Camidanlumab tesirine, an antibody-drug conjugate comprising a human IgG1 anti-CD25 monoclonal antibody conjugated to a pyrrolobenzodiazepine ( PBD ) dimer, displayed antitumor activity and manageable toxicity in a phase 1 trial in lymphoma, including relapsed or refractory classical Hodgkin lymphoma ( R/R cHL ) ( Hamadani et al. 2021 ).
Updated efficacy and safety data from a phase 2 study of Camidanlumab Tesirine monotherapy in patients with R/R classical Hodgkin lymphoma were presented.
Patients with R/R classical Hodgkin lymphoma and 3 or more prior systemic therapies, including Brentuximab vedotin and anti-PD-1 ( 2 or more therapies if hematopoietic cell transplantation [ HCT ] ineligible ), were enrolled.
The primary endpoint is overall response rate ( ORR by 2014 Lugano criteria; central review ). Secondary endpoints include duration of response ( DOR ), progression-free survival ( PFS ), and frequency and severity of adverse events.
Patients received Camidanlumab Tesirine 45 µg/kg ( 30-min infusion ) on day 1 of each 3-week cycle ( 2 cycles ), then 30 µg/kg ( subsequent cycles ) for up to 1 year.
As of Nov 1, 2021, enrollment was complete ( n=117 ). Median age ( range ) was 37 years ( 19-87 ), 62% of patients were male, and 95% had an ECOG score of 0-1.
Patients had received a median ( range ) of 6 ( 3-19 ) prior therapies and received a median ( range ) of 5.0 ( 1-15 ) Camidanlumab Tesirine cycles.
Fourteen patients ( 12.0% ) withdrew to undergo hematopoietic cell transplantation ( of which 12 [ 10.3% ] received hematopoietic cell transplantation and were censored ).
In the all-treated population ( n=117 ), overall response rate was 70.1% ( 82/117; 95% CI: 60.9-78.2 ), and 33.3% ( 39/117 ) had complete response ( CR ).
At median ( range ) follow-up of 10.7 ( 1.2-25.2+ ) months, the median ( 95% CI ) duration of response was 13.7 months ( 7.4-14.7 ) for all responders, 14.5 ( 7.4-not reached, NR ) months and 7.9 ( 3.8-NR ) months for patients with CR or PR, respectively.
Median ( 95% CI ) progression-free survival was 9.1 ( 5.1-15.0 ) months.
All-grade treatment-emergent adverse effects ( TEAEs ) in 25% or more of 117 patients were fatigue ( 45, 38.5% ), maculopapular rash ( MR, 38, 32.5% ), pyrexia ( 35, 29.9% ), nausea ( 32, 27.4% ), and rash ( 31, 26.5% ).
Grade 3 or more TEAEs in 5% or more of patients were thrombocytopenia ( 11, 9.4% ), anemia ( 10, 8.5% ), hypophosphatemia ( 9, 7.7% ), neutropenia ( 9, 7.7% ), maculopapular rash ( 8, 6.8% ), and lymphopenia ( 6, 5.1% ).
TEAEs leading to Camidanlumab Tesirine dose delay / reduction or discontinuation occurred in 66 ( 56.4% ) and 32 ( 27.4% ) patients, respectively.
TEAEs considered PBD-associated were skin / nail reactions ( any grade, 87, 74.4%; grade 3 or more, 24, 20.5% ), hepatobiliary test abnormalities ( any grade, 34, 29.1%; grade 3 or more, 8, 6.8% ), and edema / effusion ( any grade, 20, 17.1%; grade 3 or more, 0 ).
TEAEs considered immune-related occurred in 38 ( 32.5% ) patients. Grade 3 or more immune-related adverse effects ( TEAEs and non-TEAEs; 10, 8.5% ) included diabetic ketoacidosis / type 1 diabetes ( 2, 1.7% ); drug-induced liver injury ( 2, 1.7% ); tubulointerstitial nephritis ( 2, 1.7% ); and aplastic anemia, autoimmune hemolytic anemia or hepatitis, and lichenoid keratosis ( 1 each, 0.9% ).
Guillain–Barré syndrome ( GBS ) / polyradiculopathy was seen in 8 ( 6.8% ) patients ( grade 2, n=2; grade 3, n=3; grade 4, n=3 ).
In 4 patients, onset was after 2 Camidanlumab Tesirine cycles ( range: 2-7 ) and median ( range ) duration was 115 days ( 43-523 ).
At data cutoff, 4 cases had recovered, and 4 had not recovered.
In conclusion, with median follow-up of 10.7 months, Camidanlumab Tesirine has demonstrated an overall response rate of 70.1% ( CR: 33.3% ) in heavily pretreated R/R classical Hodgkin lymphoma after Brentuximab vedotin and PD-1 blockade failure, with an encouraging median duration of response of 13.7 months and median progression-free survival of 9.1 months.
Safety is consistent with prior findings, including similar incidence rates of GBS / polyradiculopathy. ( Xagena )
Carlo-Stella C et al, EHA ( European Hematology Association ) Meeting, 2022