LY3381916 / Eli Lilly - LARVOL DELTA

A phase I study of an anti-IDO1 inhibitor (LY3381916) as monotherapy and in combination with an anti-PD-L1 antibody (LY3300054) in patients with advanced cancer (ESMO-IO 2019) - P1a/1b; "LY3381916 is safely administered as monotherapy and in combination with LY3300054. The 240mg dose QD is the RP2D for combination with PD-L1 in expansion cohorts.Legal entity responsible for the study: Eli Lilly and Company. Funding: Eli Lilly and Company."

Clinical • Combination therapy • IO Biomarker • Monotherapy • P1 data • CD8 • IDO1

A Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination With an Anti-PD-L1 Antibody (LY3300054) in Patients With Advanced Cancer. (PubMed, J Immunother) - "These preliminary data suggest an alternative dose level of LY3381916 is needed for the combination with PD-L1 inhibitor. The combination clinical activity was limited in this study."

Clinical • Combination therapy • Journal • Monotherapy • P1 data • Breast Cancer • Fatigue • Hepatology • Immunology • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Systemic Inflammatory Response Syndrome • Triple Negative Breast Cancer • CD8 • IDO1

Identification and characterization of the IDO1 inhibitor LY3381916 (AACR 2018) - "LY3381916 shows no confounding agonism of AHR up to 100 M. Additionally, we characterized LY3381916 in pre-clinical tumor models and demonstrated that it was able to enhance LY3300054, anti-PD-L1 antibody (LY3300054) activity, which was associated with an enhanced T cell response. Basedon these characteristics, LY3381916 is currently being investigated in a Phase I clinical trial. These data suggest further development of LY3381916 may be warranted."

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

A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors (clinicaltrials.gov) - P1a/1b; N=60; Terminated; Sponsor: Eli Lilly and Company; N=175 ➔ 60; Active, not recruiting ➔ Terminated; Study terminated due to strategic business decision by Eli Lilly and Company.

Combination therapy • Enrollment change • Trial termination • Breast Cancer • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer

A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors (clinicaltrials.gov) - P1a/1b; N=175; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Enrollment closed

Side-by-side comparison of small molecule IDO1 inhibitors in biochemical and cell-based assays and development of a IDO1-expressing mouse model to evaluate target modulation (AACR-NCI-EORTC 2019) - "Four small molecule inhibitors are currently investigated in phase III (linrodostat/BMS-986205), phase II (epacadostat/INCB024360) or phase I (MK7162 and LY3381916) clinical trials. Treatment of the B16F10-IDO1 model with epacadostat did not result in a reduction of tumor growth, though epacadostat did induce clear changes in Trp and Kyn in both plasma and tumor tissue. Conclusion Our comparative study of the potencies and selectivities of IDO1 inhibitors, as well as our model for measuring in vivo target modulation, helps to identify strengths and weaknesses of current IDO1 inhibitors, and supports the development of new inhibitors."

IO Biomarker • Preclinical

A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors (clinicaltrials.gov) - P1a/1b; N=175; Recruiting; Sponsor: Eli Lilly and Company; N=290 ➔ 175

Combination therapy • Enrollment change

Tryptophan Metabolism Plays a Central Role in Immunosuppression (AACR 2019) - "Our highly potent, orally available, and CNS penetrant small molecule inhibitor of IDO1 (LY3381916) inhibits this incorporation of tryptophan-derived one carbon units into purines in vitro and in vivo. This activity leads to pre-clinical efficacy and may be an added advantage of inhibiting IDO1 in cancer."

IO Biomarker

A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors (clinicaltrials.gov) - P1a/1b; N=290; Recruiting; Sponsor: Eli Lilly and Company; Initiation date: Nov 2017 ➔ Feb 2018

Combination therapy • Trial initiation date

A Study of LY3381916 Alone or in Combination With LY3300054 in Participants With Solid Tumors (clinicaltrials.gov) - P1a/1b; N=290; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Dec 2020 ➔ Feb 2022; Trial primary completion date: Sep 2019 ➔ Jun 2021

Combination therapy • Trial completion date • Trial primary completion date