History of Changes for Study: NCT05609968

Study of Pembrolizumab (MK-3475) Monotherapy Versus Sacituzumab Govitecan in Combination With Pembrolizumab for Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-3475-D46)

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Study Record Versions

Version	Submitted Date	Changes
1	November 2, 2022	None (earliest Version on record)
2	January 13, 2023	Recruitment Status, Study Status, Contacts/Locations and References
3	January 27, 2023	Contacts/Locations and Study Status
4	February 3, 2023	Study Status and Contacts/Locations
5	February 9, 2023	Contacts/Locations, Study Status and Study Identification
6	February 17, 2023	Study Status and Contacts/Locations
7	February 26, 2023	Contacts/Locations and Study Status
8	March 2, 2023	Study Status and Contacts/Locations
9	March 16, 2023	Contacts/Locations and Study Status
10	April 10, 2023	Contacts/Locations and Study Status
11	April 13, 2023	Contacts/Locations and Study Status
12	April 21, 2023	Contacts/Locations and Study Status
13	May 3, 2023	Contacts/Locations, Study Status and Study Identification
14	May 15, 2023	Contacts/Locations and Study Status
15	May 19, 2023	Contacts/Locations and Study Status
16	May 26, 2023	Contacts/Locations and Study Status
17	June 6, 2023	Contacts/Locations and Study Status
18	June 21, 2023	Contacts/Locations and Study Status
19	July 6, 2023	References, Contacts/Locations and Study Status
20	July 19, 2023	Contacts/Locations and Study Status
21	August 10, 2023	Contacts/Locations and Study Status
22	August 18, 2023	Contacts/Locations and Study Status
23	September 8, 2023	Contacts/Locations and Study Status
24	October 6, 2023	Contacts/Locations and Study Status
25	October 12, 2023	Contacts/Locations and Study Status
26	October 18, 2023	Contacts/Locations and Study Status
27	October 26, 2023	Contacts/Locations and Study Status
28	November 3, 2023	Study Status and Contacts/Locations
29	November 5, 2023	References and Study Status
30	November 8, 2023	Contacts/Locations and Study Status
31	November 16, 2023	Contacts/Locations and Study Status
32	December 1, 2023	Contacts/Locations and Study Status
33	December 7, 2023	Contacts/Locations and Study Status
34	December 15, 2023	Contacts/Locations and Study Status
35	January 18, 2024	Contacts/Locations and Study Status
36	January 25, 2024	Contacts/Locations and Study Status
37	February 8, 2024	Contacts/Locations and Study Status
38	March 7, 2024	Contacts/Locations and Study Status
39	April 4, 2024	Contacts/Locations and Study Status
40	May 9, 2024	Contacts/Locations and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	3475-D46
Brief Title:	Study of Pembrolizumab (MK-3475) Monotherapy Versus Sacituzumab Govitecan in Combination With Pembrolizumab for Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-3475-D46)
Official Title:	An Open-label, Multicenter, Phase 3 Randomized, Active-Comparator-Controlled Clinical Study of Pembrolizumab (MK-3475) in Combination With Sacituzumab Govitecan Versus MK-3475 Monotherapy as First-line Treatment in Participants With PD L1 TPS Greater Than or Equal to 50% Metastatic Non-small Cell Lung Cancer (KEYNOTE D46/EVOKE-03)
Secondary IDs:	MK-3475-D46 [Merck] 2022-000836-49 [EudraCT Number]

Study Status


Record Verification:	October 2022
Overall Status:	Not yet recruiting
Study Start:	December 16, 2022
Primary Completion:	January 12, 2027 [Anticipated]
Study Completion:	August 23, 2028 [Anticipated]

First Submitted:	November 2, 2022
First Submitted that Met QC Criteria:	November 2, 2022
First Posted:	November 8, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	November 2, 2022
Last Update Posted:	November 8, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Merck Sharp & Dohme LLC
Responsible Party:	Sponsor
Collaborators:	Gilead Sciences

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description

Brief Summary:

The purpose of this study is to compare pembrolizumab (MK-3475) in combination with sacituzumab govitecan with pembrolizumab alone with respect to progression-free survival (PFS) and overall survival (OS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) among adults with metastatic non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%).

Detailed Description:

Conditions


Conditions:	Carcinoma, Non-Small-Cell Lung
Keywords:	Programmed Cell Death-1 (PD1, PD-1) Programmed Death-Ligand 1 (PDL1, PD-L1) Programmed Cell Death-2 (PD2, PD-2) Programmed Death-Ligand 2 (PDL2, PD-L2) Trophoblast Cell Surface Antigen-2 (TROP-2) Antibody-Drug Conjugate (ADC)

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	614 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

Experimental: Pembrolizumab + Sacituzumab Govitecan

Participants receive sacituzumab govitecan 10mg/kg intravenous (IV) infusion once weekly on Day 1 and Day 8 of a continuous 21-day cycle until progressive disease (PD) requiring discontinuation, unacceptable toxicity, withdrawal of consent, or death. Participants receive pembrolizumab 200mg IV infusion on Day 1 every 3 weeks (Q3W) for up to 35 cycles (each cycle length = 21 days).

Biological: Sacituzumab Govitecan

IV infusion

Other Names:

Trodelvy®

Biological: Pembrolizumab

IV infusion

Other Names:

MK-3475
Keytruda®

Experimental: Pembrolizumab

Participants receive pembrolizumab 200mg IV infusion on Day 1 Q3W for up to 35 cycles (each cycle length = 21 days).

Biological: Pembrolizumab

IV infusion

Other Names:

MK-3475
Keytruda®

Outcome Measures


Primary Outcome Measures:
1.	Progression-Free Survival (PFS) [ Time Frame: Up to approximately 34 months ] PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as per the Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the 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 is modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by blinded independent central review (BICR) will be presented.
2.	Overall Survival (OS) [ Time Frame: Up to approximately 48 months ] OS is defined as the time from randomization to death due to any cause.
Secondary Outcome Measures:
1.	Objective Response (OR) [ Time Frame: Up to approximately 34 months ] OR is defined as the confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 by BICR.
2.	Duration of Response (DOR) [ Time Frame: Up to approximately 48 months ] DOR is defined as the time from the first documented evidence of a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.
3.	Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline and up to approximately 48 months ] The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" will be scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better overall health status. Per protocol, the change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.
4.	Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 48 months ] The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better level of physical functioning. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.
5.	Change from Baseline in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 48 months ] The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a better level of role functioning. Change from baseline in the role functioning (EORTC QLQ-C30 Items 6-7) combined score will be presented.
6.	Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 48 months ] The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicates a worse level of dyspnea. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented.
7.	Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline and up to approximately 48 months ] The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate more frequent coughing and a worse outcome. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented.
8.	Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 [ Time Frame: Baseline and up to approximately 48 months ] The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate worse level of chest pain. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented.
9.	Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30 [ Time Frame: Up to approximately 48 months ] The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") will be scored on a 7-point scale (1=Very Poor to 7=Excellent). Higher scores indicate a better overall outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Items 29 and 30 will be presented.
10.	TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 [ Time Frame: Up to approximately 48 months ] The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better level of physical functioning. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Items 1-5 will be presented.
11.	TTD in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30 [ Time Frame: Up to approximately 48 months ] The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a better level of role functioning. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Items 6-7 will be presented.
12.	TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 11 [ Time Frame: Up to approximately 48 months ] The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-C30 Item 8 will be presented.
13.	TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 [ Time Frame: Up to approximately 48 months ] The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate more frequent coughing and a worse outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-LC13 Item 31 will be presented.
14.	TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 [ Time Frame: Up to approximately 48 months ] The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores indicate worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. TTD in the score of EORTC QLQ-LC13 Item 40 will be presented.
15.	Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 48 months ] An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study intervention. Per protocol, the number of participants who experience an AE will be reported.
16.	Number of Participants Who Discontinue Study Treatment Due To an AE [ Time Frame: Up to approximately 48 months ] An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study intervention. Per protocol, the number of participants who discontinue study treatment due to an AE will be reported.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: The main inclusion criteria include but are not limited to the following: Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC) Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase 1 (ALK-1), or ROS proto-oncogene 1 (ROS-1)-directed therapy is not indicated as primary therapy Has provided tumor tissue that demonstrates PD-L1 tumor proportion score (TPS) ≥50% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory Has a life expectancy of at least 3 months Exclusion Criteria: The main exclusion criteria include but are not limited to the following: Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC Has previously received treatment with Topoisomerase 1 inhibitors or Trop-2 targeted therapy Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study intervention Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration Has cardiac disease Myocardial infarction or unstable angina pectoris within 6 months of enrollment History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications; history of QT interval prolongation New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of <40% Has active chronic inflammatory bowel disease Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis Has severe hypersensitivity (≥Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease Has active infection requiring systemic therapy Has history of human immunodeficiency virus (HIV) infection History of hepatitis B or known active hepatitis C virus infection Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator Have not adequately recovered from major surgery or have ongoing surgical complications

Contacts/Locations


Study Officials:	Medical Director Study Director Merck Sharp & Dohme LLC
Locations:

IPDSharing


Plan to Share IPD:	Yes http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL: http://engagezone.msd.com/ds_documentation.php

References


Citations:
Links:
Available IPD/Information: