Mylotarg (gemtuzumab ozogamicin)

P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=32 --> 0 | Trial completion date: Dec 2034 --> May 2026 | Initiation date: Dec 2027 --> May 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2032 --> May 2026

P2, N=162, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

The anti-CCRL2 ADC demonstrated strong CCRL2-selective cytotoxicity against cell lines derived from MDS/AML patients with TP53 mutations and erythroid features, surpassing the cytotoxic effects observed with gemtuzumab and PBD-conjugated anti-CD33 and anti-CD123 ADCs...This agent also suppressed the leukemic growth of TP53-mutated MDS/AML cell line xenografts, improving mice survival and decreasing the leukemic burden in patient-derived TP53-mutated MDS/AML xenografts. In conclusion, our study introduces CCRL2 as a potential new therapeutic target in high-risk MDS/AML including TP53-mutated subsets.

To our knowledge, this is the first study to investigate the prognostic impact of the CD33 rs12459419 SNP per se on outcome and survival in adult AML patients treated with chemotherapy without GO. Validation in larger patient cohorts is required to conclusively rule out a prognostic role of the CD33 rs12459419 SNP in AML.

In summary, trem-cel demonstrated safe, rapid, robust engraftment, and GO maintenance was administered without prolonged hematologic toxicity. ClinicalTrials.gov identifier: NCT04849910 .

P2, N=133, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

P3, N=700, Recruiting, University of Birmingham | Active, not recruiting --> Recruiting

P3, N=130, Recruiting, PedAL BCU, LLC | N=98 --> 130

The patient achieved complete remission following the standard 7 + 3 induction chemotherapy regimen for AML with gemtuzumab ozogamicin. This case illustrates the diagnostic challenges posed by concomitant class-defining alterations in hematologic neoplasms and underscores the importance of integrated genomic assessment.

We validated these clinical and molecular findings in an independent validation cohort of 302 NPM1 mut patients enrolled in the acute myeloid leukemia study group (AMLSG) 09-09 clinical trial, which included the administration of all-trans retinoic acid (ATRA) to all patients and a randomization for gemtuzumab ozogamicin. In this cohort, the APL-like immunophenotype was associated with events occurring within the first 15 days but did not influence mortality, likely due to protocol-driven patient selection. Our findings have important clinical implications that warrant the development of studies exploring disease-tailored clinical measures to mitigate the risk of early vascular events, as in current APL management.

P3, N=700, Active, not recruiting, University of Birmingham | Recruiting --> Active, not recruiting

Such inhibition caused cell line-dependent changes in the expression of apoptotic regulators, including BCL-2, MCL-1 and p53 protein, suggesting that cellular context shapes responses to combined treatments. In conclusion, our findings identify BCL-2 and PI3K inhibition as a promising new approach to sensitize AML cells to GO therapy, and highlight the importance of these pathways in determining the cellular response to gemtuzumab ozogamicin.