Exploratory Analysis of Factors Influencing Efficacy and Safety of Camidanlumab Tesirine: Data from the Open-Label, Multicenter, Phase 2 Study of Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL)

Abstract

Introduction: Despite most patients with cHL being cured with standard therapies, a proportion of patients are refractory or relapse after first- and second-line treatments (1L/2L), including stem cell transplantation, and there are limited treatment options available after failure of brentuximab vedotin (BV) and PD-1 blockade. Camidanlumab tesirine (Cami) is an antibody-drug conjugate comprising an anti-CD25 monoclonal antibody conjugated through a cleavable linker to a pyrrolobenzodiazepine (PBD) dimer. Cami has shown notable single-agent anti-tumor activity and manageable toxicity in the Phase 2 trial of patients with R/R cHL (Carlo-Stella et al, Hemasphere 2022;6:102-103). Objectives: To assess the clinical response and safety of Cami by subgroups based on demographics, known risk factors impacting outcomes in patients with R/R cHL, and factors with potential relevance to Cami's mechanism of action. Methods: This analysis was based on the open-label, multicenter, Phase 2 study of Cami monotherapy in patients with R/R cHL after ≥3 prior lines of therapy (NCT04052997). Cami was administered (30-minute infusion) on day 1 of each 3-week cycle at 45 µg/kg for 2 cycles, then 30 µg/kg for subsequent cycles. Subgroup analyses (data cutoff: March 16, 2022) were conducted (Table 1). Efficacy outcomes included the overall response rate (ORR) and median duration of response (mDOR); statistical significance was assessed by comparison of 95% confidence intervals. Safety was assessed by incidence of treatment emergent adverse events (TEAEs). Results: There were no significant differences in efficacy outcomes between demographic subgroups based on age or sex (Table 1). The ORR was similar for patients who were refractory or relapsed after 1L therapy (72.4% vs 72.2%). Despite the higher number of patients who were refractory after last line therapy versus those who relapsed, the ORR was not significantly different between the two groups (68.2% vs 78.4%). The response to Cami did not depend on the prior response to PD-1 inhibition or the time since the last PD-1 inhibitor use. The ORR was similar for patients who were refractory to PD-1 inhibition or relapsed (66.2% vs 75.8%) and for patients who were treated with Cami ≤4 months and >4 months since the last PD-1 inhibitor (69.0% vs 71.7%). No statistically significant differences in the ORR were observed based on the number of prior lines of therapy, prior HSCT, or region. However, the complete response rate (CRR) for patients who received prior HSCT was 41.9% vs 18.6% in patients without HSCT; the mDOR was 13.73 months in patients with prior HSCT vs 5.85 in patients without prior HSCT. Median DOR was similar between North American (NA) and European (EU) patients (13.77 months vs 13.73 months). However, NA patients had improved CRR vs EU patients (44.6% vs 23%), and differences were more pronounced in NA vs EU patients with prior HSCT (52.4% vs 28.1%). Cami's tolerability was similar across most subgroups. The safety profile of Cami was similar in older compared with younger patients, as indicated by similar incidences of TEAEs overall, grade ≥3 TEAEs, and groupings by system organ class. The incidence of any grade TEAEs was similar between NA and EU patients (100% vs 98.4%). Patients with prior HSCT had more grade ≥3 TEAEs vs those without prior HSCT (73% vs 58.1%). Conclusions: Evidence from preliminary subgroup analyses suggests that response to Cami was independent of age, sex, and response to and timing of last PD-1 inhibitor. Differences in Cami's safety and efficacy were noted by prior transplant and region. Although a difference in CRR was observed between NA and EU, this did not result in a difference in mDOR or ORR between the two regions. These preliminary analyses should be interpreted with caution as subgroups were small and limited in statistical comparison. Exploratory analyses to identify predictive markers of GBS/polyradiculopathy observed in Cami trials are ongoing and results will be also presented. These results suggest that Cami shows antitumor activity across patient subgroups, including heavily pretreated and older patients. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal