lexatumumab (ETR2-ST01)

Furthermore, the cytotoxicity induced by that combination was significantly suppressed by the DR5:Fc chimeric protein, as well as specific inhibitors of caspase‑8, ‑9, ‑6 and ‑3. Taken together, these results indicated that celastrol enhances both TRAIL‑R2‑mediated apoptosis and cytotoxicity by upregulating TRAIL‑R2 and activating the caspase cascade, indicating the possibility of using it in combination with lexatumumab as an innovative therapeutic strategy for treating RCC.

Certain clues of scientific evidence have provided encouraging results about efficacy of these agonistic antibodies (lexatumumab and mapatumumab) against bladder cancer cell lines. Therefore, multipronged approaches consisting of natural products, chemotherapeutics, and agonistic antibodies will realistically and mechanistically provide proof-of-concept for the translational potential of these combinatorial strategies in well-designed clinical trials.

In preclinical assays, BI 905711 demonstrated a potency shift of ̃1000 fold versus the 1st-generation TRAILR2 agonist lexatumumab. Secondary endpoints include PK parameters and OR in pts with measurable disease (phase Ia), and disease control, tumor shrinkage, duration of response, and progression-free survival (phase Ib). Trial enrollment is ongoing, with 33 pts enrolled to date.

P2;N=94 --> 0 | Not yet recruiting --> Withdrawn