SOCRA 2024 Annual Conference Program Book - Flipbook - Page 57
Challenges with dose selection strategy
Recommended dose range based on totality of the data
Toxicity/Tolerability
Efficacy
Pharmacokinetics
Pharmacodynamics
Shah ESMO 2023
Optimization Scenarios
Patient population
Dose escalation
Randomized Phase 2
Heterogeneous
Homogeneous
Randomization
No > Yes
Yes
Rare oncogene addicted (ie NTRK)
Feasible
Not feasible
Stratification factors
How/When?
Dose optimization goal
No
2‐3, enough?
Backfill cohorts
Parallel dose resp trial
Disease specific expansions
Separate trial
Dose range
Optimal dose
Two case studies to show dose
optimization…
Dose optimization: pharmacodynamics
PEMIGATINIB
FIGHT‐101
In vivo models max TGI with doses that
Part 1: Dose escalation
provided > 12h coverage above 50% of
max inhib concentration
MTD not reached
Doses > 6mg provided more than 50%
Part 2 N = 52
inhibition
To compare intermittent vs
continuous schedule
Both 9mg and 13.5mg exceeded the
target coverage
13.5mg selected to provide additional
target coverage
Less TEAEs with intermittent dosing
Narrower dose range
TGI tumor growth inhibition
TEAE Treatment Emergent Adverse Events
Subbiah et al. Ann Oncol 2022
Subbiah et al. Ann Oncol 2022
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