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Nivolumab exposure and tumor-size dynamics

An exposure-response model connecting nivolumab steady-state exposure to competing tumor shrinkage and progression processes and their resulting tumor-size trajectory.

Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy ↗

Journal for ImmunoTherapy of Cancer

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MODEL IN MOTION 18 sec

How do the three joint-fit tumor contexts evolve over time?

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joint MEL 3 mg/kg, Cminss 85 ug/mL

How does nivolumab exposure shift the balance between tumor shrinkage and progression? Explore this biological starting configuration through Steady-state trough concentration, Tumor size, Tumor size relative to baseline.

0–52 week

Scenario details

joint MEL 3 mg/kg, Cminss 85 ug/mL

How does nivolumab exposure shift the balance between tumor shrinkage and progression? Explore this biological starting configuration through Steady-state trough concentration, Tumor size, Tumor size relative to baseline.

Readouts

Steady-state trough concentration · Unit unavailable
Steady-state trough concentration over the selected simulation window.
Tumor size · mm
Tumor size over the selected simulation window.
Tumor size relative to baseline · percent
Tumor size relative to baseline over the selected simulation window.

Study purpose

  • How does nivolumab exposure shift the balance between tumor shrinkage and progression?

Inputs changed since the displayed result. Run to update the comparison.

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Model parameter

Steady-state trough concentration coefficient used by the released system of model equations.

µg/mL

Suggested: 42.5–128. You can explore beyond this range.

85 → —

Maximum tumor shrinkage rate defining the limiting magnitude of the corresponding pharmacodynamic effect.

1/week

Suggested: 0.00728–0.0218. You can explore beyond this range.

0.01455 → —

Tumor-shrinkage half-maximal concentration at which the corresponding modeled effect reaches half of its maximum.

µg/mL

Suggested: 28.4–85.3. You can explore beyond this range.

56.89 → —

Minimum tumor progression rate defining the limiting magnitude of the corresponding pharmacodynamic effect.

mm/week

Suggested: 0.0888–0.266. You can explore beyond this range.

0.1776 → —

Tumor-progression half-maximal concentration at which the corresponding modeled effect reaches half of its maximum.

µg/mL

Suggested: 5.16–15.5. You can explore beyond this range.

10.33 → —
Simulation time
week
week
52 → 168

Time between reported samples.

week
0.25 → 1

2 changes · Variation 1

Continue in the background and keep the result.

Biology

A scenario-defined steady-state nivolumab trough concentration independently changes an empirical tumor-shrinkage rate and tumor-progression rate. Those opposing drives determine the exploratory tumor-size trajectory.

How does fixed nivolumab trough exposure shift tumor shrinkage and progression?A scenario-defined steady-state nivolumab trough concentration independently changes an empirical tumor-shrinkage rate and tumor-progression rate. Those opposing drives determine the exploratory tumor-size trajectory.BIOLOGY OVERVIEWHow does fixed nivolumab trough exposure shift tumor shrinkage and progression?Fixed trough exposure: Scenario-defined nivolumab CminssFixed troughexposureScenario-defined nivolumabCminssShrinkage drive: Exposure-dependent empirical rateShrinkage driveExposure-dependent empiricalrateProgression drive: Exposure-dependent empirical rateProgression driveExposure-dependent empiricalrateTumor size: Net shrinkage and progressionTumor sizeNet shrinkage and progressionPRIMARY READOUTSSteady-state trough exposureSteady-state trough exposu…Exploratory tumor sizeExploratory tumor sizeTumor size relative to baselineTumor size relative to bas…

Solid arrows show modeled movement or change; two-headed arrows show reversible exchange; dashed arrows show modulation without material transfer.

Model scope: Nivolumab dosing or PK, clearance, PD-1 binding or occupancy, immune-cell activation, population variability, and causal dose recommendations are not represented.

Modeled relationships (4)
  • Fixed trough exposure → Shrinkage drive: sets shrinkage (modulation)
  • Fixed trough exposure → Progression drive: sets progression (modulation)
  • Shrinkage drive → Tumor size: tumor reduction (loss)
  • Progression drive → Tumor size: tumor increase (production)

Modeled relationships: Fixed trough exposure to Shrinkage drive: sets shrinkage (modulation); Fixed trough exposure to Progression drive: sets progression (modulation); Shrinkage drive to Tumor size: tumor reduction (loss); Progression drive to Tumor size: tumor increase (production).

Primary readouts: Steady-state trough exposure; Exploratory tumor size; Tumor size relative to baseline.

Model details

12 parameters · 4 states · 4 equations · 6 derived outputs

Classification & API access
Therapeutic
Nivolumab
Modality
Monoclonal antibody
Target
PD-1 / PDCD1
Disease / scope
Melanoma, non-small cell lung cancer, and renal cell carcinoma
ParameterDefaultUnitDescription
Baseline tumor size percentbaseline_tumor_size_percent100percentBaseline tumor size percent coefficient used by the released system of model equations.
Baseline tumor size mmexploratory_baseline_tumor_size_mm80mmBaseline tumor size mm coefficient used by the released system of model equations.
Steady-state trough concentrationexploratory_cminss_ug_mL65µg/mLSteady-state trough concentration coefficient used by the released system of model equations.
Tumor-growth dynamics PR0exploratory_tgd_pr01.8mm/weekTumor-growth dynamics PR0 coefficient used by the released system of model equations.
Tumor-progression half-maximal concentrationexploratory_tgd_pr_ec5012.04238519µg/mLTumor-progression half-maximal concentration at which the corresponding modeled effect reaches half of its maximum.
Tumor-growth dynamics pr hillexploratory_tgd_pr_hill1.078878937—Tumor-growth dynamics pr hill coefficient used by the released system of model equations.
Minimum tumor progression rateexploratory_tgd_prmin0.4594683975mm/weekMinimum tumor progression rate defining the limiting magnitude of the corresponding pharmacodynamic effect.
Tumor-growth dynamics SR0exploratory_tgd_sr00.0111/weekTumor-growth dynamics SR0 coefficient used by the released system of model equations.
Tumor-shrinkage half-maximal concentrationexploratory_tgd_sr_ec5093.46711474µg/mLTumor-shrinkage half-maximal concentration at which the corresponding modeled effect reaches half of its maximum.
Maximum tumor shrinkage rateexploratory_tgd_srmax0.01339778411/weekMaximum tumor shrinkage rate defining the limiting magnitude of the corresponding pharmacodynamic effect.
Progression rate percentprogression_rate_percent_per_week0percent/weekProgression rate percent coefficient used by the released system of model equations.
Shrinkage rateshrinkage_rate_per_week01/weekShrinkage rate coefficient used by the released system of model equations.

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