101P - Quality of life (QoL) outcomes in patients (pts) with zanidatamab (zani)-treated HER2-positive (HER2+) biliary tract cancer (BTC) in the phase IIb HERIZON-BTC-01 study

Background

In the pivotal HERIZON-BTC-01 study, the HER2 bispecific antibody zani demonstrated rapid, durable responses (confirmed objective response rate, 41% by independent central review; median duration of response, 12.9 mo; data cut-off: Oct 2022) and manageable safety in pts with HER2+ BTC. Here we report QoL outcomes for those pts with HER2+ BTC.

Methods

HERIZON-BTC-01 (NCT04466891), an ongoing open-label, global phase 2b study, evaluated zani (20 mg/kg IV every 2 wks) in pts with HER2+ (gene amplification with immunohistochemistry of 2+ or 3+), locally advanced, unresectable or metastatic BTC (gallbladder cancer, intra-/extra-hepatic cholangiocarcinoma) who received prior gemcitabine-containing treatment (tx). QoL, an exploratory endpoint, was assessed using the EQ-5D-5L descriptive system and visual analogue scale (VAS) at baseline (BL) and every 8 wks; best on-treatment score (BONT) was the lowest descriptive or highest VAS value observed post-BL.

Results

A total of 80 pts with HER2+ BTC were evaluated for primary efficacy analyses (median age, 64 years; 56% female). Of these, 1 (1%) had complete response (CR), 32 (40%) had partial response (PR), 22 (28%) had stable disease (SD) and 24 (30%) had progressive disease (PD); 1 pt was not evaluable. Pts with CR or PR reported the greatest improvement in QoL followed by those with SD, while pts with PD generally reported worsening QoL (Table). Median VAS scores improved by ≥10 points from BL to time of BONT for pts with CR and PR, by 5 points for pts with SD and worsened by 10 points for pts with PD. In each dimension, the proportion of pts reporting ‘no problem’ increased more from BL to BONT for pts with PR than for pts with SD or PD. Table: 101P

EQ-5D-5L QoL outcomes in pts with HER2+ BTC by tumour response

^aOut of pts with a BL and ≥1 post-BL score

Conclusions

In HERIZON-BTC-01, pts with HER2+ BTC who responded to zani reported improved QoL compared with BL, while those with PD reported worsening QoL compared with BL. These results support the continuing development of zani as a HER2+ BTC tx option.

Clinical trial identification

NCT04466891, first posted July 10, 2020.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Tara Suntoke, of CMC AFFINITY, a division of IPG Health Medical Communications, with funding from Jazz Pharmaceuticals, in accordance with Good Publication Practice (GPP 2022) guidelines.

Legal entity responsible for the study

Jazz Pharmaceuticals, Zymeworks BC Inc., and BeiGene Ltd.

Funding

Pharmaceutical/biotech: Jazz Pharmaceuticals, Zymeworks BC Inc., and BeiGene Ltd.

Disclosure

H.S. Wasan: Financial Interests, Personal, Advisory Board, Advisory Boards and Invited Speaker: Incyte, Pierre Fabre, Servier, Bayer, Roche/Genentech/ FM AG, Sirtex Medical Erytech, Celgene, Array BioPharma, Merck KGaA: BMS; Financial Interests, Personal, Steering Committee Member, Trial steering committee and advisory: Zymeworks; Financial Interests, Personal and Institutional, Coordinating PI, Trial PI steering committee and advisory: Sirtex Medical; Financial Interests, Personal, Other, Consultancy for Submission for UK approval (BSI): ONCOSL; Non-Financial Interests, Advisory Role, Trial steering committee: Pfizer; Non-Financial Interests, Advisory Role, UK NICE submission: Bayer, Pierre Fabre. J.J. Harding: Financial Interests, Personal, Advisory Board: Adaptimmune, Bristol Myer Squib, CytoMx, Eisai, Exelexis, Elevar, Hepion, Eli Lilly, AstraZeneca, Medivir, QED, Sevier, Merck. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono , Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. H. Chang: Financial Interests, Institutional, Local PI: BeiGene, Ltd., Senhwa biosciences, Taiho Oncology, Astellas Pharma Global Development, AbbVie. H. Sun: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Roche, MSD, Hengrui, TopAlliance, Innovent, Bayer; Non-Financial Interests, Institutional, Local PI: AstraZeneca, Eisai, Roche, MSD, Hengrui, Innovent. T. Macarulla: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd, Celgene SLU, Eisai, IPSEN Pharma, Incyte; Financial Interests, Personal, Other, Direct research fund: Servier, Merck, Sharp and Dhome, Novocure, QED Therapeutics Inc, Roche, Sanofi-Aventis, Zymeworks; Financial Interests, Personal, Invited Speaker: Lilly, Janssen; Financial Interests, Institutional, Research Grant: Amc Medical Research, Armo Biosciences, Basilea, Biokeralty Research Institute, Merck Sharp & Dohme, Oncomed Pharmaceuticals, QED Therapeutics, VCN Biosciences, AbbVie Farmaceútica, Ability Pharmaceuticals, Agios, Amgen, Aslan, AstraZecena, Bayer, BeiGene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, Fibrogen, Genentech, Hallozyme, Immunomedics, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, Medimmune, Merimarck, Millenim, Nelum, Novartis, Novocure, Pfizer, Pharmacyclics, Roche, Zymeworks; Non-Financial Interests, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO. J. Metges: Financial Interests, Personal, Expert Testimony: Astellas, MSD; Financial Interests, Personal, Invited Speaker: BMS, MSD, Daiichi. J.A. Bridgewater: Financial Interests, Personal, Advisory Board: Taiho, BMS, Incyte, Basilea, Servier; Financial Interests, Institutional, Funding: Incyte. E.Y. Chen: Non-Financial Interests, Institutional, Research Funding: Taiho Oncology, Inc.; Non-Financial Interests, Personal and Institutional, Invited Speaker: Horizon CME. M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Pierre Fabre, Merck Kga, Pfizer, Bayer, Lilly, Servier; Financial Interests, Personal, Advisory Board: Roche, Basilea, Sotio, Pierre Fabre, Bohringer, Rafael, Servier, Zymeworks, Ipsen, Bayer, HalioDX, Lilly, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of bevacizumab in NET: Roche; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of steptozotocin in NET: Keocyt; Financial Interests, Institutional, Local PI: Rafael, Amgen; Financial Interests, Institutional, Funding: Bayer; Other, My wife is head of the oncology business unit in the French Affiliate of Sandoz: Sandoz France. J. Ma: Financial Interests, Personal, Full or part-time Employment: BeiGene.Ltd. P. Garfin: Financial Interests, Personal, Full or part-time Employment, Also own equity: Zymeworks; Financial Interests, Personal, Stocks or ownership: Seage. S. Pant: Financial Interests, Personal, Advisory Role: Zymeworks, Ipsen, Novartis, Janssen, Boehringer Ingelheim, AskGene Pharma; Financial Interests, Institutional, Research Funding: Mirati Therapeutics, Lilly, Xencor, Novartis, Rgenix, Bristol Myers Squibb, Astellas Pharma, Framewave, 4D Pharma, Boehringer Ingelheim, NGM Biopharmaceuticals, Janssen, Arcus Biosciences, Elicio Therapeutics, bionte, Ipsen, Zymeworks, Pfizer, ImmunoMET, Immuneering, Amal Therapeutics. All other authors have declared no conflicts of interest.