Mylotarg (gemtuzumab ozogamicin)

P3, N=1186, Recruiting, Children's Oncology Group | Trial completion date: Sep 2027 --> Jun 2029 | Trial primary completion date: Sep 2027 --> Jun 2029

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.

P2, N=100, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

P=N/A, N=165, Recruiting, Pfizer | Trial completion date: Nov 2027 --> Apr 2027 | Trial primary completion date: Nov 2027 --> Apr 2027

For patients entering the course-2 randomisation (n=107) survival was equivalent between standard versus intensified CPX doses (P=0.565).In this population of older patients without known adverse-risk cytogenetics, DAGO2 resulted in superior survival compared to CPX. CPX did not benefit those with MDS-related mutations over DAGO2.

Combining UM171-mediated expansion with adenine base editing (ABE), we precisely disrupted the P67 epitope of CD33, centered on phenylalanine 21, which is essential for gemtuzumab ozogamicin (GO) binding. Ultra-deep exome sequencing and GUIDE-seq revealed minimal off-target activity. Together, these findings establish CD33 P67 epitope-directed base editing as a precise, scalable strategy to generate immunotherapy-compatible, UM171-expanded CB grafts that safely enable GO integration into post-transplant care.

P2, N=50, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2027

P1, N=21, Completed, Uma Borate | Active, not recruiting --> Completed

To date, only antibody-drug conjugates have reached regulatory approval, with gemtuzumab ozogamicin approved in combination with intensive induction and consolidation therapy for newly diagnosed CD33-positive AML...This review will introduce the current immunotherapy platforms under investigation in AML, starting with antibody-based approaches, followed by T-cell redirecting therapies, and culminating in an overview of immune resistance, the bone marrow microenvironment, and strategies toward personalized combinatorial immunotherapy. By synthesizing recent clinical data and mechanistic insights, including those from early CAR and T-cell engager trials, we aim to provide a translational framework for how immunotherapy might still reshape AML care-through integration of immune contexture of the bone marrow environment aiming for rational combinatorial approaches.

We evaluated the safety and efficacy of the combination of daunorubicin, cytarabine (DA), gemtuzumab ozogamicin (GO) and midostaurin (DAGO+m) for younger patients with newly diagnosed FLT3mut AML in the UK NCRI AML19 trial...DAGO2+m will now be evaluated in a randomised study (OPTIMISE-FLT3, ISRCTN 34016918). Trial: ISRCTN78449203.

P2, N=50, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not 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...In conclusion, our study introduces CCRL2 as a potential new therapeutic target in high-risk MDS/AML. Pyrrolobenzodiazepine(PBD)-conjugated anti-CCRL2 ADC shows anti-leukemic effect in MDS/AML models including TP53 -mutated disease without affecting healthy hematopoietic cells supporting that it is a promising candidate for single-agent or combination therapies in high-risk MDS/AML.