Iomab-ACT is being studied with Yescarta (FDA-approved commercial CAR-T) for r/r DLBCL.
On January 10, 2025, clinicaltrials.gov was updated with the new Actinium Pharmaceutical trial to pre-treat patients with Iomab-ACT before CAR-T for r/r DLBCL. Diffuse large B-cell lymphoma (DLBCL) is a type of blood cancer that affects B cells, a type of white blood cell. DLBCL is a type of lymphoma, while AML is a type of leukemia.
Normally, Yescarta patients are pretreated with Fludarabine/Cyclophosphamide (Flu/Cy). This presents an interesting discussion regarding the FDA recommendation for a confirmatory trial with Iomab-B Flu/Cy/TBI vs. Flu/Cy/TBI to confirm if there is a survival benefit. Iomab-ACT is a lesser dose of Iomab-B; 50 mCi and an average 664 mCi respectively (~13x less dosage).
Iomab-ACT + Yescarta trial is planned for safety and dosing trials during 2025 (est. starting enrollment April 1, 2025) and results are expected by 2H2025. If these results prove successful, a following comparison trial of Iomab-ACT/CAR-T vs. Flu/Cy/CAR-T will be conducted to determine modified event-free survival (primary) and response rate, overall survival, and progression-free survival (secondary). This trial could serve two benefits.
1) demonstrate that Iomab-ACT prior to CAR-T is better than current pre-treatments. With the ongoing development of AML CAR-T, this could be the next step toward a cure for AML. Current treatments use preconditioning, bone marrow transplant, and post-treatment maintenance.
(2) further support the Phase 3 SIERRA results that the higher dosage Iomab-B is clinically beneficial in an AML setting.
FDA Inconsistencies with Drug Reviews/Approvals and a Need for FDA CDER Staff Change.
September 23, 2024.
"Survival results for AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan in TROPION-Breast01 did not achieve statistical significance versus chemotherapy"
https://www.astrazeneca.com/media-centre/press-releases/2024/datopotamab-deruxtecan-final-overall-survival-results-reported-in-patients-with-metastatic-hr-positive-her2-low-or-negative-breast-cancer-in-tropion-breast01-phase-iii-trial.html
January 17, 2025
"FDA approves AstraZeneca and Daiichi Sankyo’s ADC for breast cancer despite lack of survival benefit"
https://endpts.com/fda-approves-astrazeneca-and-daiichi-sankyos-adc-for-breast-cancer-despite-lack-of-survival-benefit/
This example demonstrates the inconsistencies of the FDA CDER recommendations. AstraZeneca's trial did not demonstrate statistical significance in overall survival, however, was still approved.
Why did they not receive a recommendation like Actinium and Cellectar? Or why did they not give AstraZeneca a CRL like they did to Vanda Pharma for not achieving statistical significance in their trials?
In August 2024, the FDA CDER told Actinium not to submit the BLA and recommended another confirmatory trial, further delaying patient access to Iomab-B. This was despite Iomab-B demonstrating it had met the primary endpoint in the trial and demonstrated an event-free and overall survival benefit in the subanalysis of the cross-over and control arms. 104 patients were administered Iomab-B vs control with a median Overall Survival better than the control.
As mentioned in a prior post, 2 other companies experienced similar delays and roadblocks from the FDA despite achieving their study endpoints and demonstrating clinical efficacy.
This further adds another vignette to justify the appeal for the FDA to accept the results of Iomab-B. This is also the examples we need to support change and get patients Early Access to Iomab-B upon submission for FDA review.
Thank you for your continued support of this petition. Your support demonstrates how many people are negatively affected by inconsistent FDA CDER recommendations and decisions not motivated by scientific outcomes. It also helps others, who haven't been affected by AML, understand why it is so important to give people access to life-saving medicine.