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MK-3475

Phase 3

Carcinoma, Non-Small-Cell Lung | Small molecule | Oncology |Merck & Company, Inc.|Last Updated: Aug 28, 2026

Target and mechanism

Molecular targetPDCD1
Target classInhibitor
ModalitySmall molecule

Also known as Pembrolizumab, pembrolizumab, KEYTRUDA®, KEYTRUDA, Pembrolizumab Injection [Keytruda], Pembrolizumab (Keytruda), Pembrolizumab (MK-3475), Pembrolizumab Injection

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials9
Total Enrollment3,072

FDA Designations

PRIORITY_REVIEW

Clinical trial landscape

MK-3475 · 12 trials · 9 indications

Phase 3 4Phase 2 4Phase 1 4
NCT06623422A Study of Pembrolizumab (MK-3475) With or Without Intismeran Autogene (V940) in Participants With Non-small Cell Lung Cancer (V940-009/INTerpath-009)Carcinoma, Non-Small-Cell Lung
RECRUITING680 Analytics
NCT05298423Study of Pembrolizumab/Vibostolimab (MK-7684A) in Combination With Concurrent Chemoradiotherapy Followed by Pembrolizumab/Vibostolimab Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Stage III Non-small Cell Lung Cancer (MK-7684A-006)Carcinoma, Non-Small-Cell Lung
COMPLETED610 Analytics
NCT03302234Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)Carcinoma, Non-Small-Cell Lung
COMPLETED568 Analytics
NCT02864394Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)Carcinoma, Non-Small-Cell Lung
COMPLETED425 Analytics
PHASE3RECRUITING
A Study of Pembrolizumab (MK-3475) With or Without Intismeran Autogene (V940) in Participants With Non-small Cell Lung Cancer (V940-009/INTerpath-009)
Carcinoma, Non-Small-Cell LungUnlock trial analytics
PHASE3COMPLETED
Study of Pembrolizumab/Vibostolimab (MK-7684A) in Combination With Concurrent Chemoradiotherapy Followed by Pembrolizumab/Vibostolimab Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Stage III Non-small Cell Lung Cancer (MK-7684A-006)
Carcinoma, Non-Small-Cell LungUnlock trial analytics
PHASE3COMPLETED
Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)
Carcinoma, Non-Small-Cell LungUnlock trial analytics
PHASE3COMPLETED
Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)
Carcinoma, Non-Small-Cell LungUnlock trial analytics

Study Endpoints

Primary Endpoints

Disease-Free Survival (DFS)
Up to ~97 months

DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, as assessed by the investigator, or death due to any cause, whichever occurs first.

Number of Participants Who Experience at Least One Adverse Event (AE)
Up to approximately 48 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Up to approximately 48 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Overall Survival (OS)
Up to approximately 32 months (through data cut-off date: 01 Sep 2020)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. The median survival (in months) and the associated 95% confidence intervals (CIs) were reported using Kaplan-Meier method was used. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) was used to estimate hazard ratio (HR) and 95% CIs for first course study treatment per protocol.

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)
Up to approximately 32 months (through data cut-off date 01 Sep 2020)

PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in sum of diameters of target lesions. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The median survival (in months) and associated 95% CIs were reported using Kaplan-Meier method. Cox regression model with Efron's method of tie handling with treatment as covariate stratified by ECOG performance status (0 vs. 1), geographic region of the enrolling site (East Asia vs. non-East Asia), and predominant tumor history (squamous vs. non-squamous) was used to estimate HR and 95% CIs for first course study treatment per protocol.

Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors
Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With PD-L1 Positive (TPS ≥50%) Tumors
Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

Time to Death or Distant Metastasis
From start of treatment until death or distant metastasis (estimate 18 months) up to a maximum of 47 months.

Time to Death or Distant Metastasis is defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that was outside of the radiation field according to RECIST 1.1 or proven by biopsy. The Primary objective in the study was to determine if consolidation therapy with pembrolizumab following concurrent chemoradiation improves time to death or distant metastatic disease, depending on which occurs first, in subjects with inoperable or unresectable stage IIIA or IIIB NSCLC.

Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Up to approximately 53 months

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by investigator.

Locoregional Recurrence Rates in Cohorts 1 and 2
Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)

-The percentage of participants who developed local-regional recurrence within one year of surgery

Distant Failure Rate in Cohorts 1 and 2
Within 1 year of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)

-The percentage of participants who developed distant failure within one year of surgery. Distant disease is cancer that is found in another part of the body that is far away from where the original (primary) tumor first formed.

Rate of Major Pathologic Treatment Effect in Cohort 1
At the time of surgery (surgery occurred within 13-22 days after neoadjuvant MK-3475 dose)

* Major pathologic treatment effect=pathologic tumor response (pTR). * pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\>10%), pTR-1 (10-49%), and pTR-2 (≥50%).

Rate of Major Pathologic Treatment Effect in Cohort 2
At the time of surgery (surgery occurred within 13-22 days after last neoadjuvant MK-3475 dose)

* Major pathologic treatment effect=pathologic tumor response (pTR). * pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\>10%), pTR-1 (10-49%), and pTR-2 (≥50%).

Tumor Infiltrating T Lymphocyte (TIL) Density
2 weeks. TIL density is determined in surgical tumor tissue; on-study surgery occurs 14 days (+/- 5 days) after Neoadjuvant Day 1.

To measure changes in tumor infiltrating T lymphocyte (TIL) density, defined as % total cells. It will be assessed using pooled Group A and Group B patients.

Cell Cycle and Cancer Proliferation Genetic Signature
2 weeks. Cell cycle/cancer proliferation genetic signature is determined in surgical tumor tissue; on-study surgery occurs 14 days (+/- 5 days) after Neoadjuvant Day 1.

To measure changes in cell cycle and cancer proliferation genetic signature; these results are reported using Gene Set Variation Analysis (GSVA) absolute enrichment scores (ES). GSVA scores are unit-less scores derived by comparing mRNA expression of a specific gene set to genes outside of the gene set in a sample. In this case, GSVA scores for "Farmers\_breast\_cancer\_cluster\_2, as previously described" were utilized. PMID 30742122 (https://pubmed.ncbi.nlm.nih.gov/30742122/) and PMID 23323831 (https://pubmed.ncbi.nlm.nih.gov/23323831/) It will be assessed using pooled Group A and Group B patients.

Incidence of Treatment-Emergent Adverse Events
5 years. Although there is still 1 patient on active study treatment as of today (4/1/2024), we stopped looking at this information as of 6/2/2022 for study reporting purposes.

Number of Participants who Experienced a Serious Adverse Event (SAE) or Event of Clinical Interest (ECI) Deemed At Least Possibly Related to Pembrolizumab (MK3475). The following are measured as part of safety: laboratory safety assessments, KPS status, vital signs and physical examinations.

Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Up to approximately 24 months

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be reported.

Part B: Number of Participants Who Experience One or More Adverse Events (AEs)
Up to approximately 27 months

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be reported.

Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE)
Up to approximately 24 months

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study intervention due to an AE will be reported.

Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
Up to approximately 3 Weeks

A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.

Maximum Tolerated Dose (MTD) of MK-3475 When Combined With MLA - Phase I Only
Completion of Cycle 1 (each cycle is 3 weeks)

The MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experienced dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached, or failing that, 200 mg of MK-3475 every 3 weeks will be considered the MTD.

Progression-free Survival (PFS) - Phase II Only
Through completion of follow-up (median length of follow-up 338 days, full range 43-2468 days).

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

Dose Limiting Toxicities
126 Days (six 21-day cycles)

Patients are seen in clinic 12 times over 126 days to determine any changes in signs or symptoms that may represent drug toxicity. Drug toxicity is defined as events that required holding or delaying treatment.

Secondary Endpoints

Overall Survival (OS)
Up to ~129 months
Distant Metastasis-Free Survival (DMFS)
Up to ~129 months
Disease-Free Survival 2 (DFS2)
Up to ~129 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Pembrolizumab + Intismeran autogeneEXPERIMENTALFor neoadjuvant treatment, participants will receive pembrolizumab 200 mg via intravenous (IV) infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m\^2 or carboplatin area under the curve \[AUC\] 5 or 6 mg/mL/min, pemetrexed 500 mg/m\^2, gemcitabine 1000 mg/m\^2, paclitaxel 175 mg/m\^2 or 200 mg/m\^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to \~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS intismeran autogene 1 mg via intramuscular (IM) injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to \~42 weeks).
Pembrolizumab + PlaceboACTIVE_COMPARATORFor neoadjuvant treatment, participants will receive pembrolizumab 200 mg via IV infusion every 3-week cycle for up to 4 cycles PLUS background chemotherapy via IV infusion (cisplatin 75 mg/m\^2 or carboplatin AUC 5 or 6 mg/mL/min, pemetrexed 500 mg/m\^2, gemcitabine 1000 mg/m\^2, paclitaxel 175 mg/m\^2 or 200 mg/m\^2 given at a dose and combination per investigator's choice) every 3-week cycle for up to 4 cycles (total neoadjuvant treatment duration of up to \~12 weeks). After surgical resection, for adjuvant treatment, participants will receive pembrolizumab 400 mg via IV infusion every 6-week cycle for up to 7 cycles PLUS matching placebo via IM injection every 3 weeks for up to 9 doses (total adjuvant treatment duration of up to \~42 weeks).
pembrolizumab/vibostolimab coformulation+chemotherapy+radiotherapyEXPERIMENTALFor the first 3 cycles, participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) intravenously (IV) on Day 1 plus 3 cycles of investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy during Cycles 2, 3. Participants receive pembrolizumab/vibostolimab for Cycles 4-20 or until discontinuation (up to \~14 months). Cycles 1-20 are 21-day cycles. As of protocol amendment 4, participants receiving pembrolizumab/vibostolimab must stop ongoing treatment with pembrolizumab/vibostolimab and will be offered the option to transition to post-cCRT durvalumab consolidation therapy, to complete up to 1 year of consolidation immunotherapy.
chemotherapy+radiotherapy+durvalumabACTIVE_COMPARATORFor the first 3 cycles, participants will receive investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy during Cycles 2 and 3. Following concurrent chemoradiotherapy (cCRT), participants receive durvalumab 10 mg/kg every 2 weeks for up to an additional 26 cycles or until discontinuation (up to approximately 14 months). cCRT Cycles 1-3=21-day cycles; durvalumab Cycles 1-26=14-day cycles.
Pembrolizumab + IpilimumabEXPERIMENTALParticipants receive 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.
PembrolizumabEXPERIMENTALParticipants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).
DocetaxelEXPERIMENTALParticipants with NSCLC receive Docetaxel 75 mg/m\^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Experimental ArmEXPERIMENTALPembrolizumab -200 mg IV 3 weeks
Pembrolizumab + BoserolimabEXPERIMENTALOn Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).
Pembrolizumab + MK-4830EXPERIMENTALOn Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years).
Pembrolizumab + MK-0482EXPERIMENTALOn Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years).
Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475EXPERIMENTAL* MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. * Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: * risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) * optional image-guided radiation therapy * risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course * MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based surgical pathology from standard of care surgery. These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.
Cohort 2: Neoadjuvant MK-3475EXPERIMENTAL-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery)
Pre-surgery MK-3475EXPERIMENTAL-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK3475) pre-surgery at pre-determine dosage followed by Pembrolizumab at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously
No MK-3475 at Pre-SurgeryACTIVE_COMPARATOR-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK-3475) at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously
Part A: Pembrolizumab+Vibostolimab+Carboplatin + PaclitaxelEXPERIMENTALOn Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Part A: Pembrolizumab+Vibostolimab+Carboplatin + PemetrexedEXPERIMENTALOn Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Part A: Pembrolizumab+Boserolimab+Carboplatin+PaclitaxelEXPERIMENTALOn Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Part A: Pembrolizumab+Boserolimab+Carboplatin+PemetrexedEXPERIMENTALOn Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS pemetrexed 500 mg/m\^2 IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).
Part A: Pembrolizumab+MK-4830+Carboplatin+PaclitaxelEXPERIMENTALOn Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Part A: Pembrolizumab+MK-4830+Carboplatin+PemetrexedEXPERIMENTALOn Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Part A: Pembrolizumab+MK-0482+Carboplatin+PaclitaxelEXPERIMENTALOn Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Part A: Pembrolizumab+MK-0482+Carboplatin+PemetrexedEXPERIMENTALOn Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
Part B: Pembrolizumab + I-DXdEXPERIMENTALOn Day 1 of each 3-week cycle, participants with squamous and nonsquamous NSCLC will receive pembrolizumab 200 mg IV for up to 2 years, PLUS I-DXd in escalating doses until progressive disease or toxicity.
Part B: Pembrolizumab + Carboplatin + I-DXdEXPERIMENTALOn Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS I-DXd IV in escalating doses until PD or toxicity.
Part B: Pembrolizumab + Carboplatin + HER3-DXdEXPERIMENTALOn Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS HER3-DXd IV in escalating doses until PD or toxicity.
Phase I: MK-3475 + MLA Dose Level 1EXPERIMENTALMK-3475 will be given at 100 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity.
Phase I: MK-3475 + MLA Dose Level 2EXPERIMENTALMK-3475 will be given at 150 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity.
Phase I: MK-3475 + MLA Dose Level 3EXPERIMENTALMK-3475 will be given at 200 mg intravenously (IV) every 3 weeks starting no more than 1 week after MLA until progression or unacceptable toxicity.
Phase II: MK-3475 + MLAEXPERIMENTALMK-3475 will be given at 200 mg intravenously (IV) every 3 weeks no more than 1 week after MLA, or no more than 1 week after biopsy (if no surgical debulking). This dose was determined in the Phase I portion of the trial.
Phase II: MK-3475 OnlyEXPERIMENTALMK-3475 will be given at 200 mg intravenously (IV) every 3 weeks beginning 3 weeks after surgical debulking or no more than 1 week after biopsy (if no surgical debulking). This dose was determined in the Phase I portion of the trial.
MK-3475 + GemcitabineEXPERIMENTAL200mg MK-3475 200 given by IV infusion every 3 weeks, for 2 years, or until disease progression and Gemcitabine 1250 mg/m2 iv Days 1, 8 every 3 weeks, for maximum 6 cycles.

Interventions

NameTypeDescription
PembrolizumabBIOLOGICALIV Infusion
CisplatinDRUGIV infusion
CarboplatinDRUGIV infusion
PemetrexedDRUGIV infusion
GemcitabineDRUGIV infusion
PaclitaxelDRUGIV infusion
Intismeran autogeneBIOLOGICALIM injection
PlaceboOTHERIM injection
pembrolizumab/vibostolimabBIOLOGICALAdministered as an intravenous (IV) infusion
durvalumabBIOLOGICALAdministered as an IV infusion
etoposideDRUGEtoposide 50 mg/m\^2 is administered as an IV infusion on Days 1-5 of Cycles 1-2 and Days 8-12 of Cycle 3;
thoracic radiotherapyRADIATION60 Gray \[Gy\] in 2 Gy fractions for 30 days total administered as an external beam radiation
IpilimumabBIOLOGICALAdministered as an IV infusion every 6 weeks (Q6W)
DocetaxelDRUGDocetaxel administered IV at 75 mg/m\^2 on Day 1 of each 21-day cycle as per the approved product label.
BoserolimabBIOLOGICALIV infusion
MK-4830BIOLOGICALIV infusion
diphenhydramineDRUGPO
acetaminophenDRUGPO
MK-0482BIOLOGICALIV infusion
MK-3475 (neoadjuvant)BIOLOGICAL -
SurgeryPROCEDUREStandard of care
Intensity modulated radiation therapyRADIATIONRecommended, standard of care
Image-guided radiation therapyRADIATIONRecommended, standard of care
MK-3475 (adjuvant)BIOLOGICAL -
Peripheral bloodPROCEDURE-Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery
MK-3475DRUG -
VibostolimabBIOLOGICALIV infusion
Ifinatamab Deruxtecan (I-DXd)BIOLOGICALIV infusion
HER3-DXdBIOLOGICALIV Infusion
MRI-guided laser ablationDEVICEMLA is a minimally invasive laser surgery, which employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of the tumor mass where it delivers hyperthermic ablation from the core to the rim.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites241

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has histologically/cytologically confirmed diagnosis of previously untreated and pathologically confirmed resectable clinical Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC) \[American J...

Countries:United StatesArgentinaAustraliaBelgiumBrazilBulgariaCanadaChileColombiaFinlandFranceGermanyGreeceHungaryIrelandIsraelItalyJapanNetherlandsNew ZealandPeruPolandRomaniaSingaporeSouth KoreaSpainSwedenTaiwanThailandTurkey (Türkiye)United KingdomChinaCosta RicaCzechiaDominican RepublicGuatemalaMalaysiaMexicoPhilippinesPortugalSouth AfricaUkraineLatvia
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Recent Changes (Last 90 Days)

HIGHAug 28, 2026NCT05298423Status: ACTIVE_NOT_RECRUITING → COMPLETED
HIGHAug 28, 2026NCT05298423Status: ACTIVE_NOT_RECRUITING → COMPLETED
LOWAug 27, 2026NCT06623422lastUpdatePostDate: changed
LOWAug 27, 2026NCT06623422lastUpdatePostDate: changed
LOWAug 25, 2026NCT04165070lastUpdatePostDate: changed
LOWAug 25, 2026NCT04165070lastUpdatePostDate: changed
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MEDIUMJul 28, 2026NCT04165070Completion: 2032-02-13 → 2032-10-13
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Frequently asked questions about MK-3475

What is MK-3475 used for?

MK-3475, also known as pembrolizumab and marketed as KEYTRUDA, is an investigational antibody being studied for several oncology indications, including Primary Mediastinal Large B-cell Lymphoma (PMBCL), prostate cancer, anal cancer, squamous cell carcinoma, non-small-cell lung cancer, B-cell lymphoma, and oligometastatic squamous cell carcinoma of the head and neck.

What does MK-3475 target?

MK-3475 is a monoclonal antibody (target class -mab) that targets the PD-1 receptor. By binding to PD-1, it is designed to block the interaction with its ligands, potentially enhancing the immune system's ability to fight cancer cells.

Who makes MK-3475?

MK-3475 is developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is conducting clinical trials to evaluate the drug's safety and efficacy across multiple cancer types.

What phase is MK-3475 in?

MK-3475 is in Phase 1 clinical development. It has received a Priority Review designation from the FDA. The drug is investigational and not yet approved, with ongoing trials assessing its use in various cancers.

What clinical trials is MK-3475 in?

MK-3475 is being studied in 17 clinical trials, with 5 active and 12 completed, enrolling over 8,000 participants. Notable trials include NCT02635360 for cervical cancer, NCT04875195 for Hodgkin's lymphoma and PMBCL, NCT04976634 for solid tumors, and NCT05815927 for head and neck cancer.

Is MK-3475 the same as pembrolizumab?

Yes, MK-3475 is the same as pembrolizumab, which is also known by the brand name KEYTRUDA. The drug is referred to by multiple names including Pembrolizumab 200 mg, Pembrolizumab Injection, and Pembrolizumab (MK-3475), among others.