Novel TLR Coagonist Combo Shows Responses in Stage IV NSCLC

EIK1001 is an intravenous (IV) small molecule, TLR 7/8 receptor dual agonist that is designed to target plasmacytoid and myeloid dendritic cells. Study authors theorized that providing a complementary mechanism to checkpoint inhibition with EIK1001 could improve expected outcomes in patients with NSCLC.

Encouraging clinical activity was reported in patients with stage IV non–small cell lung cancer (NSCLC) who received ELK1001, an investigational toll-like receptor (TLR) 7/8 coagonist, plus pembrolizumab (Keytruda), according to a presentation on findings from the phase 2 TeLuRide-005 trial (NCT06246110) at the European Society for Medical Oncology (ESMO) Congress 2025.1

The results indicated that the objective response rate (ORR) was 64% (95% CI, 41%-75%) among 50 evaluable patients. Additionally, the ORRs were 59% (95% CI, 41%-75%) and 75% (95% CI, 48%-93%) in patients with nonsquamous (n = 34) and squamous (n = 16) histology, respectively.

“In participants with advanced NSCLC, the addition of the TLR receptor 7/8 dual agonist EIK1001 to first-line, histology-specific standard-of-care [SOC] chemotherapy plus pembrolizumab demonstrates no dose-limiting toxicities [DLTs] observed during the initial safety run-in at 0.45 mg/m2, no additional safety concerns at the expanded dose of 0.60 mg/m2 when compared with SOC treatment, and preliminary clinical activity with an encouraging ORR and tumor shrinkage in all groups, in particular for participants with squamous histology and those with PD-L1 tumor proportion score [TPS] of at least 50%,” Richard J. Gralla, MD, FACP, FRCP Edin, senior study author, said in a presentation of the data.

Gralla is a professor in the Departments of Oncology (Medical Oncology) and Medicine (Oncology & Hematology), director of Oncology Research for the North Bronx Healthcare Network at Albert Einstein College of Medicine in New York, and the 2020 Giants of Cancer Care® awardee in the Supportive, Palliative, and/or Geriatric Care category.

What is EIK1001, and How Might it Help My Patients With Advanced NSCLC?

EIK1001 is an intravenous (IV) small molecule, TLR 7/8 receptor dual agonist that is designed to target plasmacytoid and myeloid dendritic cells. The agent was well tolerated per data from earlier phase 1 trials and showed evidence of activity even in heavily pretreated patients.

Study authors theorized that providing a complementary mechanism to checkpoint inhibition with EIK1001 could improve expected outcomes in patients with NSCLC.

What Was the Design of the Trial and What Were the Baseline Patient Characteristics?

Eligible patients included those with untreated stage IV nonsquamous or squamous NSCLC with no actionable driver mutations in the first-line setting, with an ECOG performance status of 0 or 1, and no symptomatic brain metastases.2 EIK1001 was administered at an IV weekly dose of 0.45 mg/m2 for 8 cycles, followed by every-3-week administration in combination with 200 mg of pembrolizumab for up to 35 cycles, plus histology-appropriate chemotherapy.1 Patients were then evaluated for DLTs during cycle 1, and 6 patients were included per histologic cohort. The cohort was then expanded to evaluate 0.6 mg/m2 of EIK1001 plus pembrolizumab and chemotherapy, with up to 25 patients per cohort.

Patients with nonsquamous histology received 500 mg/m2 of pemetrexed plus carboplatin at an area under the curve (AUC) 5 every 3 weeks for 4 cycles, plus optional pemetrexed maintenance. Patients with squamous histology received 200 mg/m2 of paclitaxel plus carboplatin at AUC 6 every 3 weeks for 4 cycles.

The primary end points in the safety run-in phase were DLTs and adverse effects (AEs), and AEs and the number of patients discontinuing treatment because of an AE in the expansion phase. Secondary end points were ORR and duration of response.

Baseline characteristics revealed that the mean and median ages were 67 (standard deviation, 10) and 68 (range, 23-83) years, respectively. Most patients were male (75%), prior smokers (64%), and had nonsquamous histology (66%). PD-L1 TPS was at least 50% in 36% of patients, between 1% and 49% in 41%, less than 1% in 22%, and missing in 1% of cases.

During the safety run-in, 6 patients with nonsquamous and 7 with squamous histology were enrolled. In dose expansion, 33 patients with nonsquamous and 13 with squamous histology were enrolled. “The frequency of AEs was similar across both the run-in and expansion phases and across both histologies,” Gralla said.

What Was the Efficacy of the Regimen According to PD-L1 TPS?

Among patients with PD-L1 TPS below 1% (n = 11), between 1% and 49% (n = 21), and 50% or greater (n = 17), the ORRs were 55% (95% CI, 23%-83%), 62% (95% CI, 38%-82%), and 71% (95% CI, 44%-90%), respectively. Of note, the PD-L1 expression level was missing for one patient who achieved a partial response.

What Events Defined the Safety Profile of the Regimen?

AEs that occurred in at least 20% of patients (n = 59) included fatigue (61.0%), nausea (45.8%), neutropenia (42.4%), anemia (40.7%), constipation (33.9%), diarrhea (32.2%), dizziness (30.5%), thrombocytopenia (29.1%), dyspnea (25.4%), decreased appetite (23.7%), headache (23.7%), hypotension (23.7%), pyrexia (23.7%), vomiting (22.0%), weight decrease (22.0%), and hypokalemia (20.3%). The safety events were largely related to the chemoimmunotherapy regimen, Gralla said.

Treatment-emergent AEs occurred in 94.9% of patients. Grade 3 AEs occurred in 71.2% of patients, and serious AEs occurred in 42.4%. A total of 6.8% of patients had AEs that led to death, but none were treatment related; 3.4% of AEs led to discontinuation. Cytokine release syndrome occurred in 11.9% of patients (grade 1, 8.5%; grade 2, 3.4%).

What Are the Next Steps for the Regimen in This Patient Population?

“Overall observed tolerability and preliminary clinical activity in the TeLuRide-005 study support further development of this novel treatment regimen for participants with advanced NSCLC,” Gralla concluded.

Disclosures: Gralla disclosed research support from the NIH/NCI R01 CA157409, Merck, and Eikon; participation in advisory boards for Eli Lilly and AstraZeneca; and no stock ownership.

References

1. Costin D, Meshad M, Jotte R, et al. TeLuRide-005: phase 2 study of EIK1001, a toll-like receptor 7/8 co-agonist with pembrolizumab + chemotherapy as first-line therapy in stage 4 non-small cell lung cancer. Presented at: 2025 ESMO Congress; October 17-25, 2025; Berlin, Germany. Abstract 1850MO.
2. A phase 2 study of EIK1001 in combo with pembrolizumab and chemotherapy in patients with stage 4 NSCLC. ClinicalTrials.gov. Updated April 10, 2025. Accessed October 20, 2025. https://clinicaltrials.gov/study/NCT06246110