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