A Study of Valemetostat Tosylate Plus Pembrolizumab Versus Pembrolizumab Alone in First-Line NSCLC Without Actionable Genomic Alterations
A Multicenter, Randomized, Open-Label, Phase 1b/2 Trial Of Valemetostat Tosylate Plus Pembrolizumab Vs Pembrolizumab Alone in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Whose Tumors Express PD-L1 With Tumor Proportion Score ≥50% Without Actionable Genomic Alterations
3 other identifiers
interventional
137
6 countries
45
Brief Summary
This study will compare Valemetostat Tosylate Plus Pembrolizumab vs Pembrolizumab Alone in First-line NSCLC Without Actionable Genomic Alterations
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 nonsmall-cell-lung-cancer
Started Oct 2024
Longer than P75 for phase_1 nonsmall-cell-lung-cancer
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 1, 2024
CompletedFirst Posted
Study publicly available on registry
October 16, 2024
CompletedStudy Start
First participant enrolled
October 30, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2030
October 9, 2025
October 1, 2025
3.4 years
October 1, 2024
October 7, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase 1b: Number of Participants with Dose-Limiting Toxicities
Total number of participants with A Dose-Limiting Toxicity (DLT) at each dose level of valemetostat in combination with pembrolizumab per National Cancer Institute - Common Terminology Criteria for Adverse Events version 5.0.
From day of first dose on Day 1 to Day 21 in Cycle 1 (21 days), or before the administration of Cycle 2, up to 24 days
Phase 1b: Number of Participants with Treatment-Emergent Adverse Events
Incidence of TEAEs, Grade 3 or 4 TEAEs, deaths, TESAEs, TEAEs leading to dose modifications (including interruption, reduction, and discontinuation), and AESIs using the National Cancer Institute - Common Terminology Criteria for Adverse Events version 5.0
From date of first dose to 30 days after last dose, up to approximately 31 months
Phase 2: Progression-Free Survival by BICR
PFS is the time from the date of randomization to the date of radiographic disease progression as assessed by blinded independent central review (BICR) per RECIST v1.1 or death from any cause, whichever occurs first.
From date of randomization to the date of radiographic disease progression, or death from any cause, whichever occurs first, up to approximately 31 months
Secondary Outcomes (5)
Phase 2: Objective Response Rate
From date of randomization to the date of radiographic disease progression, or death from any cause, whichever occurs first, up to approximately 31 months
Phase 2: Duration of Response
From date of randomization to the date of radiographic disease progression, or death from any cause, whichever occurs first, up to approximately 31 months
Phase 2: Disease Control Rate
From date of randomization up to approximately 31 months
Phase 2: Overall Survival
From date of randomization the date of death from any cause, up to approximately 31 months
Phase 2: Progression-Free Survival by Investigator
From date of randomization to the date of radiographic disease progression, or death from any cause, whichever occurs first, up to approximately 31 months
Study Arms (3)
Phase 1b: Pembrolizumab + Valemetostat Tosylate
EXPERIMENTALParticipants will be provided with pembrolizumab at standard dose of 200 mg intravenously (IV) Q3W, and valemetostat will be provided per a dose escalation schedule, with an initial starting dose of 150 mg by mouth once daily.
Phase 2: Pembrolizumab + Valemetostat Tosylate
EXPERIMENTALParticipants will be provided with pembrolizumab at standard dose of 200 mg IV Q3W, and valemetostat will be provided per recommended phase 2 dose (RP2D)
Phase 2: Pembrolizumab
ACTIVE COMPARATORParticipants will be provided with pembrolizumab at standard dose of 200 mg IV Q3W
Interventions
Valemetostat will be administered orally once daily until RP2D of valemetostat is determined.
One IV infusion Q3W on D1 of each 21-day cycle for a maximum of 35 cycles.
Eligibility Criteria
You may qualify if:
- Has signed and dated the ICF, prior to the start of any trial-specific qualification procedures.
- 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).
- Has histologically documented NSCLC that meets all of the following criteria:
- Has no prior systemic therapy for advanced or metastatic disease.
- 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.
- 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 performed locally 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.
- 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.
- Has measurable disease on CT or MRI based on local imaging assessment using RECIST v1.1
- 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 (minimum of 6 slides).
- Has provided a formalin-fixed tumor tissue sample for the assessment of biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected.
- Has an ECOG PS of 0 or 1 at Screening.
You may not qualify if:
- Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:
- 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).
- Has previously been treated with any enhancer of zeste homolog inhibitors.
- 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.
- Has an active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of systemic disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Inhaled, intranasal, intraocular, intra-articular, or topical steroids and adrenal replacement steroids are permitted in the absence of active autoimmune disease.
- 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.
- 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).
- Has uncontrolled or significant cardiovascular disease, including the following:
- Mean QT interval corrected for heart rate using Fridericia's formula \>470 ms (based on the average of screening triplicate 12-lead ECG determinations)
- Myocardial infarction within 6 months prior to Screening
- Uncontrolled angina pectoris within 6 months prior to Screening
- New York Heart Association Class 3 or 4 congestive heart failure
- Uncontrolled hypertension (resting systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg)
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Daiichi Sankyolead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (45)
University of California San Diego (Ucsd)-Moores Cancer Center
La Jolla, California, 92037, United States
California Research Institute
Los Angeles, California, 90027, United States
Valkyrie Clinical Trials
Los Angeles, California, 90067, United States
Mayo Clinic Hospital
Jacksonville, Florida, 32224, United States
BRCR Global
Plantation, Florida, 33322-5426, United States
University of Kentucky Medical Center
Lexington, Kentucky, 40536, United States
Pikeville Medical Center
Pikeville, Kentucky, 41501, United States
Mayo Clinic - Rochester
Rochester, Minnesota, 55904, United States
Columbia University Irving Medical Center
New York, New York, 10032, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107, United States
Virginia Cancer Specialist
Fairfax, Virginia, 22031, United States
Hospital Italiano de Buenos Aires
Buenos Aires, 1199, Argentina
Instituto Alexander Fleming
Buenos Aires, 1426, Argentina
Sanatorio Allende
Córdoba, X5000JHQ, Argentina
Fundacion Ars Medica
N Salvador de Jujuy, 4600, Argentina
Centro de Investigacion Pergamino Sa
Pergamino, B2700CPM, Argentina
Instituto Medico de La Fundacion Estudios Clinicos
Rosario, 2000, Argentina
Clinica Viedma S.A.
Viedma, R8500ACE, Argentina
Centro de Pesquisas Clinica Reichow
Blumenau, 89010-340, Brazil
Clínica de Neoplasias Litoral Ltda.
ItajaĂ-, 88301-220, Brazil
CINPAM Centro Integrado De Pesquisa Da Amazonia
Manaus, 69005-080, Brazil
Liga Norte-Rio-Grandense Contra o Câncer
Natal, 59062-000, Brazil
Hospital Nossa Senhora da Conceicao
Porto Alegre, 91350-280, Brazil
Cepho - Centro de Estudos E Pesquisas de Hematologia E Oncologia
Santo André, 09060-650, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
Sao Jose Rio Preto, 15090-000, Brazil
Jilin Cancer Hospital
Changchun, 130000, China
The First Hospital of Jilin University
Changchun, 130021, China
Chengdu Shang Jin Nan Fu Hospital
Chengdu, 611730, China
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
Hangzhou, 242332, China
Harbin Medical University Cancer Hospital
Harbin, 150081, China
Jiamusi Cancer Hospital
Jiamusi, 154007, China
Shanghai East Hospital
Shanghai, 200120, China
The First Hospital of China Medical University
Shenyang, 110001, China
Tianjin Medical University Cancer Institute & Hospital
Tiyuan, 300060, China
Henan Cancer Hospital
Zhengzhou, 450003, China
Kyushu University Hospital
Fukuoka, 812-8582, Japan
National Cancer Center Hospital East
Kashiwa, 277-8577, Japan
Cancer Institute Hospital of JFCR
Kōtoku, 135-8550, Japan
NHO Nagoya Medical Center
Nagoya, 460-0001, Japan
Kitasato University Hospital
Sagamihara-shi, 252-0375, Japan
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Seoul National University Hospital
Seoul, 110-744, South Korea
The Catholic University of Korea, St. Vincent'S Hospital
Suwon, 16247, South Korea
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 1, 2024
First Posted
October 16, 2024
Study Start
October 30, 2024
Primary Completion (Estimated)
March 30, 2028
Study Completion (Estimated)
April 30, 2030
Last Updated
October 9, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
- Access Criteria
- Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/