SOCRA 2024 Annual Conference Program Book - Flipbook - Page 59
Flexibility: Cohorts
Dose Randomization
Multiple cohorts:
Target sensitivity:
KRAS G12D vs G13D
Histological: BRAFi in CRC vs melanoma
Sanctuary sites: brain mets
Organ dysfunction: liver, renal
Target drug exposure (if high
interpatient variability)
Backfilling cohorts (specially in DL where
activity has been seen)
Jiang et al. Can Discovery 2024
Araujo et al. Ann Oncol 2022
Recommended dose range (RDR) rather than MTD
Intrapatient dose escalation
Additional PK sampling to inform dose‐
Still benefit to determine MTD
exposure curve
Understand consequences of altered
For patients enrolled at dose level (DL) where
drug exposures
activity not seen
Explore toxicity‐dosage relationships
After higher DL deemed tolerable
Higher doses may be needed in:
Higher DL with different PK
Brain metastases
For patients with stable disease
High drug clearance
How about patients with progression?
Define scenarios
Less sensitive mutations
Data released by Revolution Medicine 7/15/2024
Araujo et al. Ann Oncol 2022
Multiple recommended doses
Serial tumor biopsies
Routine use discouraged
Tumor types
Morbidity
Interaction TME (PDAC‐
Provide limited information
desmoplastic barrier)
Replaced by:
Molecular alteration
Liquid biopsies: ctDNA (VAF clearance)
PanRas inhibitors (G12 vs other)
Molecular imaging and theranostics
GIST exon 9 vs 11 (800 vs 400mg)
Consider if
Sanctuary sites of disease
Non‐invasive procedures are inadequate
Validated biomarkers, defined statistical
plan
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