Abstract 738P
Background
Cancer of unknown primary (CUP) has a dismal prognosis. Second-line therapy following progression to platinum-based treatment leads to response rates of 0-19% and a median progression-free survival (PFS) of only 2-4 months. 10-23% of CUP patients demonstrate a high tumor mutational burden (TMB), which predicts response to immunotherapy across several cancer types.
Methods
After failure of platinum-based therapy, patients were stratified based on TMB (high vs low) and treated with combined ipilimumab (1 mg/kg every 6 weeks) and nivolumab (240 mg biweekly). PFS was the primary and overall survival, overall response rate (ORR), duration of clinical benefit and safety objectives secondary endpoints. Serial plasma samples were analysed regarding circulating cell-free (cfDNA) and tumor DNA (ctDNA) to determine the role of combined capture-based targeted and shallow whole genome sequencing in monitoring response to treatment.
Results
31 patients were enrolled into the study. 52% had adenocarcinomas and 32% squamous cell or undifferentiated carcinomas. High TMB (>12 mutations/Mb) was found in 16% of patients. Two patients achieved complete (6.5%) and three partial remissions (9.7%) according to RECIST v1.1, resulting in an ORR of 16.2%. Stable or progressive disease was found in one (3.2%) and twelve cases (38.7%) respectively, while 13 additional patients suffered rapid clinical progression already before first response assessment. Three of five patients (60%) with high TMB and two of 26 patients (7.7%) with low TMB reached an objective response. CUP patients (N=35) showed significantly higher cfDNA concentrations compared to healthy controls (N=19) (median 5.5 vs 1.7 ng/ml plasma; p<0.0001), with a wide range (0.9-300.9 ng/ml plasma) that correlated positively with tumor burden and negatively with treatment response.
Conclusions
First results of the CheCUP trial demonstrate an ORR of 16% to combined ipilimumab/nivolumab in patients relapsed or refractory to platinum-based chemotherapy. Final results for all 31 patients including safety and ctDNA sequencing data will be available upon presentation.
Clinical trial identification
EudraCT 2018-004562-33.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BMS.
Disclosure
M. Stahl: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche. H. Löffler: Financial Interests, Institutional, Sponsor/Funding: Almac Diagnostics, Icon, Bayer Vital GmbH, OnkoDataMed, Alcedis, IOMedico, Quintiles GmbH, ClinAssess, AstraZeneca, IKF GmbH am Krankenhaus Nordwest, Biontech; Non-Financial Interests, Personal, Member: DGHO, Deutsche Krebsgesellschaft, AIO der Deutschen Krebsgesellschaft. U.T. Hacker: Financial Interests, Personal, Invited Speaker: Roche, Servier, Novartis, Merck Serono; Financial Interests, Institutional, Research Grant: Celgene, Roche Diagnostics. C.B. Westphalen: Financial Interests, Personal, Invited Speaker: Bayer, BMS, Celgene, GSK, Roche, Servier, Sirtex, Taiho, Chugai, Amgen, Falk, MSD, Merck, Janssen; Financial Interests, Personal, Advisory Board: BMS, Celgene, Shire/Baxalta, Rafael, RedHill, Roche; Financial Interests, Personal, Other, Travel Support: Bayer, Celgene, RedHill, Roche, Servier, Taiho; Financial Interests, Personal, Expert Testimony: Janssen; Financial Interests, Personal and Institutional, Research Grant: Roche; Non-Financial Interests, Officer: AIO - Arbeitsgemeinschaft Internistische Onkologie (Germany). M. Bitzer: Financial Interests, Personal, Advisory Board: Roche Pharma AG, Incyte Biosciences, Bayer Vital, BMS, MSD Sharp & Dome, Ipsen; Financial Interests, Personal and Institutional, Principal Investigator: Incyte, Bayer, MSD, BMS, Ipsen, QED Therapeutics, Roche; Non-Financial Interests, Personal, Writing Engagements: German Society of Gastroenterology, Digestive and Metabolic Diseases. A. Stenzinger: Financial Interests, Personal, Honoraria: AstraZeneca, AGCT, Bayer, BMS, Eli Lilly, Illumina, Janssen, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda, Thermo Fisher; Financial Interests, Personal, Research Grant: Bayer, BMS, Chugai, Incyte. T. Bochtler: Financial Interests, Institutional, Other: Roche; Non-Financial Interests, Personal, Invited Speaker: Pfizer; Non-Financial Interests, Personal, Member: Deutsche Krebsgesellschaft. A. Krämer: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Sponsor/Funding: BMS, Molecular Health; Financial Interests, Personal and Institutional, Principal Investigator: Roche; Non-Financial Interests, Personal, Member: DGHO, ESMO, AIO, DKG. All other authors have declared no conflicts of interest.