EnaV had an acceptable safety profile; however, because the evaluation of antitumor activity did not show clinically meaningful responses, clinical development of EnaV was discontinued.

P2, N=85, Completed, BioAtla, Inc. | Active, not recruiting --> Completed | N=240 --> 85

P1/2, N=245, Completed, BioAtla, Inc. | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Jan 2025

P1/2, N=300, Active, not recruiting, BioAtla, Inc. | Trial completion date: Jan 2025 --> Jun 2025

Furthermore, in nonhuman primates, mecbotamab vedotin demonstrated excellent tolerability at doses of up to 5 mg/kg and maintained linker-payload stability in vivo. These findings indicate that mecbotamab vedotin has the potential to be a robust and less toxic therapeutic agent, offering promise as a treatment for patients with AXL-positive cancers.

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.

P1/2, N=300, Active, not recruiting, BioAtla, Inc. | Recruiting --> Active, not recruiting

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

P2, N=240, Active, not recruiting, BioAtla, Inc. | Recruiting --> Active, not recruiting

P2, N=60, Recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jun 2024 --> Dec 2024

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.