Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06623422 | A Study of Pembrolizumab (MK-3475) With or Without Intismeran Autogene (V940) in Participants With Non-small Cell Lung Cancer (V940-009/INTerpath-009) | PHASE3 | RECRUITING | 680 | — | — | Oct 21, 2024 | Jan 26, 2038 | May 15, 2026 | 232 | United States, Argentina +29 |
| NCT05298423 | 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) | PHASE3 | ACTIVE NOT_RECRUITING | 611 | — | — | May 3, 2022 | Aug 19, 2026 | Aug 1, 2025 | 160 | United States, Argentina +23 |
| NCT03302234 | Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598) | PHASE3 | COMPLETED | 568 | — | — | Dec 14, 2017 | Sep 7, 2022 | Sep 26, 2023 | 187 | United States, Argentina +22 |
| NCT02864394 | Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033) | PHASE3 | COMPLETED | 425 | — | — | Sep 7, 2016 | Oct 14, 2022 | Sep 19, 2024 | - | — |
| NCT02343952 | Consolidation Pembrolizumab Following Chemoradiation in Patients With Inoperable/Unresectable Stage III NSCLC | PHASE2 | COMPLETED | 93 | — | — | Mar 9, 2015 | Jan 1, 2021 | Sep 13, 2023 | 15 | United States |
| NCT04165096 | KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C/KEYMAKER-U01C) | PHASE2 | COMPLETED | 128 | — | — | Jan 21, 2020 | May 28, 2025 | May 13, 2026 | 39 | United States, Hungary +5 |
| NCT04165083 | KEYMAKER-U01 Substudy 2: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Treatment-naïve Participants With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Positive Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01B/KEYMAKER-U01B) | PHASE2 | COMPLETED | 102 | — | — | Dec 19, 2019 | Oct 31, 2025 | Nov 26, 2025 | 39 | United States, Hungary +5 |
| NCT04165070 | KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) | PHASE1 | RECRUITING | 450 | — | — | Dec 19, 2019 | Feb 13, 2032 | May 18, 2026 | 46 | United States, Hungary +7 |
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.
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.
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.
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.
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.
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 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).
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 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 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.
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.
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.
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Pembrolizumab + Intismeran autogene | EXPERIMENTAL | For 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 + Placebo | ACTIVE_COMPARATOR | For 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+radiotherapy | EXPERIMENTAL | For 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+durvalumab | ACTIVE_COMPARATOR | For 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 + Ipilimumab | EXPERIMENTAL | Participants 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. |
| Pembrolizumab | EXPERIMENTAL | Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months). |
| Docetaxel | EXPERIMENTAL | Participants 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 Arm | EXPERIMENTAL | Pembrolizumab -200 mg IV 3 weeks |
| Pembrolizumab + Boserolimab | EXPERIMENTAL | On 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-4830 | EXPERIMENTAL | On 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-0482 | EXPERIMENTAL | On 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). |
| Part A: Pembrolizumab+Vibostolimab+Carboplatin + Paclitaxel | EXPERIMENTAL | On 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 + Pemetrexed | EXPERIMENTAL | On 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+Paclitaxel | EXPERIMENTAL | On 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+Pemetrexed | EXPERIMENTAL | On 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+Paclitaxel | EXPERIMENTAL | On 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+Pemetrexed | EXPERIMENTAL | On 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+Paclitaxel | EXPERIMENTAL | On 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+Pemetrexed | EXPERIMENTAL | On 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-DXd | EXPERIMENTAL | On 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-DXd | EXPERIMENTAL | On 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-DXd | EXPERIMENTAL | On 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. |
| Name | Type | Description |
|---|---|---|
| Pembrolizumab | BIOLOGICAL | IV Infusion |
| Cisplatin | DRUG | IV infusion |
| Carboplatin | DRUG | IV infusion |
| Pemetrexed | DRUG | IV infusion |
| Gemcitabine | DRUG | IV infusion |
| Paclitaxel | DRUG | IV infusion |
| Intismeran autogene | BIOLOGICAL | IM injection |
| Placebo | OTHER | IM injection |
| pembrolizumab/vibostolimab | BIOLOGICAL | Administered as an intravenous (IV) infusion |
| durvalumab | BIOLOGICAL | Administered as an IV infusion |
| etoposide | DRUG | Etoposide 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 radiotherapy | RADIATION | 60 Gray \[Gy\] in 2 Gy fractions for 30 days total administered as an external beam radiation |
| Ipilimumab | BIOLOGICAL | Administered as an IV infusion every 6 weeks (Q6W) |
| Docetaxel | DRUG | Docetaxel administered IV at 75 mg/m\^2 on Day 1 of each 21-day cycle as per the approved product label. |
| Boserolimab | BIOLOGICAL | IV infusion |
| MK-4830 | BIOLOGICAL | IV infusion |
| diphenhydramine | DRUG | PO |
| acetaminophen | DRUG | PO |
| MK-0482 | BIOLOGICAL | IV infusion |
| Vibostolimab | BIOLOGICAL | IV infusion |
| Ifinatamab Deruxtecan (I-DXd) | BIOLOGICAL | IV infusion |
| HER3-DXd | BIOLOGICAL | IV Infusion |
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...