52MO - A randomized phase II trial of durvalumab and tremelIMUmab with gemcitabine or gemcitabine and cisplatin compared to gemcitabine and cisplatin in treatment-naïve patients with CHolangio- and gallbladdEr Carcinoma (IMMUCHEC)

Background

Topaz-1 was the first phase-III study demonstrating efficacy for the PD-L1 inhibitor durvalumab (D) in combination with gemcitabine (Gem) and cisplatin (Cis), and the combination has the potential to become a new first-line standard of care in biliary tract cancers (BTCs). The aim of this proof-of-concept study was to evaluate the efficacy of tremelimumab (two dosing regimens) in combination with CTx+D.

Methods

IMMUCHEC was a prospective, randomized, multi-center phase II study. Adult patients with ECOG 0-1 and histologically confirmed metastatic BTC/gallbladder cancer were eligible. The primary endpoint was objective response rate (ORR) according to RECIST1.1 criteria in patients without prior systemic palliative CTx. Secondary endpoints were overall survival (OS) progression-free survival (PFS), and safety. Exploratory analysis included pooled efficacy and safety analysis of experimental treatment arms. The trial interventions: Arm A – D 1.5g Q3W + 4x T 75 mg Q3W + gem 1000mg/m²; Arm B - D 1.5g Q3W + 4x T 75 mg Q3W + Gem 1000mg/m² + Cis 25mg/m²; Arm C – control treatment Gem + Cis; Arm D − D 1.5g, Q3W + 1x bolus T 300 mg+ Gem + Cis; Arm E − D 1.5g Q3W + Gem + Cis.

Results

In total, 138 patients were randomized in 16 German centers. The relative distribution of anatomic subgroups (extrahepatic/intrahepatic/gallbladder) between arms: A – 21.7%/47.8%/30.4%; B – 25.0%/70.0%/5.0%; C – 26.7%/73.3%/0%; D – 13.8%/69.0%/17.2%; E – 11.1%/88.9%/0%, respectively, see the table. Correlative analysis of efficacy with genetic alterations, gene expression signatures and changes of immune cell populations will be reported. Table: 52MO

IMMUCHEC trial results

Conclusions

There was not definitive evidence of T adding substantial improvement over D alone in combination with CTx in 1^st line BTC. The omission of Cis was associated with an inferior outcome. There were no new safety signals.

Clinical trial identification

NCT03473574.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

Funded by AIO-Studien-gGmbH supported by AstraZeneca.

Disclosure

A. Vogel: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Eisai, Ipsen, Incyte, PierreFabre, Lilly, Imaging Equipment Ltd (AAA), Roche, MSD, Beigene, Jiangsu Hengrui Medicines.; Financial Interests, Personal, Advisory Board: Roche, Bayer, BMS, MSD, Eisai, Ipsen, Incyte, PierreFabre, Lilly, AstraZeneca, Boston Scientific, Sirtex, Daiichi-Sankyo. S. Boeck: Financial Interests, Personal, Advisory Role: Fresenius, AstraZeneca, Servier, Incyte, Janssen-Cilag, MSD, BMS; Financial Interests, Personal, Invited Speaker: Servier, MSD. O. Waidmann: Financial Interests, Institutional, Research Grant: Merck, Else-Kröner-Fresenius-Stiftung; Financial Interests, Personal, Advisory Role: Amgen, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Merck, Serono, MSD, Novartis, Roche, Servier; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Ipsen, EISAI, BMS, MSD, Novartis, Roche; Financial Interests, Personal, Other, travel expenses: AbbVie, Bayer, BMS, Gilead, Ipsen, Medac, Merck. C. Springfeld: Financial Interests, Personal, Invited Speaker: Roche, Servier; Financial Interests, Personal, Advisory Board: MSD, Bayer, AstraZeneca, Eisai. R. Plentz: Financial Interests, Personal, Advisory Board: Servier, AstraZeneca, BMS, MSD, Ipsen, Roche, Bayer. C. Koehne: Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Amgen, BMS, AstraZeneca; Financial Interests, Personal, Other, travel expenses: Merck; Financial Interests, Personal, Advisory Board: BMS, Merck, Amgen. All other authors have declared no conflicts of interest.