Camidanlumab Tesirine Elicits Encouraging ORR in Heavily Pretreated Hodgkin Lymphoma

Jay Feingold, MD, PhD

Camidanlumab tesirine (ADCT-301) was found to elicit an objective response rate (ORR) of 66.3% in patients with relapsed/refractory Hodgkin lymphoma, according to interim data from a phase 2 study (NCT04052997) presented during the 16th International Conference on Malignant Lymphoma.¹

Results showed that 67 of 101 patients responded to the antibody-drug conjugate (ADC), with 27.7% achieving a complete response (CR) and 38.6% experiencing a partial response. The median duration of response (DOR) has not yet been reached.

Data from the trial are anticipated to support the submission of a biologics license application seeking the approval of camidanlumab tesirine for use in this population, according to ADC Therapeutics SA, the drug developer.

“The interim results from our ongoing pivotal phase 2 trial of camidanlumab tesirine as a single agent for patients with relapsed or refractory Hodgkin lymphoma demonstrate that a significant number of patients experience long-lasting treatment effects,” Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics, stated in a press release. “In phase 2, we used the optimal phase 1 dosing schedule based on activity and tolerability, and we are encouraged by the interim data that show the median DOR has not been reached.”

The multicenter, open-label, single-arm, phase 2 trial enrolled a total of 117 patients with relapsed or refractory Hodgkin lymphoma who had previously received 3 or more lines of therapy, 2 or more lines if not candidates for hematopoietic stem cell transplantation (HSCT), including previous treatment with brentuximab vedotin (Adcetris) and a checkpoint inhibitor.

To be eligible for enrollment, patients needed to have measurable disease per 2014 Lugano Classification, an ECOG performance status of 0 to 2, and acceptable organ function.² They could not have previously received camidanlumab tesirine, participated on another investigational interventional study, have a known history of hypersensitivity to or positive serum human antidrug antibody to a CD25 antibody, and they could not have undergone allogeneic or autologous transplant within 60 days before treatment initiation.

The primary end point of the trial is ORR, while key secondary end points include DOR, CR, relapse-free survival, progression-free survival, overall survival, fraction of participants who receive HSCT, and safety, among others.

Data from the interim analysis looked at a total of 101 evaluable patients who had been on the study for a median of 5.1 months. Notably, participants were heavily pretreated, having received a median of 6 prior lines of therapy.

Regarding safety, no new signals were reported with the ADC. The most frequent treatment-emergent adverse effects (AEs) that were grade 3 or higher in severity and occurred in 5% or more of patients included hypophosphatemia (7.7%), maculopapular rash (6.8%), thrombocytopenia (6.8%), anemia (6.0%), and lymphopenia (6.0%).

Moreover, 7% of patients (n = 9) were able to undergo HSCT after having received camidanlumab tesirine. Six percent of patients (n = 7/117) developed Guillain-Barré syndrome (GBS)/polyradiculopathy. Incidence of GBS in phase 2 was noted to be consistent with what had been observed in the phase 1 trial of the agent.

“Patients with relapsed or refractory Hodgkin lymphoma who have failed several lines of previous therapy such as brentuximab vedotin and PD-1 blockade have limited treatment options,” Pier Luigi Zinzani, MD, PhD, IRRC Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia “Seràgnoli,” and Departimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, added in the release. “The antitumor activity and safety profile of camidanlumab tesirine continues to demonstrate that this novel CD25-targeted ADC has the potential to address the unmet need in heavily pretreated patients.”

References

1. ADC Therapeutics announces encouraging interim results from pivotal phase 2 clinical trial of camidanlumab tesirine (cam) presented at the 16th Annual International Conference on Malignant Lymphoma. News release. ADC Therapeutics SA. June 22, 2021. Accessed June 22, 2021. https://bit.ly/2Uxbe5f
2. Study to evaluate the efficacy and safety of camidanlumab tesirine (ADCT-301) in patients with relapsed or refractory Hodgkin lymphoma. ClinicalTrials.gov. Updated February 5, 2021. Accessed June 22, 2021. https://clinicaltrials.gov/ct2/show/NCT04052997