133O - Safety of 30 min infusion of durvalumab (D) in combination with gemcitabine (G)-based chemotherapy in first-line treatment (tx) of advanced biliary tract cancer (aBTC): TOURMALINE early results

Background

The global, single-arm, Phase 3b TOURMALINE study (NCT05771480) assesses the safety and efficacy of D + G-based chemotherapy as first-line tx in aBTC. Optimising care by reducing infusion time may benefit patients and physicians. Preliminary safety data, including 30 min infusion time with D are reported.

Methods

Participants (pts) received D 1500 mg (first infusion: 60 min; subsequent infusions: 30 min) with an investigator-selected G-based chemotherapy (D + G alone or in combination with oxaliplatin, carboplatin, cisplatin (cis), tegafur-gimeracil-oteracil (S-1), cis + S-1, or cis + nab-paclitaxel). D was administered every 3 weeks (Q3W) with a G-based chemotherapy Q3W (8 cycles of D) or Q4W with G + cis + S-1 Q2W (4 cycles of D). Data cut-off (DCO) for the predefined safety review was 27 March 2024.

Results

Overall, 62 pts could have received ≥2 cycles of D by DCO. Over 90% of pts were Asian with a median age of 66 years; 23% had locally advanced disease, 61% had metastatic disease and 16% had both. At screening, 24% of pts had ECOG PS 2, reflecting pts with more severe disease versus the TOPAZ-1 study (NCT03875235). Safety was comparable between 60 and 30 min D infusion time. One pt had an infusion reaction adverse event (AE) at Cycle 4 following D + G + oxaliplatin (possibly related to oxaliplatin). AEs and serious AEs (SAEs) were reported in 98% and 29% of pts, respectively, and 87% and 6% of pts had an AE or SAE possibly related to any study tx, respectively (Table). Grade 3 or 4 AEs and SAEs were reported in 68% and 24% of pts, respectively. AEs led to a D dose delay in 26% of pts and discontinuation in 2% of pts. Immune-related AEs (imAEs) occurred in 29% of pts (Table). There were no AEs with an outcome of death Table: 133O

^∗Investigator assessed. Missing responses counted as related. ^†ECOG PS 2 pts only.PR, possibly related to any study tx.

Conclusions

No difference in infusion-related safety between 30 and 60 min infusion time was observed. No new safety signals were seen with the addition of D to other chemotherapy regimens beyond TOPAZ-1 regimens.

Clinical trial identification

NCT05771480.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Victoria Harle, PhD, on behalf of CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

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, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience, Alligator Bioscience AB; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai, Nihon Servier, Novartis, Bristol Myers Squibb, MSD, Boehringer Ingelheim, Astellas Pharma, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Fujifilm Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan, Nobelpharma, EA Pharma; Financial Interests, Institutional, Coordinating PI: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V., Merck biopharma, Boehringer Ingelheim, Invitae, Nobelpharma; Financial Interests, Personal, Steering Committee Member: Chugai, Nihon Servier, Takeda, Novartis, Eisai, Rakuten Medical. A.R. He: Financial Interests, Personal, Invited Speaker, Speaker's Bureau: Eisai; Financial Interests, Personal, Invited Speaker, Speaker's bureau: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. T. Macarulla Mercade: 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, Personal, Member: American Society of Clinical Oncology - ASCO, “Sociedad Española de Oncología Médica” – SEOM, Sociedad Europea de Oncología Médica - ESMO; Other, Personal, Other, Editorial Board: GI Annals og¡f Oncology. A. Dane: Financial Interests, Institutional, Other, Consultant: Adagio, Amplyx, AN2, Bioscript, Bugworks, CARBX, Closed Loop Medicine, Correvio, Davolterra, Destiny, Evopoint, F2G, Entasis, Gates, GSK, Humanigen, Liverpool University, Kymab, Melinta, Modis, Orca, Phico, Quince, Roche, SFunga, Scynexis, Sinovent, SNIPR; Financial Interests, Institutional, Other, Independent statistician on DSMBs: Aridis, Cerium, ContraFect, Egetis, Midatech, Pfizer, Pled, Rare Thyroid, Sanofi, Transcrip. J.O. Park: Financial Interests, Personal, Advisory Board: MedPacto, BMS (Celgene), Servier, MediRama, Adicet Bio, AstraZeneca, Merck Sereno, ImmuneOncia, Merck; Financial Interests, Personal, Other, Travel support for a poster presentation at ASCO GI 2023: Minneamrita Therapeutics LLC; Financial Interests, Personal, Research Grant, Clinical research grant: MedPacto, Servier, BMS (Celgene); Financial Interests, Personal, Research Grant: Eutilex, ABL Bio. F. Dayyani: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca; Financial Interests, Personal, Invited Speaker: Ipsen, Sirtex, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Bayer, Roche, Ipsen, Merck; Financial Interests, Institutional, Coordinating PI: Exelixis, Signatera, Taiho. G. Wetherill: Financial Interests, Personal, Other, Contracted employee: AstraZeneca. A. Stell, B. Baur, P. Sun: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Mannheim, Eisai, Incyte, Ipsen, MSD, Roche, Servier, Tyra, Tahio, AbbVie; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, MSD, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Roche, MSD, Beigene, Boehringer-Ingelheim.