A Study of Valemetostat Tosylate Plus Pembrolizumab versus Pembrolizumab Alone in First-Line NSCLC Without Actionable Genomic Alterations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 29 Jan 2026

Decision date (initial)

2025-09-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc (Sponsor) and Merck Sharp & Dohme LLC (Collaborator)

External identifiers

EU CT number

2024-519671-26-00

ClinicalTrials.gov

NCT06644768

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Dose response, Efficacy, Others

Phase 1b only: To evaluate the safety and tolerability of valemetostat in combination with pembrolizumab and to determine the RP2D
Phase 2 only: To evaluate the efficacy of valemetostat in combination with pembrolizumab compared with pembrolizumab alone

Secondary objectives 4

1. Phase 2 only: To further evaluate the efficacy of valemetostat in combination with pembrolizumab compared with pembrolizumab alone
2. Phase 2 only: To assess the safety and tolerability of valemetostat in combination with pembrolizumab compared with pembrolizumab alone
3. Both phase 1 and phase 2: To evaluate the PK of valemetostat when administered in combination with pembrolizumab
4. Both phase 1 and phase 2: To assess the immunogenicity of pembrolizumab in combination with valemetostat

Conditions and MedDRA coding

Advanced or Metastatic Non-Small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Has signed and dated the ICF, prior to the start of any trial-specific qualification procedures.
2. Is an adult ≥18 years of age or the minimum legal age (whichever is greater) at the time of informed consent. (Follow local regulatory requirements if the legal age of adult voluntary consent for trial participation is >18 years old).
3. Has histologically documented NSCLC that meets all of the following criteria: a. Has no prior systemic therapy for advanced or metastatic disease. b. Has Stage IIIB or IIIC disease and is not a candidate for surgical resection or definitive chemoradiation, or Stage IV NSCLC disease at the time of enrollment/randomization (based on the American Joint Committee on Cancer, Eighth Edition). Participants with early-stage NSCLC who have relapsed should be restaged during Screening to ensure their eligibility for the trial. c. Has documented negative test results for EGFR, ALK, and ROS1 actionable genomic alterations based on analysis of tumor tissue. If test results for EGFR, ALK, and ROS1 are not available, participants are required to undergo testing with approved and/or validated tests per local regulations for these genomic alterations. Participants with squamous NSCLC are only required to undergo EGFR, ALK, and ROS1 testing if they have no history of tobacco smoking or were diagnosed with NSCLC at <40 years of age. d. Has no known actionable genomic alterations in NTRK, BRAF, RET, MET, or other actionable oncogenic drivers with locally approved therapies (testing for genomic alterations besides EGFR, ALK, and ROS1 is not required prior to enrollment/randomization). Participants whose tumors harbor KRAS mutations are eligible for the trial.
4. Has measurable disease on CT or MRI based on local imaging assessment using RECIST v1.1
5. Has a tumor expressing PD-L1 TPS ≥50% as determined by local testing using 22C3 pharmDx PD-L1 IHC assay. In regions where PD-L1 (TPS ≥50%) testing by 22C3 pharmDx is not considered SOC, PD-L1 expression levels will be determined by central testing.
6. Has provided an archival formalin-fixed tumor tissue sample for the assessment of biomarkers. If archival tissue is not available, a new pretreatment biopsy is required, if clinically feasible.
7. Has an ECOG PS of 0 or 1 at Screening.

Exclusion criteria 10

1. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting: a. Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, or CD137). b. Has previously been treated with any enhancer of zeste homolog inhibitors.
2. Participants who received adjuvant or neoadjuvant therapy other than those listed in the exclusion criterion above are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the current diagnosis of advanced or metastatic disease.
3. Has received a live vaccine or live attenuated vaccine within 30 days prior to the first dose of trial intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccines. Note: Administration of killed vaccines is allowed.
4. Has an active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years, except for replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid). Inhaled, intranasal, intraocular, intra-articular, or topical steroids and adrenal replacement steroids are permitted in the absence of active autoimmune disease.
5. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (at doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial intervention. Note: Short-course systemic corticosteroids (eg, prevention of/treatment for transfusion reaction) or steroid use for a noncancer indication (eg, adrenal replacement) is permissible.
6. Has a known active or untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate, provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks by repeat imaging (note: repeat imaging should be performed during trial screening), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of trial intervention. Note: A CT scan or MRI scan of the brain at Baseline is required for all participants. For participants in whom CNS metastases are first discovered at Screening, the treating investigator should delay trial intervention to complete any necessary treatment followed by a proper washout period and document the stability of CNS metastases with repeat imaging at least 4 weeks later (in which case repetition of all screening activities may be required).
7. Has uncontrolled or significant cardiovascular disease, including the following: a. Mean QT interval corrected for heart rate using Fridericia's formula >470 ms (based on the average of screening triplicate 12-lead ECG determinations) b. Myocardial infarction within 6 months prior to Screening c. Uncontrolled angina pectoris within 6 months prior to Screening d. New York Heart Association Class 3 or 4 congestive heart failure e. Uncontrolled hypertension (resting systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg)
8. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
9. Has a history of radiation pneumonitis.
10. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1b only: Number of Participants with Dose-Limiting Toxicities, Treatment-Emergent Adverse Events, and other safety parameters during the trial.
2. Phase 2 only: Progression-Free survival by blinded independent central review (BICR).

Secondary endpoints 5

1. Phase 2 only: Objective Response Rate (ORR) by BICR
2. Phase 2 only: Duration of Response (DoR) by BICR
3. Phase 2 only: Disease Control Rate (DCR) by BICR
4. Phase 2 only: Overall Survival (OS)
5. Phase 2 only: Progression-Free Survival by Investigator

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 7

Locations

3 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications