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

Trial Title: A Study of Valemetostat Tosylate Plus Pembrolizumab Versus Pembrolizumab Alone in First-Line NSCLC Without Actionable Genomic Alterations

NCT ID: NCT06644768

Condition: Non-small Cell Lung Cancer
Lung Cancer

Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Pembrolizumab

Conditions: Keywords:
NSCLC
Tumor
pembrolizumab
valemetostat tosylate
DS-3201b
Immune checkpoint inhibitor
Programmed Cell Death 1 Ligand 1
MK-3475

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Sequential Assignment

Intervention model description: This is an open-label study.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: valemetostat tosylate
Description: Valemetostat will be administered orally once daily until RP2D of valemetostat is determined.
Arm group label: Phase 1b: Pembrolizumab + Valemetostat Tosylate
Arm group label: Phase 2: Pembrolizumab + Valemetostat Tosylate

Other name: DS-3201b

Other name: valemetostat

Intervention type: Drug
Intervention name: pembrolizumab
Description: One IV infusion Q3W on D1 of each 21-day cycle for a maximum of 35 cycles.
Arm group label: Phase 1b: Pembrolizumab + Valemetostat Tosylate
Arm group label: Phase 2: Pembrolizumab
Arm group label: Phase 2: Pembrolizumab + Valemetostat Tosylate

Other name: MK-3475

Summary: This study will compare Valemetostat Tosylate Plus Pembrolizumab vs Pembrolizumab Alone in First-line NSCLC Without Actionable Genomic Alterations

Detailed description: This trial will evaluate the safety and efficacy of valemetostat tosylate (DS-3201b) in combination with fixed-dose pembrolizumab versus pembrolizumab alone in participants with advanced or metastatic NSCLC without actionable genomic alterations, whose tumor has PD-L1 TPS ≥50%, and who have not received prior systemic therapy for advanced or metastatic NSCLC. The trial will be in 2 phases, dose escalation and dose expansion phases.

Criteria for eligibility:
Criteria:
Key Inclusion Criteria: 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: 1. Has no prior systemic therapy for advanced or metastatic disease. 2. 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. 3. 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. 4. 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 (minimum of 6 slides). 6. 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. 7. Has an ECOG PS of 0 or 1 at Screening. Key Exclusion Criteria 1. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting: 1. 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). 2. 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 (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. 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: 1. Mean QT interval corrected for heart rate using Fridericia's formula >470 ms (based on the average of screening triplicate 12-lead ECG determinations) 2. Myocardial infarction within 6 months prior to Screening 3. Uncontrolled angina pectoris within 6 months prior to Screening 4. New York Heart Association Class 3 or 4 congestive heart failure 5. 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: November 1, 2024

Completion date: April 30, 2030

Lead sponsor:
Agency: Daiichi Sankyo
Agency class: Industry

Collaborator:
Agency: Merck Sharp & Dohme LLC
Agency class: Industry

Source: Daiichi Sankyo

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06644768