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)

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.

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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.