S201: Camidanlumab Tesirine: Updated Efficacy and Safety in an Open-label, Multicenter, Phase 2 Study of Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (r/r Chl)
Year: 2022
Type: article
Abstract: Background: Camidanlumab tesirine (Cami), 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 R/R cHL (Hamadani et al. 2021). Aims: Present updated efficacy and safety data from a phase 2 study of Cami monotherapy in patients (pts) with R/R cHL (NCT04052997). Methods: Pts with R/R cHL and ≥3 prior systemic therapies, including brentuximab vedotin (BV) and anti-PD-1 (≥2 therapies if hematopoietic cell transplantation [HCT] ineligible), were enrolled. Interim data was reported (Herrera et al. 2020, Zinzani et al. 2021). 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 (AEs). Pts received Cami 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. Results: As of Nov 1, 2021, enrollment was complete (N=117). Median age (range) was 37 years (19-87), 62% of pts were male, and 95% had an ECOG score of 0-1. Pts had received a median (range) of 6 (3-19) prior therapies and received a median (range) of 5.0 (1-15) Cami cycles. Fourteen pts (12.0%) withdrew to undergo HCT (of which 12 [10.3%] received HCT and were censored). In the all-treated population (N=117), ORR was 70.1% (82/117; 95% CI: 60.9-78.2), and 33.3% (39/117) had complete response (CR) (Fig 1A). At median (range) follow-up of 10.7 (1.2-25.2+) months (mos), the median (95% CI) DOR was 13.7 mos (7.4-14.7) for all responders, 14.5 (7.4-not reached, NR) mos and 7.9 (3.8-NR) mos for pts with CR or PR, respectively (Fig 1B). Median (95% CI) PFS was 9.1 (5.1-15.0) mos. All-grade treatment-emergent AEs (TEAEs) in ≥25% of 117 pts 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 TEAEs in ≥5% of pts were thrombocytopenia (11, 9.4%), anemia (10, 8.5%), hypophosphatemia (9, 7.7%), neutropenia (9, 7.7%), MR (8, 6.8%), and lymphopenia (6, 5.1%). TEAEs leading to Cami dose delay/reduction or discontinuation occurred in 66 (56.4%) and 32 (27.4%) pts, respectively. TEAEs considered PBD-associated were skin/nail reactions (any grade, 87, 74.4%; grade ≥3, 24, 20.5%), hepatobiliary test abnormalities (any grade, 34, 29.1%; grade ≥3, 8, 6.8%), and edema/effusion (any grade, 20, 17.1%; grade ≥3, 0). TEAEs considered immune-related (IR) occurred in 38 (32.5%) pts. Grade ≥3 IR AEs (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%) pts (Grade 2, n=2; grade 3, n=3; grade 4, n=3). In 4 pts, onset was after 2 Cami 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. Image:Summary/Conclusion: With median follow-up of 10.7 mos, Cami demonstrated an ORR of 70.1% (CR: 33.3%) in heavily pretreated R/R cHL after BV and PD-1 blockade failure, with an encouraging median DOR of 13.7 mos and median PFS of 9.1 mos. Safety is consistent with prior findings, including similar incidence rates of GBS/polyradiculopathy.
Source: HemaSphere
Authors: C. Carlo-Stella, S. Ansell, P. L Zinzani, J. Radford, K. Maddocks, A. Pinto, G. P. Collins, V. Bachanova, N. Bartlett, I. Bence-Bruckler, M. Hamadani, J. Kline, J. Mayer, K. J. Savage, R. Advani, P. Caimi, R.-O. Casasnovas, T. Feldman, B. Hess, M. Bastos-Oreiro, S. Iyengar, S. Eisen, Y. Negievich, L. Wang, J. Wuerthner, A. F. Herrera
Institutions: Humanitas University, IRCCS Humanitas Research Hospital, Mayo Clinic, University of Bologna, Manchester Academic Health Science Centre, University of Manchester, The Christie NHS Foundation Trust, NIHR Manchester Clinical Research Facility, The Ohio State University Wexner Medical Center, The Ohio State University, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Churchill Hospital, NIHR Oxford Biomedical Research Centre, University of Minnesota, Washington University in St. Louis, Ottawa Hospital, Medical College of Wisconsin, University of Chicago, Masaryk University, University Hospital Brno, University of British Columbia, Stanford Medicine, Stanford University, Cleveland Clinic, Case Comprehensive Cancer Center, Inserm, Hackensack Meridian Health, Medical University of South Carolina, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Royal Marsden Hospital, Adc Therapeutics (Switzerland), City Of Hope National Medical Center, City of Hope
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W4283312807