The Targeted Pulse: FDA Actions and Trial Analyses

Welcome to this week's edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw FDA decisions, learned about care-changing trial data, and heard from expert clinicians in the field. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

FDA Grants Orphan Drug Status to Novel CD33-Directed Immunotherapy for AML

The FDA has granted orphan drug designation to M2T-CD33 (LTI-214), an investigational myeloid-targeted immunotherapy from Leukogene Therapeutics, for treating acute myeloid leukemia (AML).

This novel agent is designed to selectively eliminate CD33-positive leukemic blasts and stem cells, which are the drivers of disease progression in AML. M2T-CD33 is a myeloid-targeted treatment being developed in response to this need, with the objective of reducing toxicities while delivering in efficacy. The agent utilizes Leukogene Therapeutics’ proprietary M2T™ platform, consisting of a high affinity MHCII binding protein conjugated to tumor associated antigens.The platform is designed to selectively eliminate CD33-positive leukemic blasts and stem cells by generating a potent T and B cell response against the selected antigen. Preclinical data showed robust anti-leukemic activity, a significant reduction in tumor burden, and a favorable safety profile with no evidence of cytokine-release syndrome.

Dr Capdevila on "Practice-Changing" COMPETE Trial in GEP-NETs

Dr Jaume Capdevila highlighted the phase 3 COMPETE trial results as "practice-changing" for patients with grade 1 or grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The study compared the radioligand therapy ITM-11 (¹⁷⁷Lu-edotretide) against the targeted therapy, everolimus.

ITM-11 met its primary end point, demonstrating a statistically and clinically significant improvement in progression-free survival, with a median of 23.9 months vs 14.1 months for everolimus. It also showed a higher objective response rate. Critically, ITM-11 demonstrated a favorable safety profile with fewer treatment-related adverse events and no observed cases of leukemia in the long-term follow-up, positioning it to potentially become a new standard treatment option.

FDA Approves Subcutaneous Daratumumab for Smoldering Multiple Myeloma

The FDA has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) as the first and only treatment for adults with high-risk smoldering multiple myeloma.

The approval is based on the phase 3 AQUILA trial, which compared the subcutaneous therapy against active monitoring. Daratumumab significantly met its primary end point, reducing the risk of progression to active multiple myeloma or death by 51%. The 5-year progression-free survival rate was 63.1% in the treatment arm vs 40.7% in the monitoring arm. This milestone establishes a new paradigm for earlier intervention, moving beyond the traditional "watch and wait" approach for this high-risk patient population.

Two Decades of Global Cancer Clinical Trial Development Marked by Disparities

A 20-year analysis of cancer clinical trial development in low- and middle-income countries (LMICs) revealed significant disparities, despite a global increase in research. The study, published in Cancer, examined 16,977 trials between 2001 and 2020. East Asian countries like China and South Korea saw the greatest growth, often correlating with strong economic development.

However, the correlation was inconsistent: some rapidly growing economies in South and Southeast Asia (eg, India, Indonesia) showed limited trial growth, while some countries in the Americas (eg, Argentina, Brazil) saw more trials despite economic stagnation. The findings suggest that economic growth is a contributor, but not the sole determinant, of cancer clinical research output in LMICs, underscoring the need for enhanced global support initiatives.

Tiragolumab Triplet Misses PFS in Untreated HCC

The phase 3 IMbrave152/SKYSCRAPER-14 study found that adding tiragolumab (MTIG7192A) to the standard regimen of atezolizumab (Tecentriq) and bevacizumab (Avastin) did not significantly improve outcomes for patients with previously untreated locally advanced or metastatic hepatocellular carcinoma.

The triplet combination missed the coprimary end point of investigator-assessed progression-free survival (PFS). The median PFS was nearly identical in both the tiragolumab arm (8.3 months) and the placebo arm (8.2 months). Overall survival data remain immature, and the findings reinforce the established efficacy of the atezolizumab-bevacizumab doublet as the front-line benchmark.