The Targeted Pulse: A Spread of Newly Approved Agents, CAR T-Cell Box Warnings, and More

Tovorafenib Gains Accelerated Approval for Pediatric Low-Grade Glioma

Tovorafenib (Ojemda) has received an accelerated approval from the FDA for the management of relapsed or refractory BRAF-altered pediatric low-grade glioma (pLGG). The approval is based on the phase 2 FIREFLY-1 trial (NCT04775485), which evaluated the safety and efficacy of the agent in children, adolescents, and young adults with RAF relapsed or refractory pLGG or advanced solid tumors. Patients included in the FIREFLY-1 trial were aged 6 months to 25 years.

Prior to the approval, there were no approved therapies available for the majority of patients diagnosed with pLGG, which is the most prevalent type of brain tumor found in children.

Nogapendekin Alfa Inbakicept Gains Approval for BCG-Unresponsive NMIBC Carcinoma in Situ

Nogapendekin alfa inbakicept-pmln (N-803; Anktiva) received FDA approval for the management of Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without Ta or T1 disease. The approval was primarily based on findings from the phase 2/3 QUILT 3.032 trial (NCT03022825). The study showed that the agent improved efficacy and safety for patients who failed on prior therapies.

“Not only CIS, but also the papillary tumors at 2 years had around 50% response rates, or 2 to 3 events, so a real significant improvement,” Sam S. Chang, MD, MBA stated in an interview commenting on the study. Chang is professor of the Department of Urology, Patricia and Rodes Hart professor of urologic surgery, and chief surgical officer and chief of the Division of Urologic Oncology at Vanderbilt Ingram Cancer Center in Nashville, TN.

CAR T-Cell Immunotherapies Face FDA Call for Boxed Warnings

For T-cell malignancies on BCMA- or CD19-directed chimeric antigen receptor T-cell therapies, the FDA now requires a boxed warning. The warning is based on investigations that started in November 2023, as well as issued label changes made in January 2024. There are 6 agents this currently affects:

• idecabtagene vicleucel (ide-cel; Abecma),
• lisocabtagene maraleucel (liso-cel; Breyanzi),
• ciltacabtagene autoleucel (cilta-cel; Carvykti),
• tisagenlecleucel (tisa-cel; Kymriah),
• brexucabtagene autoleucel (brexu-cel; Tecartus), and
• axicabtagene ciloleucel (axi-cel; Yescarta).

These therapies, along with all other gene therapy treatments using lentiviral or retroviral vectors, were already flagged with a warning about the risk of developing secondary cancers. To be approved, a 15-year observational safety follow-up, specifically evaluating the risk of secondary malignancies, was required.

Advancing Risk Factor Identification in Papillary Thyroid Microcarcinoma

After a multivariate analysis, which found that factors such as a higher Rad score, younger age, and capsule invasion were independently associated with a higher risk of central lymph node metastasis, researchers created a nomogram. The nomogram yielded promising results and may serve as a useful tool for determining the risk of developing central lymph node metastasis in patients with clinically node-negative papillary thyroid microcarcinoma.

“The 6 feature–based Rad score exhibited a significant association with the risk of [central lymph node metastasis]. Moreover, combining this score with other clinical and US factors, the nomogram provided strong predictive power in the training and validation cohorts. These results suggest that this radiomics-based predictive model is a noninvasive, objective, and reliable tool for the preoperative prediction of [central lymph node metastasis],” authors wrote in the study published in Thyroid Research.

FDA Approves Adjuvant Use of Alectinib in ALK-Positive NSCLC

The FDA approved alectinib (Alecensa) as an adjuvant treatment for patients with ALK-positive non-small cell lung cancer following tumor resection. This approval is specifically for patients whose tumors are at least 4 cm in size or are node positive, as determined by an FDA-approved test. The regulatory decision is based on data from the phase 3 ALINA trial (NCT03456076), which compared the agent to platinum-based chemotherapy.

“With an unprecedented 76% reduction in the risk of disease recurrence or death versus chemotherapy, Alecensa significantly improves upon the standard of care for people with early-stage ALK-positive lung cancer,” said Levi Garraway, MD, PhD. Garraway is chief medical officer and head of Global Product Development at Genentech.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.