Table 4 Challenges for randomization.

Time required for molecular testing

• Prolonged time interval from patient enrollment to availability of results (~3–4 weeks).

• Need for immediate intervening therapy.

Ineligibility for clinical trials

• Targeted therapy already administered as standard of care.

• Worsening PS/death.

• Laboratory abnormalities, organ insufficiency.

• Newly diagnosed brain metastases requiring immediate treatment; for most protocols, brain metastases should be stable for ≥4 weeks after completion of treatment.

• Prior infections (HBV, HCV, HIV) that may compromise patients’ participation in clinical trials due to concern about virus reactivation.

• Delayed response from prior immunotherapy.

Resources/finances

• Prolonged time to obtain financial clearance for participation in clinical trials

• Logistic challenges requiring resources to comply with protocol procedures.

• Travel, a particularly challenging requirement during the initial phase of the COVID-19 pandemic.

Patient selection

• With the revised design many patients selected to be treated with targeted therapy (Supplemental Fig. 1)