Table 1 Objectives and endpoints of the FIRE-8 trial

1. Objectives

 1.1 Primary Objective

 ■ To compare the efficacy of treatment with trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab

 1.2 Secondary Objectives

 ■ To compare efficacy, safety and patient reported quality of life (QoL) of treatment with trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab

 1.3 Other Exploratory Objectives

 ■ Further anti-tumor treatment after discontinuation of study treatment

 1.4 Translational Research Objectives

 ■ Identification and characterization of patient subgroups with greatest or lowest benefit from respective treatment including efficacy and toxicity

2. Endpoints

 2.1 Primary Endpoints

 ■ Objective response rate (ORR) according to RECIST 1.1 (assessment at the local trial center)

 2.2 Secondary Endpoints

 Efficacy

 ■ Overall survival (OS)

 ■ Progression-free survival (PFS)

 ■ Objective response rate (ORR) according to RECIST 1.1 (assessment by central review)

 ■ Depth of response (DoR) (assessment by central review)

 ■ Early tumor shrinkage ([ETS]; assessment by central review)

 Quality of Life

 ■ QoL as assessed with the QoL questionnaire EQ-5D-5L

 Safety

 ■ Type, incidence, severity, and causal relationship to investigational medicinal products (IMPs) of non-serious adverse events (AE) and serious adverse events (SAE; severity evaluated according to CTCAE version 5.0)

 2.3 Other Exploratory Endpoints

 ■ Subsequent anti-tumor treatment lines (monotherapy and combination therapy treatment lines including medicinal products [chemotherapeutics, antibodies and targeted therapy] and investigator reported efficacy of subsequent treatment lines