P1/2, N=42, Terminated, Genmab | N=110 --> 42 | Trial completion date: Dec 2026 --> Nov 2025 | Recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Nov 2025; Genmab has decided to discontinue the clinical development of GEN1160 due to slow enrolment

Multiple CD70-targeted therapies, including CAR-T and CAR-NK, are under active investigation. Rational combination strategies are emerging to enhance antitumor efficacy.

Noncellular therapies targeting CD70, such as antibody-drug conjugates, monoclonal antibodies, radionuclides, and cytokines, are currently under investigation, with early data showing encouraging results as well. Efforts are already underway to further improve and optimize CD70-based therapies.

Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.

In addition, using immunohistological staining, we found that CD70 was expressed on 10 of 10 patients who had progressed on BCMA targeted therapies (seven who had progressed on belantamab mafodotin, an antibody drug conjugate, three who had progressed on idecabtagene vicleucel, a BCMA CAR-T), suggesting that CD70 could be a viable target in patients who have failed BCMA targeted therapy. In summary, we were able to demonstrate that CD70 can be a feasible target for the treatment of multiple myeloma, including in patients who have failed BCMA targeted therapy. Based on these results, we have initiated a Phase I/II clinical trial (NCT05092451) that is currently recruiting.

PK, immunogenicity, and antitumor activity will also be evaluated. The study is currently enrolling at sites in the US, with future enrollment in China planned.

Conclusions In summary, the highly selective and potent anti-tumor activity in multiple tumor types and wide pre-clinical therapeutic index of ARX305 support clinical evaluation of this next generation anti-CD70 ADC. ARX305 is currently in a phase 1 dose-escalation study in China.

In summary, the highly potent anti-tumor activity in multiple tumor types and wide therapeutic index of ARX305 support clinical evaluation of this next generation anti-CD70 ADC. ARX305 is currently in a Phase 1 dose escalation study in China, and the IND in the United States is open.

CXCR5 is a highly attractive target in hematological malignancies such as DLBCL, MCL, and FL due to high protein expression and almost no expression in healthy tissues. CXCR5-targeting ADC with KSPi payload showed high potency and superiority to other B-cell-targeted ADCs in vitro on a broad range of lymphoma cell lines. VIP924 with a novel legumain-cleavable linker showed activity in in vivo PDX models from lymphoma patients.

Anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting chimeric antigen receptor (CAR) T cell and CAR NK cells show potent activity against EGFR TKI-resistant cells and DTPCs. These results identify CD70 as a therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits clinical investigation.

Although these patients are initially highly sensitive to first or second generation EGFR tyrosine kinase inhibitors (TKIs) including erlotinib or third-generation inhibitors including osimertinib, EGFR TKI-refractory disease inevitably emerges. CD70-targeting approaches including anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting CAR T cell and CAR NK cells showed promising in vitro and in vivo activity against CD70 positive tumor cells and in osimertinib drug-tolerant persister cells. These results identify CD70 as a novel therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits further investigation in the clinic.