Clinical Trials List
Protocol NumberMK3475-495
NCT Number(ClinicalTrials.gov Identfier)NCT03516981
Completed
2018-11-16 - 2023-09-30
Phase II
Recruiting5
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase 2 Precision Oncology Study of Biomarker-Directed, Pembrolizumab-(MK-3475, SCH 900475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (KEYNOTE-495; KeyImPaCT)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Wu-Chou Su Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- 楊朝能 Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
- Chao-Hua Chiu Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Recruiting
Audit
None
Co-Principal Investigator
- 林孟志 Division of Thoracic Medicine
- Chia-Cheng Tseng Division of Thoracic Medicine
- 林理涵 Division of Radiology
- Shau-Hsuan Li Division of Hematology & Oncology
- 李易濰 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林育麟 未分科
- Chong-Jen Yu Division of Thoracic Medicine
- 林家齊、林育麟、李日翔、林宗哲、廖斌志、徐偉勛 Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Shau-Hsuan Li Division of Hematology & Oncology
- 蕭慈慧 Division of Thoracic Medicine
- 林孟志 Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
- 李易濰 Division of Radiology
- 趙恒勝 Division of Thoracic Medicine
- Chia-Cheng Tseng Division of Thoracic Medicine
- 楊朝能 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced Non-Small Cell Lung Cancer
Objectives
Objective: To evaluate the clinical activity (as assessed by objective response rate [ORR]) of specific pembrolizumab-basedcombinations.
Test Drug
MK-3475
Active Ingredient
Pembrolizumab (Humanized anti-PD-1 mAb)
Dosage Form
Injection
Dosage
100 mg/ 4 mL/ vial
Endpoints
Primary Outcome Measures :
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) [ Time Frame: Up to ~2 years ]
ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by local site.
Secondary Outcome Measures :
Progression Free Survival (PFS) per RECIST 1.1 [ Time Frame: Up to ~2 years ]
PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by local site.
Overall Survival (OS) [ Time Frame: Up to ~2 years ]
OS is defined as the time from randomization to death due to any cause.
Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to ~2 years ]
An AE is any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of participants in each treatment arm experiencing an AE will be reported.
Number of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to ~2 years ]
An AE is any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of participants in each treatment arm that discontinued study drug due to an AE will be reported.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) [ Time Frame: Up to ~2 years ]
ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by local site.
Secondary Outcome Measures :
Progression Free Survival (PFS) per RECIST 1.1 [ Time Frame: Up to ~2 years ]
PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by local site.
Overall Survival (OS) [ Time Frame: Up to ~2 years ]
OS is defined as the time from randomization to death due to any cause.
Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to ~2 years ]
An AE is any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of participants in each treatment arm experiencing an AE will be reported.
Number of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to ~2 years ]
An AE is any untoward medical occurrence in participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of participants in each treatment arm that discontinued study drug due to an AE will be reported.
Inclution Criteria
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following
criteria apply:
1. Have a histologically or cytologically confirmed diagnosis of Stage IV
(American Joint Committee on Cancer [AJCC] v. 8) NSCLC and study
participants should not have had prior systemic therapy for advanced
disease.
2. Have confirmation that epidermal growth factor receptor– (EGFR-),
anaplastic lymphoma kinase– (ALK-), c-ros oncogene 1 (ROS1), or B
isoform of rapidly accelerated fibrosarcoma (B-Raf) directed therapy is not
indicated as primary therapy (documentation of absence of tumor activating
EGFR or B-Raf mutations AND absence of ALK or ROS1 gene
rearrangements). If participant’s tumor is known to have a predominantly
squamous histology, molecular testing for EGFR mutation and ALK and
ROS1 translocations will not be required, as this is not part of current
diagnostic guidelines.
3. Have measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology. Lesions situated in a previously irradiated area are
considered measurable if progression has been demonstrated in such
lesions.
4. Male/female subjects who are at least 18 years of age on the day of signing
the informed consent.
5. A male participant must agree to use a contraceptive as detailed in Protocol
Appendix 5 of this protocol during the treatment period and for at least 120
days after the last dose of study treatment and refrain from donating sperm
during this period.
6. A female participant is eligible to participate if she is not pregnant (see
Protocol Appendix 5), not breastfeeding, and at least one of the following
conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in Protocol
Appendix 5
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in Protocol
Appendix 5 during the treatment period and for at least 120 days after the
last dose of study treatment.
7. The participant (or legally acceptable representative if applicable) provides
written informed consent for the study. The participant may also provide
consent for Future Biomedical Research. However, the participant may
participate in the main study without participating in Future Biomedical
Research.
8. Have provided archival tumor tissue sample or newly obtained core or
excisional biopsy of a tumor lesion not previously irradiated. Newly
obtained biopsies are preferred to archival tissue. Repeat samples may be
required if adequate tissue is not provided.
9. Participants must have adequately controlled blood pressure (BP) with or
without antihypertensive medications, defined as BP ≤150/90 mm Hg at
Screening and no change in antihypertensive medications within 1 week
before Cycle 1/Day 1.
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 to 1.
11. Have adequate organ function. Specimens must be collected within 10 days
prior to the start of study treatment.
Participants are eligible to be included in the study only if all of the following
criteria apply:
1. Have a histologically or cytologically confirmed diagnosis of Stage IV
(American Joint Committee on Cancer [AJCC] v. 8) NSCLC and study
participants should not have had prior systemic therapy for advanced
disease.
2. Have confirmation that epidermal growth factor receptor– (EGFR-),
anaplastic lymphoma kinase– (ALK-), c-ros oncogene 1 (ROS1), or B
isoform of rapidly accelerated fibrosarcoma (B-Raf) directed therapy is not
indicated as primary therapy (documentation of absence of tumor activating
EGFR or B-Raf mutations AND absence of ALK or ROS1 gene
rearrangements). If participant’s tumor is known to have a predominantly
squamous histology, molecular testing for EGFR mutation and ALK and
ROS1 translocations will not be required, as this is not part of current
diagnostic guidelines.
3. Have measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology. Lesions situated in a previously irradiated area are
considered measurable if progression has been demonstrated in such
lesions.
4. Male/female subjects who are at least 18 years of age on the day of signing
the informed consent.
5. A male participant must agree to use a contraceptive as detailed in Protocol
Appendix 5 of this protocol during the treatment period and for at least 120
days after the last dose of study treatment and refrain from donating sperm
during this period.
6. A female participant is eligible to participate if she is not pregnant (see
Protocol Appendix 5), not breastfeeding, and at least one of the following
conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in Protocol
Appendix 5
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in Protocol
Appendix 5 during the treatment period and for at least 120 days after the
last dose of study treatment.
7. The participant (or legally acceptable representative if applicable) provides
written informed consent for the study. The participant may also provide
consent for Future Biomedical Research. However, the participant may
participate in the main study without participating in Future Biomedical
Research.
8. Have provided archival tumor tissue sample or newly obtained core or
excisional biopsy of a tumor lesion not previously irradiated. Newly
obtained biopsies are preferred to archival tissue. Repeat samples may be
required if adequate tissue is not provided.
9. Participants must have adequately controlled blood pressure (BP) with or
without antihypertensive medications, defined as BP ≤150/90 mm Hg at
Screening and no change in antihypertensive medications within 1 week
before Cycle 1/Day 1.
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 to 1.
11. Have adequate organ function. Specimens must be collected within 10 days
prior to the start of study treatment.
Exclusion Criteria
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1. Has significant cardiovascular impairment within 12 months of the first
dose of study drug: such as history of congestive heart failure greater than
New York Heart Association (NYHA) Class II, unstable angina, myocardial
infarction or cerebrovascular accident (CVA) stroke, cardiac arrhythmia
associated with hemodynamic instability, or a left ventricular ejection
fraction (LVEF) below the institutional normal range as determined by
multigated acquisition scan (MUGA) or echocardiogram.
2. Prolongation of QTc interval to >480 ms.
3. Has symptomatic ascites or pleural effusion. A participant who is clinically
stable following treatment for these conditions (including therapeutic
thoraco- or paracentesis) is eligible.
4. Has had an allogenic tissue/solid organ transplant.
5. A WOCBP who has a positive urine pregnancy test within 72 hours before
the first dose of study treatment (see Protocol Appendix 5). If the urine
test cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the
screening pregnancy test and the first dose of study treatment, another
pregnancy test (urine or serum) must be performed and must be negative in
order for subject to start receiving study medication.
6. Subjects with proteinuria >1+ on urine dipstick testing will undergo
24-hour urine collection for quantitative assessment of proteinuria. Subjects
with urine protein ≥1 g/24 h will be ineligible.
7. Subjects who have not recovered adequately from any toxicity and/or
complications from major surgery prior to starting therapy.
8. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
condition that might affect the absorption of lenvatinib
9. Radiographic evidence of major blood vessel invasion/infiltration. The
degree of tumor invasion/infiltration of major blood vessels should be
considered because of the potential risk of severe hemorrhage associated
with tumor shrinkage/necrosis following lenvatinib therapy.
10. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to
the first dose of study drug.
11. Has received prior systemic chemotherapy treatment for
metastatic/recurrent NSCLC.
12. Has current NSCLC disease that can be treated with curative intent with
surgical resection, localized radiotherapy, or chemoradiation.
13. Is expected to require any other form of systemic or localized
antineoplastic therapy while on study (including maintenance therapy with
another agent for NSCLC, radiation therapy, and/or surgical resection).
14. Has received prior therapy with an anti–PD-1, anti–PD-L1, or anti–PD-L2
agent or with an agent directed to another stimulatory or co-inhibitory T
cell receptor (eg, CTLA-4, OX 40, CD137).
15. Has received previous treatment with another agent targeting the LAG3
receptor.
16. Has received previous treatment with another agent targeting VEGF or the
VEGF receptor.
17. Has received prior anticancer therapy including investigational agents
within 4 weeks prior to randomization.
18. Has received prior radiotherapy within 3 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not
require corticosteroids, and not have had radiation pneumonitis. A
1-week washout is permitted for palliative radiation (≤2 weeks of
radiotherapy) to non-CNS disease.
Participants are excluded from the study if any of the following criteria apply:
1. Has significant cardiovascular impairment within 12 months of the first
dose of study drug: such as history of congestive heart failure greater than
New York Heart Association (NYHA) Class II, unstable angina, myocardial
infarction or cerebrovascular accident (CVA) stroke, cardiac arrhythmia
associated with hemodynamic instability, or a left ventricular ejection
fraction (LVEF) below the institutional normal range as determined by
multigated acquisition scan (MUGA) or echocardiogram.
2. Prolongation of QTc interval to >480 ms.
3. Has symptomatic ascites or pleural effusion. A participant who is clinically
stable following treatment for these conditions (including therapeutic
thoraco- or paracentesis) is eligible.
4. Has had an allogenic tissue/solid organ transplant.
5. A WOCBP who has a positive urine pregnancy test within 72 hours before
the first dose of study treatment (see Protocol Appendix 5). If the urine
test cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the
screening pregnancy test and the first dose of study treatment, another
pregnancy test (urine or serum) must be performed and must be negative in
order for subject to start receiving study medication.
6. Subjects with proteinuria >1+ on urine dipstick testing will undergo
24-hour urine collection for quantitative assessment of proteinuria. Subjects
with urine protein ≥1 g/24 h will be ineligible.
7. Subjects who have not recovered adequately from any toxicity and/or
complications from major surgery prior to starting therapy.
8. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
condition that might affect the absorption of lenvatinib
9. Radiographic evidence of major blood vessel invasion/infiltration. The
degree of tumor invasion/infiltration of major blood vessels should be
considered because of the potential risk of severe hemorrhage associated
with tumor shrinkage/necrosis following lenvatinib therapy.
10. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to
the first dose of study drug.
11. Has received prior systemic chemotherapy treatment for
metastatic/recurrent NSCLC.
12. Has current NSCLC disease that can be treated with curative intent with
surgical resection, localized radiotherapy, or chemoradiation.
13. Is expected to require any other form of systemic or localized
antineoplastic therapy while on study (including maintenance therapy with
another agent for NSCLC, radiation therapy, and/or surgical resection).
14. Has received prior therapy with an anti–PD-1, anti–PD-L1, or anti–PD-L2
agent or with an agent directed to another stimulatory or co-inhibitory T
cell receptor (eg, CTLA-4, OX 40, CD137).
15. Has received previous treatment with another agent targeting the LAG3
receptor.
16. Has received previous treatment with another agent targeting VEGF or the
VEGF receptor.
17. Has received prior anticancer therapy including investigational agents
within 4 weeks prior to randomization.
18. Has received prior radiotherapy within 3 weeks of start of study treatment.
Participants must have recovered from all radiation-related toxicities, not
require corticosteroids, and not have had radiation pneumonitis. A
1-week washout is permitted for palliative radiation (≤2 weeks of
radiotherapy) to non-CNS disease.
The Estimated Number of Participants
-
Taiwan
12 participants
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Global
288 participants
