BAY 2862789 / Bayer, German Cancer Research Center - LARVOL DELTA

Bayer has cleared out four cancer candidates from its early-stage pipeline, including a STAT3 inhibitor acquired as part of its buyout of Vividion Therapeutics. (FierceBiotech) - "Vividion and Bayer 'made the strategic decision to discontinue the development' of VVD-130850 'based on the totality of the data, which includes safety, PK/PD and activity of the drug,'...The program consisted of a DGK-alpha inhibitor dubbed BAY 2862789 along with a DGKzeta Inhibitor called BAY 2965501....The final cancer drug thrown on the scrap heap was an anti-human CCR8 antibody called BAY 3375968 or lanerkitug."

Discontinued • P1 data • Colorectal Cancer • Melanoma • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Treatment with Diacylglycerol Kinase (DGK) Alpha specific inhibitor BAY2862789 exhibits combination potential with DGK zeta inhibition in biomarker assays during FIH monotherapy Trial (SITC 2025) - P1 | "Accordingly, ex vivo assays performed on a subset of patients (n=>10), including the addition of BAY2965501, demonstrated synergistic elevation in IFNγ and IL2 production on-treatment compared to baseline.Conclusions Specific inhibition of DGKα by BAY2862789 alone does not lead to substantial immune modulation in patients, despite reaching sufficient exposure to synergize with BAY2965501 in ex vivo assays. Data suggests that BAY2862789 should be combined with DGKζ inhibition to achieve the greatest T cell activation in patients."

Biomarker • Biomarker assay • First-in-human • IO biomarker • Monotherapy • Oncology • IFNG • IL2

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Bayer | N=69 ➔ 45 | Active, not recruiting ➔ Completed

Enrollment change • First-in-human • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=69 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Optimal enhancement of anti-tumor T-cell immunity through the combined use of selective DGK zeta and DGK alpha inhibitors (CIMT 2025) - "We previously presented the discovery and pharmacology of the DGKζ-selective inhibitor BAY 2965501 (5). In parallel, we developed the DGKα-selective inhibitor BAY2862789, and analyzed its impact on T-cell activation and anti-tumor immunity, both as single agent and in conjunction with DGKζ inhibition, PDL1-blockade and/or depletion of CCR8-positive T-regulatory cells (6)... The availability of DGKζ and DGKα selective inhibitors allows for hypothesis-driven pharmacology and toxicology studies, and – in combination with the forthcoming single-agent patient exposure data - for a rationally designed dual-agent clinical study."

Infectious Disease • Oncology • CCR8 • TGFB1

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=69 | Recruiting | Sponsor: Bayer | N=102 ➔ 69 | Trial completion date: Mar 2027 ➔ Jul 2025 | Trial primary completion date: Mar 2027 ➔ Jul 2025

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

DGKalpha inhibitor BAY 2862789 FiH trial in advanced solid cancers (ChiCTR) - P1 | N=81 | Sponsor: Jilin Cancer Hospital; Jilin Cancer Hospital

New P1 trial • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Melanoma • Mucosal Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CD4 • EGFR

Optimal enhancement of anti-tumor T-cell immunity through the combined use of selective DGK zeta and DGK alpha inhibitors (SITC 2024) - "Further experimental evidence suggests that dual DGKα/ζ inhibition may result in enhanced T-cell activation compared to selective inhibition alone.1–4 We previously presented the discovery and pharmacology of the DGKζ-selective inhibitor BAY 2965501.5 In parallel, Bayer has developed the DGKα-selective inhibitor BAY2862789, and analyzed its impact on T-cell activation and anti-tumor immunity, both as single agent and in conjunction with DGKζ inhibition, PDL1-blockade and/or depletion of CCR8-positive T-regulatory cells.6 First-in-human clinical trials with selective DGK inhibitors are currently ongoing.7–8 Methods and Results Both inhibitors are human/mouse cross-reactive compounds that enhance in vitro T-cell activation and T-cell mediated tumor cell killing. The model now offers the opportunity to identify optimal combinations that pair maximal enhancement of T-cell immunity with minimal probability for on- and off-target adverse events. Conclusions The availability of..."

Oncology • CCR8 • TGFB1

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=102 | Recruiting | Sponsor: Bayer | Trial primary completion date: Jul 2025 ➔ Mar 2027

Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=102 | Recruiting | Sponsor: Bayer | N=74 ➔ 102

Enrollment change • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=74 | Recruiting | Sponsor: Bayer | Trial completion date: Oct 2026 ➔ Mar 2027 | Trial primary completion date: Feb 2026 ➔ Jul 2025

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=74 | Recruiting | Sponsor: Bayer | Trial completion date: Apr 2026 ➔ Oct 2026 | Trial primary completion date: Oct 2025 ➔ Feb 2026

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • IFNG • IL2

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=74 | Recruiting | Sponsor: Bayer | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • IFNG • IL2

A First-in-human Study to Learn How Safe the Study Treatment BAY2862789 is, to Find the Best Dose, How it Affects the Body, What Maximum Amount Can be Given, How it Moves Into, Through and Out of the Body, and How it Acts on Different Tumors in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=74 | Not yet recruiting | Sponsor: Bayer

Metastases • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • IFNG • IL2