Galapagos Pauses Enrollment in Multiple Myeloma CAR-T Trial After Parkinsonism Case
The company has filed a protocol amendment with the EMA and anticipates resuming recruitment imminently.
Jeevan Shetty, MD
Credit: Galapagos
Galapagos has paused enrollment in its phase 1/2 PAPILIO-1study evaluating GLPG5301 chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory multiple myeloma (rrMM) after at least 2 prior lines of therapy after a patient developed a case of Parkinsonism.1
Cases of Parkinsonism have occurred after treatment with other CAR T-cell therapies. Notably, Janssen’s black box warning for ciltacabtagene autoleucel (Carvykti) includes a warning for Parkinsonism and Bristol-Myers Squibb’s black box warning for idecabtagene vicleucel (Abecma) mentions a grade 3 Parkinsonism adverse event (AE).2,3
Galapagos said in an earnings call that it paused enrollment out of an abundance of caution to closely look at the case. It has filed a protocol amendment with the European Medicines Agency and anticipates resuming recruitment imminently. Galapagos will also share data from the study in 2025.
GLPG5301 is a BCMA-targeted, 7-day vein-to-vein, point-of-care manufactured CAR-T candidate being evaluated for safety and tolerability in PAPILIO-1. During Phase 1, up to 3 dose levels will be evaluated in at least 12 patients to establish the recommended Phase 2 dose, which will be evaluated in approximately 30 additional patients in the Phase 2 part of the study to confirm GLPG5301’s safety and efficacy. The company dosed the first patient in the PAPILIO-1 study in December 2023.4
READ MORE: New Study Recommends Shorter, Flexible Monitoring After CAR T-Cell Therapy
“Patients living with rrMM have a very poor prognosis and a significant high unmet medical need for novel treatment options. CAR-T therapy is one such option. By combining innovative science with breakthrough point-of-care delivery of novel CAR-T therapies, we aim to enhance patient outcomes and improve their quality of life,” Jeevan Shetty, MD, Head, Clinical Development Oncology, Galapagos, said in a statement at that time.4 “We are very pleased that the first patient with rrMM in PAPILIO-1 has been dosed with our BCMA CAR-T candidate, GLPG5301. This marks another milestone in the roll-out of our point-of-care network and the build-up of our CAR-T portfolio, which now consists of 3 ongoing clinical programs in severe hemato-oncology indications.”
In more positive news, Galapagos announced positive data from its CD19-targeted CAR-T candidate GLPG5101 in patients with non-Hodgkin lymphoma at the annual European Hematology Association (EHA) 2024 Hybrid Congress in June from the Phase 1/2 ATALANTA-1 study.5
The data, updated as of December 20, 2023, were from 333 patients in the safety set and 33 in the efficacy set (34 total have been dosed). Investigators observed a manageable safety profile, with 2 cases of grade 3 cytokine release syndrome (CRS) and 1 case of grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS). Other treatment-emergent AEs were mild.5
Investigators observed an 87.5% overall response rate (ORR), with a 75% complete response (CR) rate in the phase 1 part and a 93.3% ORR and CR rate in the phase 2 part of the study. By indication, patients with diffuse large B-cell lymphoma had a 78% ORR and 56% CR rate, patients with follicular lymphoma or marginal zone lymphoma had a 94% ORR and CR rate, and patients with mantle cell lymphoma had a 100% ORR and CR rate.5
At a median follow-up of 13.1 months in the phase 1 part of the study, 71% of patients had an ongoing response. At a median follow-up of 4.2 months in the phase 2 part, 100% of patients had an ongoing response.5
“We are committed to accelerating breakthrough innovations to extend the reach of CAR-T therapies to patients with rapidly progressing cancers,” Shetty said in a statement.5 “We are delighted to present promising new data for GLPG5101 at the EHA congress. The high CR rates, combined with low-grade CRS and ICANS, demonstrates the potential of GLPG5101 in addressing the critical needs of this patient population. The data also confirm the feasibility of our innovative decentralized T-cell manufacturing platform in delivering fresh, fit cells with a median vein-to-vein time of just 7 days.”
