Abstract
What is this summary about?
Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified. Zanidatamab is an antibody designed to destroy cancer cells that have higher-than-normal HER2 protein or gene levels. Zanidatamab is currently under research and is not yet approved for any diseases. Participants in this phase 2b clinical study had tumors that were HER2-amplified and at the advanced or metastatic stage. Participants also had cancer which had become worse after previous chemotherapy or had side effects that were too bad to continue chemotherapy. They also had to meet other requirements to be enrolled. Researchers measured the amount of HER2 protein in the tumor samples of the participants who were enrolled. There were 80 participants with tumors that were both HER2 amplified and had higher-than-normal HER2 protein amounts (considered to be ‘HER2-positive’). There were 7 participants with tumors that were HER2-amplified, but had little-to-no levels of the HER2 protein (considered to be ‘HER2-low’). All participants in the study were treated with zanidatamab and no other cancer treatments once every 2 weeks.
What are the key takeaways?
In the HER2-positive group, 33 of 80 (41%) participants had their tumors shrink by 30% or more of their original size. In half of these participants, their tumors did not grow for 13 months or longer. No participant in the HER2-low group had their tumors shrink by 30% or more. In total, 63 of 87 participants (72%) had at least one side effect believed to be related to zanidatamab treatment. Most side effects were mild or moderate in severity. No participant died from complications related to zanidatamab. Diarrhea was one of the more common side effects and was experienced by 32 of 87 participants (37%). Side effects related to receiving zanidatamab through the vein, such as chills, fever, or high blood pressure, were experienced by 29 of 87 participants (33%).
What are the conclusions reported by the researchers?
The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.
Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study)
TWEETABLE ABSTRACT
The HERIZON-BTC-01 study revealed zanidatamab as a potentially effective treatment for HER2-positive biliary tract cancer after standard chemotherapy fails. Read more in the lay summary by @hardingjjmd, @DrShubhamPant, and coauthors. #BiliaryTractCancer #HER2 #zanidatamab
Keywords: :
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Financial disclosure
JJ Harding has received funding from Bristol Myers Squibb, Boehringer Ingelheim, CytomX, Debiopharm, Eli Lilly, Genoscience, Incyte, Loxo@Lilly, Novartis, Polaris, Pfizer, Yiviva, and Zymeworks (uncompensated). DY Oh has received funding from Array, AstraZeneca, BeiGene, Eli Lilly, Handok, Merck Sharp & Dohme, Novartis, and Servier. JW Kim has received funding from Inno.N and Jeil Pharm. HM Chang has received funding from Zymeworks. HC Sun has received payments or honoraria from AstraZeneca and TopAlliance. T Macarulla has received speaker's fees from Janssen and Lilly; and has received direct research funding from Merck Sharp & Dohme, Novocure, QED Therapeutics, Roche Farma, Sanofi-Aventis, Servier, and Zymeworks. JP Metges has received honoraria from Astellas Pharma, Bayer, Bristol Myers Squibb, Merck, and Merck Sharp & Dohme. J Bridgewater has received funding from Incyte and has received honoraria from Incyte and Servier. MA Tejani has received honoraria from Caris and Natera. H Wasan has received research funding from Merck Serono, Merck Sharp & Dohme, Pfizer, and SIRTEX Medical. M Ducreux has received funding from Keocyt, Merck Serono, and Roche. Y Bao and J Ma are employees of, and own stock or stock options of, BeiGene. M Bachini has consulted for, received honoraria, and served as a speaker for AstraZeneca, Boston Scientific, Compass Therapeutics, Relay Therapeutics, and Taiho. H Morement discloses the following sponsorships and grants received by AMMF – The Cholangiocarcinoma Charity: AstraZeneca, Helsinn, Incyte, Jazz Pharmaceuticals, Servier, Taiho, TransThera, and Zymeworks. L Boyken is an employee of, and owns stock or stock options of, Zymeworks. P Garfin is a former employee of, and owned stock or stock options of, Zymeworks; is an employee of, and owns stock or stock options of, Jazz Pharmaceuticals; and owns stock or stock options of Seagen. S Pant has received funding from 4D Pharma, Amal Therapeutics, Arcus Biosciences, Astellas Pharma, BioNtech, Boehringer Ingelheim, Bristol Myers Squibb/Mirati Therapeutics, Elicio Therapeutics, Framewave, Immuneering, ImmunoMET, Ipsen, Janssen, Lilly, NGM Biopharmaceuticals, Novartis, Pfizer, Rgenix, Xencor, and Zymeworks. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Writing disclosure
Medical writing support, under the direction of the authors, was provided by Ellen Woon, PhD, of CMC Affinity, a division of IPG Health Medical Communications, with funding from Jazz Pharmaceuticals, in accordance with Good Publication Practice (GPP 2022) guidelines.
Acknowledgements
The authors would like to thank all participants and their families, all investigators, clinical study researchers, personnel, and staff who contributed to or participated in the HERIZON-BTC-01 study. HERIZON-BTC-01 was conducted in accordance with the Declaration of Helsinki and International Good Clinical Practice guidelines and was overseen by an independent data monitoring committee.
Competing interests disclosure
JJ Harding has consulted or been an advisory board member for Adaptimmune, AstraZeneca, Bristol Myers Squibb, Eisai, Elevar, Exelixis, Genoscience, Hepion, Imvax, Merck, Medivir, QED, Tyra, and Zymeworks. DY Oh has been an advisory board member for Arcus Biosciences, ASLAN, AstraZeneca, Basilea, Bayer, BeiGene, Bristol Myers Squibb/Celgene, Genentech/Roche, Halozyme, IQVIA, Merck Serono, Novartis, Taiho, Turning Point, Yuhan, and Zymeworks. HJ Choi has consulted for AstraZeneca and Roche. JW Kim has consulted for AstraZeneca, BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, Merck Sharp & Dohme, ONO, Sanofi-Aventis, Servier, and TCUBEit. HC Sun has consulted for TopAlliance. T Macarulla has an advisory role at Ability Pharmaceuticals SL, AstraZeneca, Basilea Pharma, Baxter, BioLineRX Ltd., Bristol Myers Squibb/Celgene, Eisai, Incyte, and Ipsen Bioscience Inc.; and has received speaker's fees from Janssen and Lilly. J Bridgewater has consulted for Bristol Myers Squibb, Incyte, Servier, and Taiho. H Wasan is an advisory board member and/or invited speaker at Amgen, Bayer, Bristol Myers Squibb/Celgene, BTG, Erytech Pharma, Incyte, Merck KGaA, Pfizer, Pierre Fabre, Roche/Genentech/FM, Seagen, Servier, SIRTEX Medical, and Zymeworks; has consultancies at Bayer, Bristol Myers Squibb/Celgene, Incyte, NICE/BSI expert, Oncosil, and Pierre Fabre; and is a member of the Global Trials steering committee at ARCAD (Pancreas Academic), Merck KGaA, Pfizer/Array, SIRTEX Medical, and Zymeworks. M Ducreux has been an advisory board member for Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, and Servier; has been a speaker in symposia for Bayer, Daiichi Sankyo, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Roche, and Servier; and participated in independent data monitoring committees for Pancan and Roche. M Ducreux's spouse is the head of the oncology business unit at Sandoz France. S Pant has consulted for AskGene Pharma, Boehringer Ingelheim, Ipsen, Janssen, Novartis, and Zymeworks. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.