MK-2118 / Merck (MSD) - LARVOL DELTA

Chemoenzymatic synthesis of STING activators (ACS-Fall 2025) - "In this presentation, we will describe the development of biocatalytic processes in the manufacturing of two potent stimulator of interferon gene (STING) activators, ulevostinag and MK-2118. To enable its sustainable synthesis, we demonstrated a 4-step chemoenzymatic process leveraging an evolved enoate-reductase to generate MK-2118 in high chiral purity. Overall, we've demonstrated the exquisite chemo- and enantioselectivity of biocatalysts towards the development of sustainable processes to two novel STING agonists."

STING

Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas. (PubMed, Clin Cancer Res) - P1 | "IT MK-2118 ± pembrolizumab and SC MK-2118 plus pembrolizumab had manageable toxicity and limited antitumor activity. IT but not SC administration demonstrated systemic immune effects."

Journal • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • IL6 • STING

Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas (Clin Cancer Res) - P1 | N=140 | NCT03249792 | Sponsor: Merck Sharp & Dohme LLC | "140 patients were enrolled (arm 1, n=27; arm 2, n=57; arm 4, n=56). Grade 3/4 treatment-related adverse events occurred in 22%, 23%, and 11% of patients, respectively, but no maximum tolerated dose was identified up to MK-2118 20,000, 15,000, and 150,000 µg across the 3 arms. Dose-dependent increases in MK-2118 systemic exposure were observed following IT and SC administration. Objective responses were seen in 0%, 6%, and 4% of patients, respectively."

P1 data • Lymphoma • Solid Tumor

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1 | N=140 | Terminated | Sponsor: Merck Sharp & Dohme LLC | Completed ➔ Terminated; Business Reasons

Combination therapy • Metastases • Monotherapy • Trial termination • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • CD4

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1 | N=140 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD4

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1 | N=160 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: May 2023 ➔ Jan 2023 | Trial primary completion date: May 2023 ➔ Jan 2023

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD4

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1 | N=160 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2022 ➔ May 2023 | Trial primary completion date: Oct 2022 ➔ May 2023

Combination therapy • Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD4

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1 | N=160 | Recruiting | Sponsor: Merck Sharp & Dohme Corp. | Trial completion date: Jun 2022 ➔ Oct 2022 | Trial primary completion date: Jun 2022 ➔ Oct 2022

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD4

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1; N=135; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Trial completion date: Feb 2021 ➔ Apr 2022; Trial primary completion date: Feb 2021 ➔ Apr 2022

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Hepatocellular Cancer • Liver Cancer • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1; N=135; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Trial completion date: Jul 2020 ➔ Feb 2021; Trial primary completion date: Jul 2020 ➔ Feb 2021

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date

Study of MK-2118 Administered as Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab (MK-3475) or by Subcutaneous Injection in Combination With Pembrolizumab in the Treatment of Adults With Advanced/Metastatic Solid Tumors or Lymphomas (MK-2118-001) (clinicaltrials.gov) - P1; N=135; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Trial completion date: Oct 2021 ➔ Jul 2020; Trial primary completion date: Oct 2021 ➔ Jul 2020

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date