DAX-0,11 % EUR/USD-0,75 % Gold+0,65 % Öl (Brent)-0,04 %

First Presentation of Early Data for Merck’s Investigational STING Agonist (MK-1454) in Patients with Advanced Solid Tumors or Lymphomas at ESMO 2018 Congress

Nachrichtenquelle: Business Wire (engl.)
20.10.2018, 15:00  |  850   |   |   

Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentation of preliminary data from a Phase 1 clinical trial evaluating MK-1454, an investigational STING (stimulator of interferon genes) agonist, as monotherapy and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with advanced solid tumors or lymphomas. MK-1454 is one of more than 20 novel investigational immuno-therapeutic candidates Merck is evaluating as part of its broad oncology pipeline. The findings for MK-1454 were accepted as a late-breaking abstract and are being presented today in a poster discussion session at the ESMO 2018 Congress (Abstract #LBA15).

“Merck is advancing a broad pipeline focused on the development of novel therapies with potential to provide meaningful clinical benefit to people with advanced cancers,” said Dr. Eric H. Rubin, senior vice president, early-stage development, clinical oncology, Merck Research Laboratories. “We are encouraged by these early findings with our STING agonist, most notably the observations of several robust anti-tumor responses in patients receiving MK-1454 in combination with KEYTRUDA. Further studies are ongoing.”

Study Design and Findings for MK-1454 (Abstract #LBA15)

In this Phase 1, open-label, multi-arm, multicenter, dose-escalation clinical trial (NCT03010176), MK-1454 was administered to patients with advanced solid tumors or lymphomas by intratumoral injection every week for nine weeks for three cycles then every three weeks thereafter. Dose escalations for MK-1454 were 10-3,000 µg (MK-1454 monotherapy arm) and 90-2,000 µg (MK-1454 in combination with KEYTRUDA arm) using accelerated titration followed by modified toxicity probability interval design. KEYTRUDA was administered as an intravenous (IV) injection at a dose of 200 mg every three weeks. Patients receiving MK-1454 as monotherapy who progressed while on therapy were eligible for crossover to the MK-1454-KEYTRUDA combination arm. Study objectives included evaluation of safety, tolerability, pharmacodynamics, pharmacokinetics and tumor responses evaluated using RECIST v1.1 criteria.

Interim data presented at ESMO were based on findings from 26 patients enrolled in the MK-1454 monotherapy arm and 25 patients enrolled in the combination arm with KEYTRUDA, plus 9 patients who crossed over from monotherapy to receive the combination regimen. In the monotherapy arm, no complete or partial responses were observed (n=0/20). In the combination arm, partial responses were observed in 24 percent of patients (n=6/25) (three head and neck squamous cell carcinoma, one triple-negative breast cancer, and two anaplastic thyroid carcinoma), with median reductions of 83 percent in the size of both target-injected and non-injected tumors. At the time of analysis, all of the partial responses were ongoing and had lasted six months or longer. None of the responders had previously received a PD-1/PD-L1 inhibitor therapy. The disease control rates were 20 percent and 48 percent for the monotherapy and combination arms, respectively.

Treatment-related adverse events (TRAEs) occurred in 82.6 percent (n=19/23) and 82.1 percent (n=23/28) of patients in monotherapy and combination arms, respectively. TRAEs resulting in trial discontinuation occurred in 7.1 percent of patients (n=2/28) in the combination arm. No TRAE discontinuations were recorded in patients in the monotherapy arm. The most common TRAEs (occurring in ≥10% of patients) in both study arms included: pyrexia, injection site pain, chills, and fatigue. In the monotherapy arm, additional TRAEs occurring in ≥10% of patients included: nausea, myalgia, headache, and tumor pain. In the combination arm, additional TRAEs occurring in ≥10% of patients included: pruritus, diarrhea, rash, and tachycardia.

About STING and MK-1454

STING is a signaling molecule that plays an important role in the body’s first line of defense against pathogens, such as bacteria and viruses (innate immune system). When activated, STING triggers the production of inflammatory proteins that can stimulate the immune system leading to the deployment of T cells, which are important in generating an effective immune mediated response to cancer cells.

Merck is exploring the role of the STING pathway across a variety of tumors as monotherapy and in combination with the company’s anti-PD-1 therapy, KEYTRUDA. MK-1454 is an investigational small molecule STING agonist administered as an intratumoral injection that is currently being evaluated in a Phase 1 clinical trial for the treatment of solid tumors and lymphomas (ClinicalTrials.gov, NCT03010176).

About KEYTRUDA (pembrolizumab) Injection 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 850 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin or cisplatin, as appropriate.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy.

In adults with PMBCL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with PMBCL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

  • solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
  • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Seite 1 von 5
Wertpapier
Merck & Co
Mehr zum Thema
USATwitterMerckESMHSC


0 Kommentare

Schreibe Deinen Kommentar

Bitte melden Sie sich an, um zu kommentieren. Anmelden | Registrieren

 

Disclaimer

Meistgelesene Nachrichten des Autors

Titel
Titel
Titel

Nachrichten zu den Werten

ZeitTitel
16.11.18
14.11.18
13.11.18
12.11.18
09.11.18
09.11.18
07.11.18
30.10.18
29.10.18
25.10.18