Phase 1/2 Study of EIK1005 Monotherapy and EIK1005 Plus Pembrolizumab in Patients With Advanced Solid Tumors

The primary objective is to evaluate the safety and tolerability of EIK1005 as monotherapy and in combination with pembrolizumab, with determination of the maximum tolerated dose or maximum administered dose in Part 1, and dose optimization in Part 2. This is clinically relevant for defining a tolerable dose range and supporting further development in advanced solid tumors. The secondary objectives are to assess preliminary antitumor activity of EIK1005 as monotherapy and in combination with pembrolizumab in Part 1, and to assess preliminary antitumor activity during dose optimization in Part 2. In addition, the plasma pharmacokinetic profile of EIK1005 is characterized as monotherapy and in combination with pembrolizumab across Parts 1 and 2.

The trial enrolled 111 participants with advanced solid tumors. The study population included adults of both sexes, with an age range of 18 years and older. Participants were selected on the basis of histologically or cytologically documented unresectable or metastatic disease, a life expectancy of at least 3 months, measurable disease at baseline, an ECOG performance status of 0 to 1, and adequate organ and marrow function. In Part 1A, prior progression after or intolerance to at least one standard treatment regimen in the advanced setting was required, with preference for participants who had progressed after immune checkpoint inhibitor therapy or after platinum-, alkylating-, or topoisomerase-containing chemotherapy. In Part 1B and Part 2, locally confirmed MSI-H or dMMR status was required, with archival tumor tissue for central confirmation. No information was provided regarding diet, physical activity, or other lifestyle characteristics.

This is a multicenter, multi-part, integrated phase 1/2 study of EIK1005 as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors. The trial is designed to evaluate safety and tolerability, determine the maximum tolerated dose or maximum administered dose in Part 1, and support dose optimization in Part 2. Treatment is administered orally for EIK1005 and by intravenous infusion for pembrolizumab. The overall study duration is estimated from 2026-06-01 to 2029-06-01. Study participation begins with a screening visit to assess eligibility, including age, life expectancy, tumor type, prior treatment history, measurable disease, performance status, and organ and marrow function. Participants then undergo study treatment and protocol-specified follow-up visits for ongoing safety assessment, adverse event monitoring, disease evaluation, and pharmacokinetic sampling. An end-of-study visit is performed at completion of participation to document final assessments. Expected participant involvement continues through treatment and follow-up until study completion or earlier discontinuation. Early termination may occur because of disease progression, unacceptable toxicity, intolerance, withdrawal of consent, investigator decision, or failure to meet protocol requirements.

The investigational treatment included EIK1005 sodium, administered as oral tablets in three strengths: 10 mg, 50 mg, and 200 mg. The pharmaceutical form was tablet, and the route of administration was oral. The study evaluated EIK1005 as monotherapy and in combination with pembrolizumab. The objective was to assess safety and tolerability and to determine the maximum tolerated dose or maximum administered dose in Part 1, and to evaluate safety and tolerability for dose optimization in Part 2. Dosing frequency and detailed administration schedule were not specified in the source data.

Pembrolizumab was used as a non-experimental treatment in the combination regimen. It was administered by intravenous infusion. The pharmaceutical form was listed as a parenteral formulation. No dose, dosing frequency, or infusion schedule was specified in the source data. Participant compliance monitoring procedures were not described in the source data.

Objective response will be assessed by the Investigator according to RECIST 1.1 and defined as the proportion of participants with a complete response or partial response. Disease control will also be assessed by RECIST 1.1 and defined as the proportion of participants with a best overall response of complete response, partial response, or stable disease. Duration of response will be assessed by RECIST 1.1 and defined as the time from the first documented evidence of complete response or partial response until disease progression or death due to any cause, whichever occurs first. Progression-free survival will be assessed by RECIST 1.1 and defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Pharmacokinetic parameters will be derived from plasma concentrations of EIK1005 following multiple doses and will include AUC0-24, AUCtau,ss, Cmax, t1/2, tmax, Rac-Cmax, and RacAUC.