Comprehensive profiling and molecularly guided therapy (MGT) for carcinomas of unknown primary (CUP): CUPISCO: A phase II, randomised, multicentre study comparing targeted therapy or immunotherapy with standard platinum-based chemotherapy (2018)

Background: CUPs are heterogeneous tumours of diverse origins that often have poor prognoses and high unmet clinical need. Their heterogeneity makes the conduct of clinical trials difficult. The CUPISCO study aims to compare the overall efficacy and safety of MGT with standard platinum-based chemotherapy for patients (pts) with CUP. Trial design: Eligible pts have a histological diagnosis of adeno- or poorly differentiated carcinoma without detectable primary tumour according to ESMO diagnostic guidelines (nonspecific CUP subset per ESMO definition only); Eastern Cooperative Oncology Group performance status 0–1; ≥1 measurable lesion; and are naive to systemic therapy. All pts receive hybrid capture-based comprehensive genomic profiling (FoundationOne®, FoundationACT®) to assess tumour genomic alterations, microsatellite instability and tumour mutational burden. Pts who achieve complete response [CR], partial response [PR] or stable disease [SD] after 3 induction chemotherapy cycles of carboplatin/paclitaxel, carboplatin/gemcitabine or cisplatin/gemcitabine are randomised (3:1) to investigator’s choice (IC) from 9 MGT regimens (7 targeted therapy regimens, 2 immunotherapy regimens) or 3 further chemotherapy cycles. Randomisation is stratified by gender and response during the induction period (CR + PR vs SD). A key element of the trial design is a ‘Molecular Tumour Board (MTB)’, comprising the investigator, reference pathologist, reference oncologist and cancer genomics consultant (when needed), who advise investigators on MGT choice based on tumour genomic profiles. Pts with progressive disease during the induction period will be assigned to IC of MGT regimens with advice from the MTB. The primary efficacy endpoint is investigator-assessed progression-free survival (time from randomisation to first occurrence of disease progression per Response Evaluation Criteria in Solid Tumors v1.1, or death from any cause). Enrolment of 790 pts is planned across 23 countries and ∼101 sites. Recruitment is ongoing; 5 pts have been screened to date (NCT03498521). Clinical trial identification: NCT03498521. Editorial acknowledgement: Support for third-party writing assistance for this abstract, furnished by Blair Jarvis, MSc, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Legal entity responsible for the study: F. Hoffmann-La Roche Ltd. Funding: F. Hoffmann-La Roche Ltd. Disclosure: A. Krämer: Honoraria: Roche and Bayer; Consulting or advisory role: Roche, Bayer and Daiichi; Research funding: Bayer; Patents, royalties, other intellectual property: Bayer; Travel, accommodation and expenses: Roche. L.M. Gay: Employment: Foundation Medicine Inc.; Ownership of stock or other interests: Gilead Sciences and Foundation Medicine, Inc. D.R. Page: Employment: Roche/Genentech; Immediate family member employment: Novartis; Ownership of stock or other interests: Roche; Immediate family member ownership of stock or other interests: Novartis. S. Foser: Employment: Roche/Genentech; Ownership of stock or other interests: Roche. T.I. Mughal: Employment: Foundation Medicine, Inc.; Leadership: Foundation Medicine, Inc.; Stock or other ownership at Foundation Medicine, Inc.; Honoraria: Sanofi; Patents, royalties, other intellectual property for Oxford University Press and Informa. J.S. Ross: Employment: Foundation Medicine, Inc.; Leadership: Foundation Medicine, Inc.; Ownership of stock or other interests: Foundation Medicine Inc.; Honoraria: Pfizer and EMD Serono; Research funding: Foundation Medicine Inc. G. Baciarello: Consulting or advisory role: Janssen and Sanofi; Travel, accommodation and expenses: Janssen, Astellas, AstraZeneca and Sanofi. L.R. Mileshkin: Travel, accommodation and expenses: Roche and BeiGene. S. Osborne: Employed: Roche. H. Moch: Consulting or advisory role: Roche and Definiens; Research funding: Roche. All other authors have declared no conflicts of interest.