Camidanlumab tesirine is a potential treatment option for relapsed or refractory lymphoma with a tolerable safety profile, particularly in patients with classical Hodgkin lymphoma.
Camidanlumab tesirine is a potential treatment option for relapsed or refractory lymphoma with a tolerable safety profile, particularly in patients with classical Hodgkin lymphoma (cHL), according to findings from a first-in-human study published in The Lancet.
Preclinical models have shown that camidanlumab tesirine has targeted antitumor activity against CD-25 expressing hematological malignancies. Additionally, the agent has exhibited the bystander killing of CD25-negative cells. Potentially, anti-CD25 therapies might modify the tumor microenvironment and induce anti-tumor immunity.
The first in-human trial (NCT02432235) of the agent in patients with relapsed/refractory classical Hodgkin lymphoma (cNHL) included 133 participants. The phase 1, randomized, sequential assignment study had 2 parts, a dose escalation part and a dose expansion part. During the dose escalation portion, doses started at 3 μg/kg every 3 weeks, with a minimum of 2 patients required per cohort. When no dose-limiting toxicities (DLTs) were reported, up to 10 additional participants could be enrolled for the exploration of that dose. More patients could be enrolled if 30% of the 10 patients had a documented partial response or better.
In total, between October 5, 2015 and June 30, 2019, 133 participants were enrolled. Of these patients, 58% had classical Hodgkin lymphoma. Doses administered ranged from 3 μg/kg to 150 μg/kg. Of the 133 participants, 31 were placed in the dose escalation portion, 56 were placed in dose exploration, and 46 in dose expansion. In total, 77 patients with classical Hodgkin lymphoma and 56 patients with NHL were assessed for primary outcomes of patients who experienced DLTs, the recommended phase 2 dose, the number of participants reporting at least 1 treatment-emergent adverse event (TEAE), and the number of participants reporting at least 1 serious TEAE.
Secondary end points included overall response rate, duration of response, progression-free survival, overall survival, maximum observed serum concentration, among others. All patients assessed had relapsed or refractory lymphoma, measurable disease, an ECOG performance status of 0 to 2, and appropriate platelet count and hemoglobin levels at baseline.
In total, between October 5, 2015 and June 30, 2019, 133 participants were enrolled. Of these patients, 58% had classical Hodgkin lymphoma. Doses administered ranged from 3 μg/kg to 150 μg/kg. Of the 133 participants, 31 were placed in the dose escalation portion, 56 were placed in dose exploration, and 46 in dose expansion. In total, 77 patients with classical Hodgkin lymphoma and 56 patients with NHL were assessed for primary outcome.
The maximum-tolerated dose (MTD) was not reached. Of the 86 patients in the dose escalation and exploration assessments evaluated 6% reported dose-limiting toxicities in total. These occurred in a single patient with CHL who received 20 μg/kg of the agent. The patient developed e grade 3 small bowel enteritis and grade 3 oral mucositis. Additionally, 2 patients with CHL who received 30 μg/kg camidanlumab tesirine had grade 3 DLTs, which included one case of increased creatine phosphokinase and one case of skin-related toxicity (pruritus and maculopapular rash). One patient with NHL who received 45 μg/kg camidanlumab tesirine had grade 3 herpes infection. One patient with NHL who received 80 μg/kg of the agent had grade 4 decreased platelet count. Despite the absence of a defined MTD, dose escalation stopped at 150 μg/kg due to the potential of increase toxicity without increased antitumor benefit.
Ninety-nine percent of patients reported an AE of any grade. The most common any grade AEs include fatigue, pyrexia, diarrhea, cough, peripheral oedema, maculopapular rash, decreased appetite, rash, constipation, and dyspnea. Of all AEs, 23% were grade 1-2, 46% were grade 3, 20% were grade 4, and 11% were grade 5. The most common grade 1-2 AEs was fatigue (37%), pyrexia (31%), and diarrhea (26%). The most common grade 3 AEs were maculopapular rash (12%), Increased γ-glutamyltransferase (12%), and anemia (11%). The most common grade 4 AEs was neutropenia (4%), decreased platelet count (4%), and Increased γ-glutamyltransferase (3%). The most common grade 5 AEs reported were acute kidney injury (1%), hypercalcemia (1%), and lung infection (1%).
TEAEs leading to dose delays occurred in 44% of patients and 23% of patients had 1 or more TEAEs that lead to therapy discontinuation. Five percent of patients had infusion reactions. Additionally, a small number of autoimmune toxicities were also reported, with peripheral sensory neuropathy in 7% of patients and hypothyroidism in 6% of patients. Additionally, 4% of patients developed Guillain-Barré syndrome. All events occurred in patients with CHL, 60% of which had received previous checkpoint inhibitor therapy and 100% received brentuximab vedotin. In over half of the incidences, they syndrome resolved with medical management.
The objective response rate (ORR) for the total population was 58%, with 29% achieving a complete response (CR). The ORR for patients with cHL was 71%, with 42% of this patient population reporting a CR. In patients with NHL, the ORR was 38% with 9% of patients reporting a CR. In patients with cHL who received 45 μg/kg camidanlumab tesirine, the ORR was 86% with 49% reporting a complete response rate. Additionally, for patients at this dose level who previously received brentuximab vedotin, the ORR was 86% and 88% for those who received brentuximab vedotin and a checkpoint inhibitor.
The median DOR for patients cHL was 6.6 months and 7.2 months for patients who received 45 μg/kg camidanlumab tesirine. For patients with a CR, the median DOR was 8.1 months. The median PFS was 6.8 months for all doses and 7.0 months for those at the 45 μg/kg camidanlumab tesirine level. Fifty-six percent of patients, with cHL received subsequent anticancer therapy.