Afrigather NEW ORLEANS — Chimeric antigen receptor T-cell (CAR T) remedy has performed spectacular outcomes in sufferers with hematologic cancers, nonetheless identical results for those with stable tumors possess remained elusive.
Now, a brand recent CAR T assemble that targets the tumor-explicit antigen claudin 6 (CLDN6) is showing promising preliminary job in opposition to relapsed or refractory superior stable tumors, especially testicular and ovarian cancers, early files demonstrate.
This recent CAR T remedy, delivered as monotherapy and along with an mRNA vaccine engineered to lift T-cell responses, confirmed “sturdy engraftment” of T cells 6 weeks after infusion, researchers reported in a allotment 1 trial.
Among 14 evaluable sufferers with CLDN6-definite stable tumors, six skilled a partial response to remedy — four who bought CAR T monotherapy, and two who bought the mix CAR T agent and vaccine, dubbed BNT211.
“CLDN6 was never focused sooner than with cell remedy, nonetheless in our see, this vogue is already showing efficacy which can be better than the knowledge from a range of CAR T trials in stable tumors,” lead investigator Johan Haanen, MD, PhD, from the Netherlands Cancer Institute in Amsterdam, stated in an announcement.
On April 10, Haanen presented early files from this first-in-human originate-tag, multicenter clinical trial at the American Association for Cancer Study (AACR) Annual Assembly 2022.
To this point, use of CAR T remedy to handle stable tumors has been disappointing. It has largely been hampered by difficulties identifying targets that spare wholesome cells while placing forward an adequate T-cell response over time.
Claudin 6 represents a promising target for the reason that protein is aberrantly expressed in a range of cancers, along side testicular, ovarian, uterine, and lung most cancers, even supposing no longer in wholesome grownup tissue.
In the present allotment 1 trial, Haanen and colleagues focused on sufferers with relapsed or refractory superior stable tumors with tumor cells that expressed claudin 6.
In allotment 1 of the 2-allotment see, sufferers bought escalated doses of CLDN6 CAR T monotherapy, following lymphodepletion. In allotment 2, sufferers bought escalated doses of the mix BNT211 remedy, with the mRNA vaccine (CARVac) administered each and each 2 to three weeks for as a lot as 100 days after CAR T-cell transfer.
As of March 10, the see included 16 sufferers — eight with testicular most cancers, four with ovarian most cancers, and 4 with a range of forms of tumor. At the time of files cutoff, 14 sufferers possess been evaluable for secondary efficacy endpoints.
Among these sufferers, four sufferers with testicular most cancers and two with ovarian most cancers skilled a partial response, for an goal response rate of 43%. The tempo of illness management rate was 86%. The investigators also seen deepening of the partial responses 12 weeks after infusion.
The remedy confirmed particular promise in five sufferers with testicular most cancers handled at the simpler of the 2 doses, with one full response, three partial responses, and one case of stable illness. This community performed an goal response rate of 80% and a illness management rate of 100%.
In the dose-escalation allotment, dose-limiting toxicities included prolonged cytopenia after lymphodepletion at the simpler dose in allotment 1 and a single case of hemophagocytic lymphohistiocytosis at the simpler dose in allotment 2 sooner than administering the vaccine.
The researchers also reported eight circumstances of grade 1 or 2 cytokine originate syndrome, which possess been safely managed with tocilizumab when wanted.
Invited discussant Vincent Good adequate. Lam, MD, director of the esophageal most cancers analysis program at Johns Hopkins College in Baltimore, known as the kind “a critical and thrilling arrive for a today growing field.”
Lam highlighted a lot of closing questions about this recent formulation, along side questions referring to the optimum timing, length, and dosing of the mRNA vaccine, as well to the want for a better knowing of tumor microenvironment interactions and mechanisms of resistance that will lead to T-cell exhaustion, better tumor heterogeneity, or antigen loss.
Haanen cautioned now to now not contrivance any vital conclusions but for the reason that see entails a minute affected person population and the results signify early files.
On the opposite hand, general, Haanen concluded that the infusion of the CAR T remedy alone or alongside the vaccine “is safe and holds promise for sufferers with CLDN6-definite cancers.”
The see was backed by BioNTech SE’s subsidiary BioNTech Cell & Gene Therapies GmbH. Haanen is on the scientific advisory board of BioNTech. Lam has bought grant/analysis funding and has equipped consultation products and services for a lot of entities, no longer along side BioNTech.
American Association for Cancer Study (AACR) Annual Assembly 2022: Supplied April 10, 2022.
Neil Osterweil, an award-winning clinical journalist, is a long-standing and frequent contributor to Medscape.
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