Lisocabtagene maraleucel

Bristol Myers Squibb’s Augtyro (repotrectinib) has been granted accelerated approval by the US Food and Drug Administration (FDA) to treat neurotrophic tyrosine receptor kinase (NTRK)-positive tumours. The tyrosine kinase inhibitor (TKI) has been specifically authorised for use in adult and paediatric patients aged 12 years of age and older with tumours that are locally advanced or metastatic, or where surgical resection is likely to result in severe morbidity, who have progressed following treatment or have no satisfactory alternative therapy. Augtyro, which was added to BMS’ oncology portfolio in 2022 through its $4.1bn acquisition of Turning Point Therapeutics, was approved by the FDA last November to treat adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The FDA’s latest decision on the drug was supported by positive results from the phase 1/2 TRIDENT-1 study, which evaluated Augtyro in adults with NTRK-positive solid tumours. At a median follow-up of 17.8 months, 58% of Augtyro-treated patients who had not previously received any TKI treatment had a confirmed objective response rate. In TKI-pretreated patients, with a median follow-up of 20.1 months, the confirmed objective response rate was 50%. After one year of Augtyro treatment, 83% of TKI-naïve responding patients and 42% of TKI-pretreated responding patients were still in response. “NTRK fusion-positive tumours can present challenges in the clinical setting, which is why it is important that we have additional treatment options for these patients,” explained TRIDENT-1 global trial lead, Alexander Drilon, Memorial Sloan Kettering Cancer Center. He continued: “The FDA approval of [Augtyro] adds an important tool to our toolbox, offering oncologists a next-generation TKI that can be used across a broad range of NTRK fusion-positive solid tumours for both TKI-naïve and TKI-pretreated patients.” The decision comes just two weeks after the FDA approved BMS’ CAR T cell therapy Breyanzi (lisocabtagene maraleucel) to treat adults with relapsed or refractory mantle cell lymphoma who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor. The company also recently received approval from the European Commission for Opdivo (nivolumab) as part of a combination treatment for adults with unresectable or metastatic urothelial carcinoma.

Pictured: 3D illustration of a CAR-T cell attacking a cancer cell/iStock, Meletios Verras Despite warnings about the drug class from the FDA, a large study led by Stanford Medicine has found that CAR-T cell therapies carry only a low risk of secondary malignancies. The results, published Wednesday in The New England Journal of Medicine, come from a review of 724 patients who had undergone CAR-T therapies at Stanford Health Care between 2016 and 2024. Overall, the study found that secondary cancers arose in approximately 6.5% of patients over a median follow-up period of three years. According to Stanford’s announcement on Wednesday, this incidence rate was “roughly similar” to patients who had been treated instead with stem cell therapy. The study identified one patient who died due to a secondary T-cell cancer, though Stanford researchers contend this was likely caused by the immunosuppression associated with CAR-T therapies, rather than a mis-insertion of the gene for the CAR construct during the preparation of the treatment. Deep profiling of both the original and secondary cancers found that they had “distinct immunophenotypes and genomic pro ” according to researchers, suggesting that that the CAR-T therapy was not responsible for the secondary malignancy. “These results may help researchers focus on the immune suppression that can precede and often follows CAR-T therapy,” David Miklos, co-senior author of the study and chief of bone marrow transplantation and cell therapy at Stanford, said in a statement. Understanding how immunosuppression aggravates cancer risk after CAR-T treatment is especially important “as the CAR-T cell field pivots from treating high-risk, refractory blood cancers to lower risk, but clinically important, disorders including autoimmune diseases,” Miklos said. Stanford’s findings echo that of Penn Medicine, which in January 2024 published a paper in Nature Medicine that also found a low risk of secondary cancers after CAR-T treatment. The Penn researchers used a smaller sample size—449 patients—but their figures were similar: Over a median follow-up of 10.3 months, only 16 patients developed secondary cancers, most of which were solid tumors such as skin and prostate cancer. There was only one case of secondary T-cell lymphoma, which showed only “very low” levels of the CAR transgene. The respective findings from Stanford and Penn could help allay some concerns about the safety of CAR-T therapies. In November 2023, the FDA announced that it was investigating the drug class after it identified cases of secondary malignancies in patients who had received approved CAR-T products. The probe pushed the regulator in April 2024 to require a class-wide black box warning flagging the risk. All six commercially available CAR-T therapies were impacted including Gilead’s Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel), Bristol Myers Squibb’s Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Novartis’ Kymriah (tisagenlecleucel) and Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel). Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.