- Peter Dubsky (Lucerne, CH)
- Giuseppe Curigliano (Milan, IT)
LBA4 - Sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in Asian patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC): Results from the phase III EVER-002 study
- Shusen Wang (Guangzhou, CN)
- Binghe Xu (Beijing, CN)
- FEI Ma (Zhengzhou, CN)
- Shusen Wang (Guangzhou, CN)
- Min Yan (Zhengzhou, CN)
- Wei Li (Changchun, CN)
- Joohyuk Sohn (Seoul, KR)
- Jinhai Tang (Nanjing, CN)
- Xiaojia Wang (Hangzhou, CN)
- Ying Wang (Guangzhou, CN)
- Seock-Ah Im (Seoul, KR)
- Dongdong Jiang (Shanghai, CN)
- Theresa Valdez (Miami, US)
- Yiran Zhang (Miami, US)
- Kimberly M. Komatsubara (Foster City, US)
- Wei-Pang Chung (Tainan City, TW)
Abstract
Background
Based on results from the global TROPiCS-02 study that enrolled predominantly non-Asian pts, SG has been approved in the US and Europe for pts with pretreated HR+/HER2– mBC. We report first results from the open-label, randomized, multicenter phase 3 EVER-132-002 trial, a pivotal study that assessed SG in Asian pts with endocrine-resistant, chemotherapy (chemo)-treated HR+/HER2– mBC.
Methods
Adults from China, Korea, and Taiwan with HR+/HER2– mBC and 2-4 prior lines of systemic chemo (LOT) were randomized 1:1 to SG (10 mg/kg IV on days 1 and 8; 21-day cycle) or TPC. Pts were stratified based on number of prior LOT, visceral metastasis, and prior treatment with CDK4/6 inhibitors. The primary end point was progression-free survival (PFS) per blinded independent central review (BICR; RECIST v1.1). Secondary end points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) per BICR, and safety.
Results
Pts were randomized to SG (n = 166) or TPC (n = 165); median age was 52 y, 56% and 44% received 2 and 3-4 prior LOT for metastatic disease, respectively. At median follow-up of 13.4 mo, statistically significant improvement of PFS per BICR (33% reduction in the risk of progression or death) and clinically meaningful OS benefit (36% reduction in the risk of death) with SG vs TPC was observed (Table). Additional end points and a summary of treatment-emergent adverse events (TEAEs) are shown in the table. The most common grade ≥ 3 TEAE was neutropenia (69% for SG vs 62% for TPC). aEribulin, capecitabine, gemcitabine, or vinorelbine.
Efficacy, ITT SG (n = 166) TPCa (n = 165) 6-mo rate, % (95% CI) 41 (33-49) 24 (17-32) 6-mo rate, % (95% CI) 50 (42-58) 26 (19-34) 12-mo rate, % (95% CI) 76 (68-82) 62 (54-69) 21 (15-27) 15 (10-22) 38 (31-46) 22 (16-30) 165 (100) 164 (100) Grade ≥ 3 135 (82) 114 (70) Leading to dose reduction 42 (25) 53 (32) Leading to discontinuation 5 (3) 6 (4)
Conclusions
EVER-132-002 confirmed efficacy benefit of SG in Asian pts. The safety profile of SG was generally consistent with prior global studies. The results from this pivotal study support the use of SG as a new treatment option for Asian pts with endocrine-resistant, chemo-treated HR+/HER2– mBC.
Clinical trial identification
NCT04639986.
Editorial acknowledgement
Medical writing assistance was provided by Christiane Dresch, PhD of Parexel.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
B. Xu: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer, Roche; Financial Interests, Institutional, Research Grant: Henrui. S. Wang: Financial Interests, Personal, Invited Speaker: Pfizer, Roche, AstraZeneca, Norvats; Financial Interests, Personal and Institutional, Local PI: Pfizer, AstraZeneca, Roche; Financial Interests, Personal and Institutional, Research Grant: Pfizer. J. Sohn: Financial Interests, Personal, Stocks/Shares, Immediate Family Member: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim, Seagen. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. D. Jiang, K.M. Komatsubara: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences Inc.; Financial Interests, Personal, Stocks/Shares: Gilead Sciences Inc. T. Valdez: Financial Interests, Institutional, Stocks/Shares: Gilead Sciences. Y. Zhang: Financial Interests, Personal, Full or part-time Employment, I am a full time employee at Gilead Sciences, Inc. since 01Aug2022.: Gilead Sciences, Inc.; Financial Interests, Personal, Full or part-time Employment, I was a full time employee at Amgen from 28Oct2019 to 29Jul2022.: Amgen; Financial Interests, Personal, Stocks/Shares, I own stock of Gilead Sciences, Inc.: Gilead Sciences, Inc. All other authors have declared no conflicts of interest.
54O - Safety outcomes by UGT1A1 status in the phase III TROPiCS-02 study of sacituzumab govitecan (SG) in HR+/HER2– metastatic breast cancer (mBC)
- Valerie Y. Heong (Singapore, SG)
- Frederik Marmé (Mannheim, DE)
- Hope S. Rugo (San Francisco, US)
- Sara M. Tolaney (Boston, US)
- Aditya Bardia (Boston, US)
- Peter Schmid (London, GB)
- Wendy Verret (Miami, US)
- Theresa Valdez (Miami, US)
- Hao Wang (Foster City, US)
- Javier Cortes (Barcelona, ES)
Abstract
Background
SG is a Trop-2–directed antibody-drug conjugate approved for metastatic triple-negative BC in multiple countries and pretreated HR+/HER2– mBC in the US. In TROPiCS-02, SG significantly improved progression-free survival (PFS; median, 5.5 vs 4.0 mo; HR, 0.66;
Methods
Pts with HR+/HER2– mBC who received prior taxane, endocrine therapy, CDK4/6 inhibitor, and 2-4 prior chemotherapies (CT) were randomized 1:1 to SG or TPC. The primary endpoint was PFS by central review per RECIST 1.1; secondary endpoints included OS and safety. A post-hoc safety analysis was performed by
Results
Of 543 enrolled pts (median number of prior CT for mBC, 3; visceral metastases, 95%), 517 (SG, n=268; TPC, n=249) received ≥1 dose of study treatment.
Conclusions
SG had a manageable safety profile consistent with previous reports and across
Clinical trial identification
NCT03901339.
Editorial acknowledgement
Medical writing and editorial support was provided by Ben Labbe, PhD of Parexel.
Legal entity responsible for the study
The study is sponsored by Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
V.Y.M. Heong: Financial Interests, Institutional, Advisory Board: DKSH, Novartis, AstraZeneca, MSD; Financial Interests, Institutional, Principal Investigator: Gilead. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Seagen, Gilead/immunomedics, Eisai, PharmaMar, Genomic Health, Myriad; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Local PI: Roche, Novartis, Eisai, MSD, Vaccibody, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, Gilead/Immunomedics, German Breast Group, AGO Research GmbH; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: PUMA, NAPO, Mylan, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc., GSK, Sermonix Pharmaceuticals Ins., Pionyr Immunotherapeutics, Taiho Oncology, Inc., Veru Inc; Financial Interests, Institutional, Coordinating PI: OBI Pharma, Astellas Pharma Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Personal, Other, Travel support to academic meetings: Merck, AstraZeneca, Gilead; Non-Financial Interests, Personal, Advisory Role, I advise a number of companies without compensation: various. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma, ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, SeaGen, Novartis, Sanofi; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Ellipses Pharma, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory board/consulting: Jazz Pharma; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Institutional, Funding: Odonate, Pfizer, Sanofi, SeaGen, Cyclacel, Exelixis, Bristol Myers Squibb, Eisai, Merck, Novartis; Financial Interests, Institutional, Funding, And steering committing: AstraZeneca; Financial Interests, Institutional, Funding, And steering committee: Eli Lilly; Financial Interests, Personal and Institutional, Steering Committee Member: CytomX; Financial Interests, Institutional, Funding, and steering committee: Gilead, Genentech/Roche; Financial Interests, Institutional, Local PI: Stemline/Menarini. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Coordinating PI: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.; Non-Financial Interests, Personal, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Gilead, Eisai, MSD, SeaGen, Amgen, Celgene, Lilly; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. All other authors have declared no conflicts of interest.
Invited Discussant one LBA4 and 54O
- Shaheenah Dawood (Dubai, AE)
- Shaheenah Dawood (Dubai, AE)
Q&A and discussion
- All Speakers (Lugano, CH)
- All Speakers (Lugano, CH)
LBA5 - Capivasertib (C) + fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2– advanced breast cancer (ABC): Phase III CAPItello-291 trial Chinese cohort
- Xichun Hu (Shanghai, CN)
- Xichun Hu (Shanghai, CN)
- Qingyuan Zhang (Harbin, CN)
- Tao Sun (Shenyang, CN)
- Huihua Xiong (Chibi City, CN)
- Wei Li (Changchun, CN)
- Yuee Teng (Shenyang, CN)
- Yen-Shen Lu (Taipei City, TW)
- Ling-Ming Tseng (Taipei City, TW)
- Min Yan (Zhengzhou, CN)
- Hongsheng Li (Guangzhou, CN)
- Danmei Pang (Foshan, CN)
- Shin Cheh Chen (Taipei City, TW)
- Wenyan Chen (Nanchang, CN)
- Ou Jiang (Sichuan, CN)
- Jingfen Wang (Linyi, CN)
- Xinhong Wu (Wuhan, CN)
- Ethan Fan (Shanghai, CN)
- Lin Jiang (Shanghai, CN)
- Xiaoling Zeng (Shanghai, CN)
- Nicholas Turner (London, GB)
Abstract
Background
The global phase 3 CAPItello-291 trial of AI-resistant, HR+/HER2– ABC, C (a potent pan-AKT inhibitor) + F showed significant, clinically meaningful improvement in the dual primary endpoints of PFS in the overall and
Methods
Pts were randomised 1:1 to F (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with P or C (400 mg BID; 4 days on, 3 days off) using the same entry criteria as the global study.
Results
134 pts from mainland China (n=118) and NMPA-certified sites in Taiwan (n=16) (C + F n=71, P + F n=63) were enrolled; 34.3% had
Conclusions
Similar to the Global population, the benefit–risk profile of C + F in the Chinese cohort appears favourable; no new safety concerns with C + F were identified.
Clinical trial identification
NCT04305496.
Editorial acknowledgement
Medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc.
Legal entity responsible for the study
Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).
Funding
AstraZeneca.
Disclosure
Y. Lu: Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, MSD, Roche, Pfizer, AstraZeneca, Eisai, Daiichi Sankyo, Gilead; Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, MSD, Roche, Pfizer, AstraZeneca, Eisai, Daiichi Sankyo, Gilead; Financial Interests, Institutional, Local PI: Novartis, Roche, Pfizer, MSD, Eli Lily, Eisai, AstraZeneca, Gilead, Jellox; Non-Financial Interests, Personal, Leadership Role, Chair or co-chair of steering committee of clinical trials: Novartis; Non-Financial Interests, Personal, Advisory Role: AstraZeneca. E. Fan, L. Jiang, X. Zeng: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. N. Turner: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Roche/Genentech, GlaxoSmithKline, Zentalis pharmaceuticals, Repare therapeutics, GlaxoSmithKline, Relay therapeutics, Gilead, Inivata, Guardant, Exact Sciences; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Invitae, Inivata, Personalis, Natera; Financial Interests, Institutional, Other, provision of materials: BioRad; Financial Interests, Institutional, Other, Provision of assays: Guardant Health. All other authors have declared no conflicts of interest.
55O - Phase I study of H3B-6545 in patients (pts) with estrogen receptor-positive (ER+) breast cancer
- Makiko Ono (Koto-ku, JP)
- Makiko Ono (Koto-ku, JP)
- Takahiro Kogawa (Koto-ku, JP)
- Shigehisa Kitano (Koto-ku, JP)
- Tatsunori Shimoi (Chuo-ku, JP)
- Kasumi Yamamoto (Kashiwa, JP)
- Shingo Kobayashi (Nagoya, JP)
- Yoshiko Ichikawa (Nagoya, JP)
- Kohei Yamaguchi (Nagoya, JP)
- Yohei Otake (Nagoya, JP)
- Seiichiro Hojo (Nagoya, JP)
- Kan Yonemori (Chuo-ku, JP)
Abstract
Background
H3B-6545 is a novel selective ERα covalent antagonist. This phase 1 study (NCT04568902) evaluated the efficacy, tolerability/safety, and pharmacokinetics (PK) of H3B-6545 up to 450 mg in Japanese women with ER+, human epidermal growth factor receptor 2 (HER2)-negative, advanced/metastatic breast cancer (mBC).
Methods
This study consisted of dose escalation (DE) followed by cohort expansion (CE). In the DE part, 2 dose levels, 300 and 450 mg once daily (QD), were evaluated in a 3+3 design. In the CE, the prophylactic effect of oral antihistamine (AH; administered in the first 28 days) on rash from H3B-6545 was evaluated.
Results
Thirty-three pts were enrolled to receive H3B-6545 (DE: 300 mg, n=3; 450 mg, n=6; CE: 450 mg without prophylactic AH, n=9; 450 mg with prophylactic AH, n=15). Median age was 57 years. Median number of prior therapies for mBC was 3, including fulvestrant (79%), CDK4/6 inhibitors (73%), and chemotherapies (42%). As of 16 March 2023, 3 pts had treatment ongoing. The primary reason for treatment discontinuation was disease progression (76%). No dose-limiting toxicities (DLTs) were observed with H3B-6545 300 mg; 1 DLT (Grade 3 electrocardiogram QT-corrected- interval prolonged [QT pro]) occurred in the H3B-6545 450 mg cohort of the DE part. Overall, the most common adverse events (AEs) were sinus bradycardia (94%), anemia (61%), and QT pro (55%). The most common grade 3 AEs were anemia (15%), QT pro (12%), and rash maculopapular (12%). No grade 4 or 5 AEs were reported. Rash maculopapular or rash occurred in 10/15 pts (67%) given H3B-6545 450 mg QD with prophylactic AH and in 4/15 pts (27%) not given prophylactic AH. AEs leading to drug discontinuation occurred in 3/33 pts (9.1%); most AEs were well managed through monitoring, dose modifications and supportive care. Plasma concentration of H3B-6545 increased in a dose-dependent manner, with no substantial changes in PK profiles between cycle 1 day 1 and day 15. Among 33 pts, 1 pt had a partial response (PR) and 19 had stable disease (SD). Clinical benefit rate (CR + PR + durable SD ≥23 weeks) was 33%. Among 6 pts with ESR1 Y537S, CBR was 83% with 1 PR.
Conclusions
H3B-6545 450 mg QD had a manageable safety profile and showed preliminary antitumor effect in pts with heavily pretreated, ER+, HER2-negative mBC.
Clinical trial identification
NCT04568902.
Editorial acknowledgement
Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA.
Legal entity responsible for the study
Eisai Inc., Nutley, NJ, USA.
Funding
Eisai Inc., Nutley, NJ, USA.
Disclosure
M. Ono: Financial Interests, Personal, Speaker’s Bureau: Chugai, Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Principal Investigator: Astellas, Eisai. T. Kogawa: Financial Interests, Personal, Invited Speaker: Eli Lilly, AstraZeneca, Taiho, Eisai, Pfizer, Daiichi Sankyo, Chugai; Financial Interests, Institutional, Research Grant: Eli Lilly, Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Eisai, AstraZeneca; Financial Interests, Personal, Advisory Role: Eli Lilly, Daiichi Sankyo, Onco Therapy Science. S. Kitano: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Bristol Myers Squibb, Chugai, Eisai, GSK, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Taiho, Takeda; Non-Financial Interests, Personal, Advisory Board, Scientific Advisor: ImmuniT Research; Non-Financial Interests, Personal, Other, Lecture fee, Scientific adviser: Ono Pharmaceutical Co., Ltd.; Non-Financial Interests, Personal, Expert Testimony: PMDA(Pharmaceuticals and Medical Devices Agency); Financial Interests, Personal, Advisory Board, Scientific advisor: Rakuten Medical, Sumitomo Pharma, United Immunity; Financial Interests, Personal and Institutional, Local PI, Clinical Trial: AbbVie, Astellas, AstraZeneca, Eisai, Eli Lilly Japan K.K., GSK, Incyte, LOXO Oncology, MSD, Pfizer, Takeda; Financial Interests, Personal and Institutional, Local PI, Clinical Trial, Research Grant: Chugai, Daiichi Sankyo; Financial Interests, Personal and Institutional, Local PI, Clinical trial, Research Grant: Nippon Boehringer Ingelheim; Financial Interests, Personal and Institutional, Coordinating PI, Clinical trial, Research Grant: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant, Clinical trial, Research Grant: Takara Bio Inc. S. Kobayashi,Y. Ichikawa, K. Yamaguchi, Y. Otake, S. Hojo: Financial Interests, Personal, Full or part-time Employment: Eisai Co. Ltd. K. Yonemori: Financial Interests, Personal, Invited Speaker, Honorarim for lecture: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR pharma, MSD, Boehringer Ingelheim, Ono, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncXerna, Takeda, Novartis, MSD; Financial Interests, Institutional, Research Grant: MSD, Daiichi Sankyo, Merk Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe; Financial Interests, Institutional, Principal Investigator: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Merk Biopharma, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. All other authors have declared no conflicts of interest.
Invited Discussant one LBA5 and 55O
- Soo Chin Lee (Singapore, SG)
- Soo Chin Lee (Singapore, SG)
Q&A and discussion
- All Speakers (Lugano, CH)
- All Speakers (Lugano, CH)