Cancer Chemother Pharmacol: Analysis of exposure response of camimedan mab tercillin in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma

Lymphomas are a heterogeneous group of lymphatic malignancies that can be broadly classified as either Hodgkin lymphoma or non-Hodgkin lymphoma
.
Camidarumab (Cami; ADCT-301) is an antibody-drug conjugate consisting of the human monoclonal antibody HuMax-TAC (GenMab, Copenhagen, Denmark) targeting human CD25 and conjugated
to SG3199, a pyrrolidine benzodiazepine (PBD) dimeric cytotoxin, via a cleavable linker.
To determine the appropriate dosing regimen for Cami for future trials, it is necessary to thoroughly characterize
the pharmacokinetics (PK) in lymphoma patients.
One study used a comprehensive population-based pharmacokinetic model to study the exposure-response (E-R) relationship
of camimumab tiecillin (Cami) in patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma.

Research exploratory analyses investigated the relationship between exposure measures and the occurrence
of binary and non-binary variables (overall survival [OS]).
Exploratory analysis showed a significant positive correlation
between exposure and ORR/OS.
The final model shows that this effect is not significant
due to the covariate effect.
Patients with selected ≥ grade 2AEs had higher Cami exposure at cycle 6 (expected steady-state exposure levels), as confirmed
in the final E-R model.

Figure 1: Boxplot of model-predicted exposure, stratified
by grade A≥ increased GGT at cycle 6 by grade 2, increased neurological adverse events at cycle 2 at grade B≥, and increased GGT and 2 autoimmune adverse events at cycle 6 at grade C≥ 2 autoimmune adverse events at cycle 6.
Blue dots represent individual patients; The line represents the average concentration value; Whiskers indicate minimum and maximum values
.

Figure 2: VPCs as the final logistic regression model, with A Cmaxss, B baseline soluble CD25, and a quarter of total C-baseline bilirubin as a quarter
of the objective response rate for cHL patients.

Figure 3: The effect
of model prediction of Cami Cmaxss status on the estimated overall survival probability of cHL patients at cycle 6.
Cmaxss is a steady-state maximum serum concentration at cycle 6

Based on univariate results, _Cmax was used as an exposure measure in all models except the autoimmune AE all-E-R model, where C _averages were used
.
In the final model, there was no statistically significant
positive correlation between exposure and ORR/OS (higher exposure is significantly associated with higher ORR/OS probability).
The final safety E-R model showed a significant positive correlation between Cami exposure and selected level 2 ≥AEs, with higher exposures associated with a higher probability of experiencing level 2 AEs ≥ in cycle 6
.

Overall, the study identified preliminary predictors of efficacy and safety, and provided a basis for
Cami dose rationale and benefit-risk profile in patients with relapsed/refractory cHL.

Original source:

Toukam, M.
, Boni, J.
P.
, Hamadani, M.
 et al.
 Exposure–response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma.
 Cancer Chemother Pharmacol (2022).
https://doi.
org/10.
1007/s00280-022-04487-3