months with GEM/PLD (HR 1.46; 95% CI, 1.15-1.85; P=0.002). The rate of treatment-related grade 3/4 adverse events (AEs) was 22.4% with nivolumab and 68.4% with GEM/PLD; the major AEs (all grades) with nivolumab were diarrhea (15.4%), nausea, pruritus and rash (12.2% each). There was no difference in the toxicity profile of nivolumab from that previously reported.

Conclusions

Nivolumab did not improve OS compared with GEM/PLD in patients with platinum-resistant ovarian cancer.

Clinical trial identification

JapicCTI-153004.

Editorial acknowledgement

Medical writing assistance was provided by Hana Nomura, BPharm, of ProScribe - Envision Pharma Group and was funded by Ono Pharmaceutical Co., Ltd.

Legal entity responsible for the study

Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb Company.

Funding

Ono Pharmaceutical Co., Ltd.

Disclosure

J. Hamanishi: Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Merck Sharp & Dohme; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Sumitomo Dainippon Pharma. N. Katsumata: Advisory/Consultancy: AbbVie. D. Aoki: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical; Honoraria (self), Advisory/Consultancy: Merck Sharpe Dohme; Advisory/Consultancy, Research grant/Funding (institution): Takeda Pharmaceutical; Advisory/Consultancy: Zeria Pharmaceutical. K. Fujiwara: Honoraria (self): Bayer; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Daiichi Sankyo; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Zeria Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Kaken Pharmaceutical; Research grant/Funding (institution): Oncotherapeutics; Research grant/Funding (institution): ImmunoGen. All other authors have declared no conflicts of interest.