Table 1 Details and objectives of the experiments conducted

Experiment #1: target engagement after SAR439859 single injection

FES-PET 4 h post-therapy

Single SAR439859 administration; doses tested: 1.25, 5, 12.5 mg/kg

Measure dose effect on [¹⁸F]-FES tumor uptake after a single administration of SAR439859 over 1.25–12.5 mg/kg range of doses

Experiment #2: target engagement after SAR439859 repeated injections

FES-PET (baseline vs post-therapy)

4 days SAR439859 treatment:

- 5 mg/kg, bid

- 12.5 mg/kg, bid

- 25 mg/kg, qd

Measure target engagement after repeated SAR439859 treatments over 5–25 mg/kg range of doses, correlate target engagement with IHC, compare dose regimens

Experiment #3: tumor metabolism evaluation under SAR439859 treatment

FDG-PET (baseline vs under treatment at 18 h and 42 h after start of therapy)

FES-PET (post-therapy to confirm target engagement)

3 days treatment:

- SAR439859 5 mg/kg, bid

- Palbociclib 100 mg/kg, qd

- Combination

Measure tumor metabolism under SAR439859 as single agent or in combination with palbociclib

Experiment #4: tumor proliferation evaluation post SAR439859 treatment

FLT-PET (baseline vs post-therapy)

FES-PET (post-therapy to confirm target engagement)

4 days treatment:

- SAR439859 5 mg/kg, bid

- Palbociclib 100 mg/kg, qd

- Combination

Measure tumor proliferation after 4 days of SAR439859 treatment as single agent or in combination with palbociclib