SOCRA 2024 Annual Conference Program Book - Flipbook - Page 56
Delayed immune‐related toxicities
Low‐grade
chronic
toxicities may
negatively
impact dosing
with targeted
therapy
Infigratinib 125mg 3 weeks on and 1 week off
Not able to keep dose intensity beyond 48 days
Javle et al. JCO 2017
Martins et al. Nat Rev Clin Oncol 2019
From ICH 1994 to Optimus…
The promise of precision medicine
The right drug, to the right patient at the right time…and
at the right dose!!
“Sponsors should carefully evaluate exposure‐
response, efficacy and safety data from early trials
to inform dose selection”
ICH E4 Guideline 10 March 1994
Benefits of improved dose selection at early stages
Decreased toxicities
Drug development hampered by lack of robust dose exploration
Doses/schedules of oncology drugs are often not well characterized
Short DLT windows to evaluate MTD:
Decreased costs (reduce AEs)
SAE may occur after multiple cycles
MTA increasing doses beyond certain level may not increase activity
Improved GO/No‐GO decisions
If drug to be used months/years then long‐term tolerability is key
Dose selection should be guided by efficacy, PK, PD data
Faster drug approvals
More convenient dosing schedules: q6w vs q3w (pembro during COVID), SC vs IV
Shat et al. NEJM 2021
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