LY3415244 / Eli Lilly - LARVOL DELTA

Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors. (PubMed, Clin Cancer Res) - "This TIM-3 and PD-L1 bispecific format was associated with unexpected immunogenicity targeting both arms of the bispecific antibody, resulting in early study termination. Epitope specificity analysis revealed an initial response towards the TIM-3 arm and presence of pre‑existing ADAs to the bispecific molecule in the general population. This experience emphasizes the importance of thorough analyses for pre‑existing ADAs as part of immunogenicity risk assessment of novel antibodies."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

"Looking into Tim3 this morning I see $LLY $ZYME Tim3/PD-1 LY3415244 is terminated, per CTgov; LY3321367 (straight anti-Tim3 MAb) still in play in 2 trials $AZN $NVS $GSK" (@JacobPlieth)

PD-1

A Phase Ia/b study of TIM-3/PD-L1 bispecific antibody in patients with advanced solid tumors. (ASCO 2019) - P1a/1b; "...LY3415244 is a TIM-3/PD-L1 bispecific antibody that has the ability to target and inhibit both TIM-3 and PD-L1 and the potential to overcome primary and acquired anti-PD-(L)1 resistance by a novel mechanism to bridge TIM-3- and PD-L1-expressing cells...The study is currently open to enrollment. Clinical trial information: NCT03752177"

Clinical • IO Biomarker • PD(L)-1 Biomarker

Anti-drug antibodies and drug development: challenges in the immunotherapy era. (PubMed, Clin Cancer Res) - "LY3415244, a novel TIM3-PDL1 bispecific caused neutralizing antidrug antibodies (ADAs) in 12 out of 12 patients and required study termination. Novel approaches are needed to ameliorate and manage this undesirable effect of therapeutic antibodies."

Journal • HAVCR2 • PD-L1

A Study of LY3415244 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=12; Terminated; Sponsor: Eli Lilly and Company; N=117 ➔ 12; Active, not recruiting ➔ Terminated; The study was terminated during dose escalation after a determination was made that the risk:benefit ratio no longer favored continued evaluation.

Clinical • Enrollment change • Trial termination

A Study of LY3415244 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=117; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study of LY3415244 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=117; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Oct 2020 ➔ Oct 2019; Trial primary completion date: Oct 2020 ➔ Oct 2019

Clinical • Trial completion date • Trial primary completion date