mipasetamab uzoptirine (ADCT-601)

P1, N=128, Terminated, ADC Therapeutics S.A. | N=260 --> 128 | Trial completion date: Aug 2027 --> Apr 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2026 --> Apr 2025; Sponsor decided to halt further development of ADCT-601

Immunotherapeutic strategies for neuroblastoma must address the potential of epigenetic downregulation of antigen density as a mechanism for immune evasion. We identified several RTKs as candidate MES-specific immunotherapeutic target proteins for the elimination of therapy-resistant cells. We hypothesize that the phenomena of immune escape will be less likely when targeting pan-neuroblastoma cell surface proteins such as B7-H3 and L1CAM, and/or dual targeting strategies that consider both the ADRN- and MES-cell states.

P1, N=260, Active, not recruiting, ADC Therapeutics S.A. | Recruiting --> Active, not recruiting

We identified several receptor tyrosine kinases (RTKs) enriched in MES-dominant samples and showed that AXL targeting with ADCT-601 was potently cytotoxic in MES-dominant cell lines and showed specific anti-tumor activity in a MES cell line-derived xenograft...Several plasma membrane proteins are being developed as immunotherapeutic targets in this disease. Here we define which cell surface proteins are susceptible to epigenetically regulated downregulation during an adrenergic to mesenchymal cell state switch and propose immunotherapeutic strategies to anticipate and circumvent acquired immunotherapeutic resistance.

P1, N=260, Recruiting, ADC Therapeutics S.A. | N=196 --> 260

P1, N=196, Recruiting, ADC Therapeutics S.A. | Phase classification: P1b --> P1

P1b, N=196, Recruiting, ADC Therapeutics S.A. | N=66 --> 196

The purpose of this study was to test a suboptimal single dose of mipasetamab uzoptirine (ADCT-601), an ADC targeting the AXL protein, in combination with ultrasound-induced cavitation in a preclinical mouse model of renal cancer...This was demonstrated for a suboptimal ADC dose, indicating that ultrasound-mediated drug delivery could be used to reduce the administered dose while preserving therapeutic efficacy. These preclinical data warrant further evaluation of this promising combination in the clinic.

P1b, N=66, Recruiting, ADC Therapeutics S.A. | Not yet recruiting --> Recruiting

P1b, N=66, Not yet recruiting, ADC Therapeutics S.A.

Notably, ADCT-601 had antitumor activity in a monomethyl auristatin E-resistant lung-cancer model and synergized with the PARP inhibitor olaparib in a BRCA1-mutated ovarian cancer model. ADCT-601 was well tolerated at doses of up to 6 mg/kg and showed excellent stability in vivo. These preclinical results warrant further evaluation of ADCT-601 in the clinic.