KEY TAKEAWAYS
- The phase 1 of ALNUC trial aimed to report the long-term follow-up of IV ALNUC and evaluate the safety and efficacy of SC ALNUC in patients with RRMM.
- RRMM patients who had received three prior lines of treatment were enrolled in the study. IV ALNUC was administered at varying doses, while SC ALNUC was given in escalating doses and dose expansions.
- IV ALNUC demonstrated clinical activity, with a response rate of 39% and a median DOR of 33.6 months.
- The most common adverse events associated with SC ALNUC were CRS, neutropenia, infections, anemia, and thrombocytopenia.
- IV ALNUC demonstrated sustained responses in heavily treated RRMM patients, while SC ALNUC showed dose-dependent anticancer activity and reduced the severity of CRS.
ALNUC, a 2+1 T-cell engager (TCE) with bivalent BCMA binding, showed clinical activity in RRMM patients in an open-label phase 1 research (NCT03486067). IV-administered ALNUC had a long DOR but caused CRS in 76% of patients. Subcutaneous (SC) dosage lowered CRS rate and severity, permitting greater target doses and promising antitumor activity. To report long-term IV ALNUC follow-up and SC ALNUC safety and efficacy in phase 1 RRMM patients. Patients received three prior lines of treatment (LOTs): immunomodulatory, proteasome inhibitor, and anti-CD38. IV ALNUC was dosed at 0.15–10 mg with fixed and step-up dosing (Costa LJ et al. Blood 2019). SC ALNUC was given on d 1, 4, 8, 15, and 22 of cycle 1 (C1), QW in C2–3, Q2W in C4–6, and Q4W in C7 and beyond (28-d processes). C1D1 (3 mg) and C1D4 (6 mg) received step-up doses, and C1D8 later received target doses (>10 mg). About 70 points got IV ALNUC. Around 39% (27/70) responded, with a median DOR of 33.6 mo (95% CI, 10.6–NA). The median PFS was 3.1 months (1.9–5.5). 53 (76%) patients had CRS, and 5 (7%) had grade(G) 3.
SC ALNUC was administered to 73 patients in dosage escalation (10 mg, 6; 15 mg, 4; 30 mg, 6; 60 mg, 7) and dose expansion (10 mg, 19; 30 mg, 21; 60 mg, 10), with a median age of 64 years and 42% female. About 93% were refractory to final LOT, 100%/63% had triple-class exposed/refractory MM, and 66%/26% had penta-drug-exposed/refractory MM. At the data cutoff, 39 (53%) patients still received treatment after 4.3 months (0.5–16.0). CRS (56%/0%), neutropenia (49%/42%), infections (47%/10%), anemia (41%/25%), and thrombocytopenia (33%/14%) were the most common TEAEs in SC patients. All CRS occurrences were G1 (44%; 32/73) or G2 (12%; 9/73); 35 (48%) pts received ≥1 concomitant medication for CRS, including tocilizumab (30%; 22/73) and corticosteroids (15%; 11/73). Median time to CRS was 3 d (1–20); median duration was 2 d (1–11). Two patients experienced SC ALNUC-related G1 neurotoxicity. One patient terminated therapy owing to a TEAE (G3 metastatic colon cancer not presumed related to treatment), and one died of a cerebral hemorrhage at the 60-mg target dose. SC ALNUC bioavailability with 15-d T1 was ~61%.
Trough concentrations at the 30-mg target dose exceeded C2D1 efficacy predictions. SC and IV ALNUC showed TCE pharmacodynamics. SC ALNUC had 53% ORR across all amounts and 65% at the 30-mg target dose in 55 efficacy-evaluable patients. About 16 of 20 evaluable minimal residual disease (MRD) samples from 29 responders were MRD-negative (80%; 10-5 sensitivity by flow cytometry) at C2D1 or C4D1. Around 25 responses (86%) were ongoing. The median response time was 1.0 months (95% CI, 0.7–1.3). IV ALNUC sustained responses in severely pretreated RRMM patients. SC ALNUC reduced CRS to low-grade, short-lived occurrences. SC ALNUC showed dose-dependent anticancer activity and MRD negative in most responders.
Source: https://library.ehaweb.org/eha/2023/eha2023-congress/386712/sandy.w.wong.alnuctamab.28alnuc.bms-986349.cc-9326929.a.bcma.cd3.t-cell.engager.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03486067
Sandy W. Wong, Noffar Bar, María Victoria Mateos, Paz Ribas, Markus Hansson, Laura Paris, Craig Hofmeister, Paula Rodriguez-Otero, Maria Aranzazu Bermúdez, Armando Santoro, Andrew J. Yee, Maria Creignou, Cristina Encinas, Claudio Cerchione, Javier de la Rubia, Albert Oriol, Barbara Ferstl, Britta Besemer, Jinjie Chen, Alexander Chung, Isaac W. Boss, Allison Gaudy, Shaoyi Li, Kevin Hsu, Colin Godwin, Michael R. Burgess, Jesús San-Miguel, Luciano Jose Costa
/ALNUCTAMAB (ALNUC; BMS-986349; CC-93269), A BCMA × CD3 T-CELL ENGAGER, IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): LATEST RESULTS FROM A PHASE 1 FIRST-IN-HUMAN CLINICAL STUDY/ Inc, M. G. (n.d.). ALNUCTAMAB (ALNUC; BMS-986349; CC-93269), A BCMA × CD3 T-CELL… by Dr. Sandy W. Wong. Library.ehaweb.org. Retrieved July 14, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/386712/sandy.w.wong.alnuctamab.28alnuc.bms-986349.cc-9326929.a.bcma.cd3.t-cell.engager.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27922%2Atrend%3D4016%2Amarker%3D4178
