LY3321367 / Eli Lilly - LARVOL DELTA

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 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

Beyond PD(L)-1 Blockade in Microsatellite-Instable Cancers: Current Landscape of Immune Co-Inhibitory Receptor Targeting. (PubMed, Cancers (Basel)) - "Ipilimumab (anti-CTLA4) is the only immune checkpoint inhibitor (ICI) non-targeting PD(L)-1 that has been approved so far by the FDA for MSI-H cancer, namely, CRC in combination with nivolumab. Anti-TIM3 antibody LY3321367 showed interesting clinical activity in combination with anti-PDL-1 antibody in patients with MSI-H cancer not previously treated with anti-PD(L)-1...In conclusion, several combination therapies of ICIs and novel strategies are emerging and may revolutionize the treatment paradigm of MSI-H patients in the future. A huge effort will be necessary to find reliable immune biomarkers to personalize therapeutical decisions."

IO biomarker • Journal • Review • Endometrial Cancer • Microsatellite Instability • Oncology • Solid Tumor • BTLA • IL12A • IL5 • LAIR1 • MSI • TIGIT

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 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

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

The molecular basis of blocking the TIM-3 checkpoint with the LY3321367 mAb in cancer immunotherapy (AACR 2019) - P1a/1b; "Consequently, we developed a cell-based assay to demonstrate that LY3321367 completely blocks the binding of soluble human TIM-3 to PS displayed on the surface of Campothecin-treated DO11.10 cells.Our structural results suggest an important role for PS in TIM-3 biology which is blocked by LY3321367. When combined with the partial blocking of GAL-9, the structural data of LY3321367 suggests that the binding sites of PS and GAL-9 may be proximal to each other on TIM-3."

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

New Checkpoint Inhibitors on the Road: Targeting TIM-3 in Solid Tumors. (PubMed, Curr Oncol Rep) - "Early phase clinical trials with different anti-TIM-3 monoclonal antibodies have shown a safe toxicity profile, as cobolimab, LY3321367, or sabatolimab; however, the general antitumor activity remains to be determined and further investigations are needed. However, the TIM-3 pathway is highly complex in terms of non-canonical signaling, broad expression by different immune cells and multiple ligands. Different anti-TIM-3 inhibitors are currently on research, either as monotherapy or in combination with other immunotherapies or chemotherapy, aiming to overcome resistance."

Checkpoint inhibition • IO biomarker • Journal • Review • Oncology • Solid Tumor • HAVCR2

"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/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 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 2021 ➔ Dec 2022

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 Anti-PD-L1 Checkpoint Antibody (LY3300054) Alone and in Combination in Participants With Advanced Refractory Solid Tumors (clinicaltrials.gov) - P1a/1b; N=115; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Jul 2019 ➔ Jul 2020; Trial primary completion date: Jul 2019 ➔ Jul 2020

Combination therapy • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Hepatology • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Melanoma • Microsatellite Instability • Pancreatic Adenocarcinoma • Pancreatic Cancer • Skin Cancer • 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) - P1a/1b; N=215; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Apr 2022 ➔ Dec 2021; Trial primary completion date: Oct 2020 ➔ Jun 2020

Combination therapy • Trial completion date • Trial primary 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) - P1a/1b; N=215; Recruiting; Sponsor: Eli Lilly and Company; N=115 ➔ 215

Combination therapy • Enrollment change • 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) - P1a/1b; N=215; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Jul 2020 ➔ Jul 2021; Trial primary completion date: Jul 2020 ➔ Jan 2020

Combination therapy • Trial completion date • Trial primary 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) - P1a/1b; N=215; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • 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) - P1a/1b; N=205; Recruiting; Sponsor: Eli Lilly and Company; Initiation date: Jun 2016 ➔ Jan 2016

Combination therapy • Trial initiation 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) - P1a/1b; N=205; Recruiting; Sponsor: Eli Lilly and Company; Initiation date: Jan 2016 ➔ Jun 2016

Combination therapy • Trial initiation 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) - P1a/1b; N=215; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: Jul 2021 ➔ Apr 2022; Trial primary completion date: Jan 2020 ➔ Oct 2020

Combination therapy • Trial completion date • Trial primary 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) - P1a/1b; N=100; Recruiting; Sponsor: Eli Lilly and Company; N=205 ➔ 100

Combination therapy • Enrollment change • 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