Swaminathan P. Iyer, MD, of the University of Texas MD Anderson Cancer Center, explains the mechanism of action and efficacy/safety observed in phase 1 results of CTX130, a CD70-targeted allogeneic chimeric antigen receptor (CAR) T-cell therapy, in the treatment of relapsed/refractory T-cell lymphoma.
An acceptable safety profile and durable complete response (CR), partial response (PR) rates were observed with the chimeric antigen receptor (CAR) T-cell therapy CTX130 in the phase 1 COBALT-LYM study of patients with relapsed/refractory T-cell lymphomas, said Swaminathan P. Iyer, MD, professor of medicine in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center.
Iyer served as lead author of a study presented today at the 2022 European Hematology Association (EHA) Congress, titled, "The COBALT-LYM Study of CTX130: A Phase 1 Dose Escalation Study of CD70-Targeted Allogeneic CRISPR-Cas9–Engineered CAR-T Cells in Patients with Relapsed/Refractory (R/R) T-cell Malignancies.”
What is the mechanism of action for CTX130 in T-cell lymphoma, and can you discuss how the COBALT-LYM study was conducted?
So, CTX130 is a first-in-class allogeneic CAR T-cell for T-cell lymphomas. And the study that put together this CAR T was called the COBALT-LYM study, and the target here is CD70, [which] is a protein that is expressed on the surface of cells. It's been found that 85% of T-cell lymphomas express them.
A lot of investigations of the past have been done on CD70 in terms of antibodies and antibody drug conjugates. What's different about this construct, it's an allogeneic CAR T, which means healthy donors are selected and the chimeric antigen receptor is created using CD70 as a construct, and using the other activation and costimulatory domains.
This is the product, CTX130, and this a phase 1 dose-finding study allowable in patients who express at least greater than 10% of CD70 in patients with PTCL [peripheral t-cell lymphoma] and patients with CTCL [transformed cutaneous t-cell lymphoma]. For PTCL, the prior criteria is one prior line of therapy, for CTCL it’s at least 2 systemic therapies.
The patients were enrolled, and you will see the presentation this afternoon, from the abstract, it's 18 patients’ data who participated in this study, and 70% overall response rate and 29% CR based on the abstract. So, this is the CTX130, and there's more data that will be presented this afternoon.
Can you discuss efficacy and safety findings reported at EHA2022 of the COBALT-LYM study?
So, the first thing is safety. Since it's a dose-finding study, phase 1, the main goal of part A, which is the dose escalation, is safety. Since it's a CAR T construct, it has certain potential side effects that are very different from other drugs, if you will.
So, the things that you would expect in CAR Ts are cytokine release syndrome [CRS], the neurological toxicity called ICANS [immune effector cell-associated neurotoxicity syndrome], and since it’s an allogeneic CAR T, GVHD [graft versus host disease], and since it's an effective therapy, tumor lysis syndrome (TLS), and then everything else that other drugs might cause.
So, in this particular study, the safety was acceptable across all those levels—4 of those levels tested, 1, 2, 3, and 4, going from 30 to 900 million cells, and the safety was acceptable. The CRS was mostly grade 1 and 2, the neurological toxicity was grade 1 and 2, all of which resolved. There was no TLS, no GVHD.
There were some infections seen. One out of the 4 infections of the grade 3 or higher were attributable to the CAR T, but otherwise, there are other treatment-emergent SAEs [serious adverse events], such as syncope, presyncope, tumor hemorrhage—they were all not deemed related to CTX130. So, safety wise, very acceptable.
Efficacy, I just mentioned 70% overall response rate with 29% CRs. And some of these CRs were durable CRs. You will see that many of them could be bridged to the more longer-term consolidation therapy. But for the first time you're seeing responses in T-cell lymphomas, patients who did not achieve prior responses like a CR, and now we're getting to the point where you have PRs and CRs that are lasting.