FDA Grants Breakthrough Status to ICT01 Plus Venetoclax/Azacitidine in AML

The FDA has granted breakthrough therapy designation (BTD) to ICT01 (IPN60340), an investigational anti-BTN3A antibody, in combination with venetoclax (Venclexta) and azacitidine (ven-aza) for first-line treatment of acute myeloid leukemia (AML).¹

The designation, which specifically applies to patients aged 75 years or older deemed unfit for treatment with intensive chemotherapy due to comorbidities, marks a promising development in this patient population for whom limited treatment options currently exist.

“This [BTD] recognizes both the urgent need for new treatment options for people living with [AML] and the promising data seen so far in the development program for [ICT01],” said Christelle Huguet, PhD, external vice president and head of R&D at Ipsen Pharma, in a news release.¹ “We look forward to working closely with the FDA as we advance to the next stage of clinical development and continue to deliver medicines with the potential to be transformative to people living with cancer.”

ICT01 previously received orphan drug designation from the FDA and European Medicines Agency (EMA) in July 2025. In September 2024, the FDA also granted fast track designation to the ICT01 combination for the indication.

Mechanism of Action

ICT01 is a humanized monoclonal antibody directed against BTN3A, an immune-regulatory molecule expressed across a broad range of cancers. The agent is differentiated from other AML immunotherapies in that does not function as a checkpoint inhibitor, but rather activates T cells directly.

“With ICT01, instead of being a checkpoint inhibitor, it activates γ9δ2 T cells by binding to BTN3A and bypassing the physiological mode of activation. This leads to γ9δ2 T-cell activation and direct cytotoxicity against leukemia,” explained Abhishek Maiti, MD, The University of Texas MD Anderson Cancer Center, in a 2025 interview with Targeted Oncology. “These cells, being part of the innate immune system, also influence other immune bystanders like [natural killer (NK)] cells [and] CD4/CD8 T cells to remodel the immune microenvironment and generate a broader antileukemia effect.”

Combined with ven-aza, ICT01 has demonstrated synergistic antileukemic activity by enhancing immune-mediated cytotoxicity while leveraging the cytoreductive effects of standard therapy.

“There are multiple layers of synergy between ICT01 and azacitidine and venetoclax. There's synergy between azacitidine and ICT01, venetoclax and ICT01, and also between azacitidine and venetoclax itself,” Maiti continued. “Additionally, azacitidine and venetoclax lead to cytoreduction and eradication of leukemia, improving the effector-to-target ratio. That is, we have more activated immune cells and fewer leukemia cells, which further enhances the synergy with ICT01.”

Clinical Foundation and Next Steps: EVICTION Trial

The BTD is supported by preliminary data from the single-arm phase 1/2 EVICTION trial (NCT04243499), a first-in-human clinical evaluation of ICT01’s efficacy and safety in patients newly diagnosed with AML.² Patients were randomized 1:1 to receive standard dosing of ven-aza plus either a low (10 mg) or high (75 mg) dose of ICT01 on day 1 of each cycle.

In the latest update from the trial at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, treatment with the combination showed high rates of response relative to rates seen with historical standard of care treatments.³ Of 54 efficacy-evaluable patients, those receiving the low dosage achieved a complete remission (CR) rate of 68% (95% CI, 51%–82%) and complete remission with incomplete count recovery (CRi) rate of 84% (95% CI, 69%–94%), while those receiving the high dosage achieved a 44% CR (95% CI, 20%–70%) and 69% CRi (95% CI, 41%–89%). These outcomes were accompanied by a favorable safety profile and early signs of durability.

With these data, the sponsor plans to engage with the FDA regarding the design of a future phase 2/3 study to further ICT01’s development in the coming months.

REFERENCES

1. U.S. FDA grants Ipsen’s IPN60340 (ICT01) breakthrough therapy designation in first-line unfit acute myeloid leukemia. News release. Ipsen Pharma. January 13, 2026. Accessed January 14, 2026. https://tinyurl.com/4umv3nc4

2. First-in-human study of ICT01 in patients with advanced cancer (EVICTION). ClinicalTrials.gov. Updated December 18, 2025. Accessed January 14, 2026. https://www.clinicaltrials.gov/study/NCT04243499

3. Garciaz S, Dumas PY, Peterlin P, et al. γ9δ2 T-cell (γ9δ2TC) activation with ICT01 and azacitidine-venetoclax (Aza-Ven) induces high rates of remission and overall survival in patients with newly diagnosed (ND) acute myeloid leukemia (AML): Results from the phase 1/2 study eviction. Blood. 2025;146(Supplement 1):652-652. doi: 10.1182/blood-2025-652