Advertisement


Claire Roddie, PhD, MBChB, on B-ALL: Safety and Efficacy Data of Obecabtagene Autoleucel

2023 ASCO Annual Meeting

Advertisement

Claire Roddie, PhD, MBChB, of University College London, discusses results of the FELIX study, which showed that the second-generation chimeric antigen receptor (CAR) T-cell therapy obecabtagene autoleucel is safe for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, even those with a high burden of disease. This agent yielded high rates of complete response and ongoing CAR T-cell persistence in most patients whose disease responded (Abstract 7000).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Claire Roddie: I'm here today to talk about the FELIX study, that's the study of obe-cel in adult acute lymphoblastic leukemia. Essentially, obe-cel is a novel CD-19 CAR with a fast off rate CD-19 binding domain that confers less toxicity and promotes CAR T-cell persistence. We've tested it with the center I work at in London in a phase one study in 20 patients with acute lymphoblastic leukemia, and the results were so promising that it sparked this phase two endeavor, this FELIX study, which is a global study that's been sponsored by Autolus Therapeutics. To describe this study, essentially, it's an autologous CD-19 CAR T product for patients. They're leukapheresed, they then received bridging chemotherapy, fludarabine cyclophosphamide, and then they receive split dose CAR T-cell infusion over day one and day 10. Essentially, that's again to mitigate for immunotoxicity and they also have their initial dose titrated to disease burden on the prelim food depletion bone marrow.These are all safety features built into the study design. Essentially, on this study we infused 94 patients and given the split dosing, actually on this study, 94% of patients received both doses, which was a really good outcome. The patient population we were dealing with was particularly high risk, so there were a lot of patients with high burden disease. There was a significant portion with extramedullary disease, which we recognized to be a particularly high risk population, so we were dealing with a difficult patient cohort here. But despite that and despite the circulating disease and high burden disease, the manufacture process was extremely successful. 94% of our patients who were leukapheresed had a product released for infusion, which was a great outcome. The event release time on this study was 21 days median. Now in terms of outcomes for these patients, despite the heavy disease burden and the poor risk cohort, actually we saw complete responses in 76% of patients. What's more, those responses were deep responses, so MRD negative in 97% of patients, which is obviously excellent for us as physicians and a lot of those responses were durable, so 61% of the responses were ongoing at that median of 9.5 months. Again, they continued under close observation, that group. Now, this is really probably quite key, the toxicity profile. CAR T-cell therapy is sometimes not very well tolerated by patients, particularly older patients and patients with comorbidities. But this product, this obe-cel cell is unique in that regard. Also, because we're very minimal grade three immunotoxicity on this study. Only 3% of patients experienced grade three CRS and only 7% experienced grade three ICANS, so in a sense this is very different to what's been described with other CAR T-cell therapies for adult acute lymphoblastic leukemia. It makes it a much more appealing potential therapy for these older and more challenging patients. When we look in the blood of these patients, and this is another important feature to recognize, is that at last followup, we're seeing the CAR T cells persisting in these patients right the way up until that median follow-up of 9.5 months. This product continues to proliferate within the patient bloodstream in an ongoing way, continuing to survey the body looking for disease and in an ongoing way immunologically rejecting the leukemia in the event of relapse. That's a very encouraging thing for us as well to see that persistence and we hope that that will lead to durable responses in due course. But that's where we've got to so far with the study and we look forward to updating with more followup as the months go by.

Related Videos

Gynecologic Cancers
Immunotherapy

Bradley J. Monk, MD, on Cervical Cancer: Findings on Pembrolizumab Plus Chemotherapy

Bradley J. Monk, MD, of the University of Arizona, Phoenix, and Creighton University, discusses phase III findings from the KEYNOTE-826 study of overall survival results in patients with persistent, recurrent, or metastatic cervical cancer. Study participants received first-line treatment of pembrolizumab plus chemotherapy, with or without bevacizumab, which reduced the risk of death by up to 40% in three different subsets of patients (Abstract 5500).

Lymphoma

Muhit Özcan, MD, on DLBCL: Now Recruiting Previously Untreated Patients for a Study of Zilovertamab Vedotin Plus Chemotherapy

Muhit Özcan, MD, of Turkey’s Ankara University School of Medicine, discusses waveLINE-007, a two-part study now recruiting in more than 20 locations, to determine the safety and recommended phase II dose of the antibody-drug conjugate zilovertamab vedotin in combination with R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone) in previously untreated patients with diffuse large B-cell lymphoma (DLBCL). Efficacy of this regimen will be investigated in the second half of the study (Abstract TPS7589).

Colorectal Cancer

Cathy Eng, MD, and Lars Henrik Jensen, MD, PhD, on Locally Advanced Colon Cancer: Efficacy of Neoadjuvant Chemotherapy and Standard Treatment

Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center, and Lars Henrik Jensen, MD, PhD, of the Danish Colorectal Cancer Center South and the University Hospital of Southern Denmark, discuss phase III results from the Scandinavian NeoCol trial, which showed that neoadjuvant chemotherapy is not superior to standard upfront surgery in terms of disease-free and overall survival in patients with colon cancer, although there are certain circumstances when this approach may have more favorable outcomes (Abstract LBA3503).

Skin Cancer
Immunotherapy

Allison Betof Warner, MD, PhD, and Adnan Khattak, PhD, MBBS, on High-Risk Resected Melanoma: Survival Results With mRNA-4157 and Pembrolizumab in KEYNOTE-942

Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Adnan Khattak, MBBS, FRACP, PhD, of Australia’s Hollywood Private Hospital & Edith Cowan University, discuss the use of the mRNA-4157 vaccine in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma, which prolonged distant metastasis–free survival compared with pembrolizumab alone. These results provide further evidence that a personalized neoantigen approach is potentially beneficial (Abstract LBA9503).

Lung Cancer

Nagla Abdel Karim, MD, on Small Cell Lung Cancer: SWOG S1929 Results on Atezolizumab Plus Talazoparib

Nagla Abdel Karim, MD, of the Inova Schar Cancer Institute, University of Virginia, discusses phase II data showing that maintenance atezolizumab plus talazoparib improved progression-free survival in Schlafen-11–selected patients with extensive-stage small cell lung cancer. This study demonstrated the feasibility of conducting biomarker-selected trials in this disease, paving the way for future evaluation of novel therapies in selected populations (Abstract 8504).

Advertisement

Advertisement




Advertisement