lodapolimab (LY3300054) / Eli Lilly - LARVOL DELTA

A Study of LY3200882 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=223 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Solid Tumor

A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=164 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Breast Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Microsatellite Instability • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Skin Cancer • Solid Tumor • ER • HER-2 • MSI • PGR

A Study of LY3200882 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=223 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Oncology • Solid Tumor

A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=215 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Mar 2024 ➔ Jul 2024

Combination therapy • Metastases • Trial completion date • Breast Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Microsatellite Instability • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Skin Cancer • Solid Tumor • ER • HER-2 • MSI • PGR

A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=215 | Active, not recruiting | Sponsor: Eli Lilly and Company | Phase classification: P1a/1b ➔ P1 | Trial completion date: Dec 2023 ➔ Mar 2024

Combination therapy • Metastases • Phase classification • Trial completion date • Breast Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Microsatellite Instability • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Skin Cancer • Solid Tumor • ER • HER-2 • MSI • PGR

A Study of LY3200882 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=223 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2023 ➔ Aug 2024

Trial completion date • Oncology • Solid Tumor

A Study of LY3321367 Alone or With LY3300054 in Participants With Advanced Relapsed/Refractory Solid Tumors (clinicaltrials.gov) - P1a/1b | N=209 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Aug 2023

Combination therapy • Metastases • Trial completion • Trial completion date • Oncology • Solid Tumor

Efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient advanced pancreatic adenocarcinoma: An AGEO European Cohort. (ASCO 2023) - "Nineteen pts received pembrolizumab, 8 received nivolumab, 1 received lodapolimab and 3 received ipilimumab/nivolumab (ipi/nivo). This retrospective analysis suggests that ICIs are effective and well tolerated in pts with MSI/dMMR advanced PDAC. Hence, our work supports the use of PD-1 inhibition in this group of pts with high unmet medical need."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • Mismatch repair • Gastrointestinal Cancer • Genetic Disorders • Immune Modulation • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MLH1 • MSH2 • MSH6 • PMS2

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 Ia/Ib study of an anti-TIM-3 antibody (LY3321367) monotherapy or in combination with an anti-PD-L1 antibody (LY3300054): Interim safety, efficacy, and pharmacokinetic findings in advanced cancers. (ASCO-SITC 2019) - P1a/1b; "LY3321367 is well tolerated as a monotherapy and in combination with LY3300054. The RP2D for LY3321367 combination therapy is 1200 mg IV infusions Q2W for cycles 1-2; 600 mg infusions Q2W starting at cycle 3 onward."

Clinical • Combination therapy • Monotherapy • P1 data • PK/PD data

A phase Ia/Ib study of an anti-TIM-3 antibody (LY3321367) monotherapy or in combination with an anti-PD-L1 antibody (LY3300054): Interim safety, efficacy, and pharmacokinetic findings in advanced cancers. (ASCO-SITC 2019) - P1a/1b; "LY3321367 is well tolerated as a monotherapy and in combination with LY3300054. The RP2D for LY3321367 combination therapy is 1200 mg IV infusions Q2W for cycles 1-2; 600 mg infusions Q2W starting at cycle 3 onward."

Clinical • Combination therapy • Monotherapy • P1 data • PK/PD data

Preclinical characterization of the anti-PD-L1 monoclonal antibody LY3300054 (AACR 2018) - P1a/1b; "The biological activity of LY3300054 on T cells was also shown to be enhanced by co-administration of anti-CTLA4 mAb (ipilimumab) in MLR. A mutational strategy based on integrating the PD-1/PD-L1 structure data with the orthologous sequence data of PD-L1 has identified a residue on PD-L1, which is part of the PD-L1/PD-1 interface, that is critical for the species specificity of LY3300054.This study demonstrates that LY3300054 is novel anti-PD-L1 monoclonal antibody, capable of potently enhancing human T cell function both in vitro and in vivo, and provides previously not described insights into the effects of PD-L1 blockade on the intra- and extra-tumoral immune response. LY3300054 is currently under clinical evaluation in monotherapy and combination with other therapeutic modalities in multiple tumor types."

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

A Study of Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov) - P1a/1b | N=215 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2022 ➔ Dec 2023

Combination therapy • Trial completion date • Breast Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Hepatology • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Microsatellite Instability • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Skin Cancer • Solid Tumor • ER • HER-2 • MSI • PGR

A Study of LY3321367 Alone or With LY3300054 in Participants With Advanced Relapsed/Refractory Solid Tumors (clinicaltrials.gov) - P1a/1b | N=275 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2022 ➔ Dec 2023

Combination therapy • Trial completion date • Oncology • Solid Tumor

A Study of LY3200882 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=223 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2022 ➔ Aug 2023

Trial completion date • Oncology • Solid Tumor

An Insight of RuBisCO Evolution through a Multilevel Approach. (PubMed, Biomolecules) - "Likewise, an increase in the flexibility of the loop structure between αB and βC, as well as Lys330 (form II) and Lys322 (form III) of loop 6, is important to increase photosynthetic efficiency. Thus, the cross-correlation dynamics analysis showed changes in the direction of movement of the secondary structures in the three isoforms. Finally, key amino acid residues related to the flexibility of the RuBisCO structure were indicated, providing important information for its enzymatic engineering."

Journal

First-In-Human Phase I Study of a Next-Generation, Oral, Transforming Growth Factor-Beta Receptor 1 Inhibitor, LY3200882 in Patients with Advanced Cancer. (PubMed, Clin Cancer Res) - P1 | "LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in PC. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced PC are warranted."

Clinical • Journal • P1 data • Brain Cancer • Cardiovascular • Gastrointestinal Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Phase 1 combination study of the CHK1 inhibitor prexasertib (LY2606368) and anti-PD-L1 antibody LY3300054, in patients with high-grade serous ovarian cancer and other advanced solid tumors (SITC 2019) - "Full-dose prexasertib in combination with immune checkpoint blockade is tolerable and has preliminary clinical activity in patients with HGSOC with durable responses. An expansion cohort in this population is currently being enrolled utilizing schedule B. Comprehensive characterization of the immune microenvironment will be performed in paired tumor biopsies, with attention to pharmacodynamic proof-of-mechanism endpoints, including T cell infiltration and PD-L1 expression and their correlation with the induction of DNA damage. Additionally, immune signatures will be correlated with genomic profile and response duration."

Clinical • IO Biomarker • P1 data • PD(L)-1 Biomarker

The positive correlation between baseline absolute eosinophil count (AEC) in blood and clinical benefit to PD-(L)1 inhibition monotherapy (SITC 2019) - "LY3300054 was well-tolerated and demonstrated antitumor activity in patients with MSI-H solid tumors; combination expansions are ongoing."

Clinical • IO Biomarker • Monotherapy • MSi-H Biomarker • PD(L)-1 Biomarker

Interim safety and clinical activity in patients (pts) with advanced refractory solid tumors from a phase Ia/b study investigating the novel anti-PD-L1 antibody (LY3300054) administered alone or in combination with other agents (AACR 2018) - P1a/1b; "This study (NCT02791334) will assess the safety, tolerability and efficacy of LY as monotherapy and in combination with ramucirumab (R), abemaciclib (A) and merestinib (M). LY alone or in combination with R or M appears to be well tolerated and demonstrated preliminary antitumor activity in pts with advanced solid tumors. The PK characteristics of LY support Q2W, Q3W, and possibly the Q4W dosing regimens."

Clinical • Combination therapy • IO Biomarker • P1 data • PD(L)-1 Biomarker • Esophageal Cancer • Hematological Malignancies • Pancreatic Cancer

A phase 1a/b study investigating novel anti-PD-L1 antibody (LY3300054): interim safety and clinical activity in patients with advanced cancers. (SITC 2018) - P1a/1b; "Preliminary biomarker analysis, including but not limited to, PD-L1 and CD8 expression and circulating markers will be presented. Conclusions LY3300054 was well-tolerated and demonstrated antitumor activity in patients with MSI-H solid 861 tumors; combination expansions are ongoing."

Clinical • IO biomarker • MSi-H Biomarker • P1 data • PD(L)-1 Biomarker • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor

A phase Ia/Ib study of an anti-TIM-3 antibody (LY3321367) monotherapy or in combination with an anti-PD-L1 antibody (LY3300054): Interim safety, efficacy, and pharmacokinetic findings in advanced cancers. (ASCO-SITC 2019) - P1a/1b; "LY3321367 is well tolerated as a monotherapy and in combination with LY3300054. The RP2D for LY3321367 combination therapy is 1200 mg IV infusions Q2W for cycles 1-2; 600 mg infusions Q2W starting at cycle 3 onward."

Clinical • Combination therapy • Monotherapy • P1 data • PK/PD data

A Study of LY3321367 Alone or With LY3300054 in Participants With Advanced Relapsed/Refractory Solid Tumors (clinicaltrials.gov) - P1a/1b; N=275; Active, not recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Dec 2021 ➔ Dec 2022

Combination therapy • Trial completion date • Oncology • Solid Tumor

Safety and antitumor activity of α-PD-L1 antibody as monotherapy or in combination with α-TIM-3 antibody in patients with microsatellite instability-high/mismatch repair-deficient tumors. (PubMed, Clin Cancer Res) - "LY3300054 monotherapy and combined LY3300054/anti-TIM-3 had manageable safety profiles. Both regimens showed promising clinical activity against PD-1/PD-L1 inhibitor-naïve MSI-H/dMMR tumors. The combination had limited clinical benefit in patients with PD-1/PD-L1 inhibitor-resistant/refractory MSI‑H/dMMR tumors."

Clinical • Combination therapy • Journal • Mismatch repair • Monotherapy • Immune Modulation • Inflammation • Oncology • Solid Tumor • HAVCR2 • MSI

A Study of LY3200882 in Participants With Solid Tumors (clinicaltrials.gov) - P1; N=223; Active, not recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Sep 2021 ➔ Dec 2022

Clinical • Trial completion date • Oncology • Solid Tumor