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Study of Favelizimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)

Primary Purpose

Solid Tumor, Cutaneous Squamous Cell Carcinoma, Endometrial Cancer

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
favezelimab/pembrolizumab
pembrolizumab
lenvatinib
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death-2 (PD2, PD-2), Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2), Lymphocyte-Activation Gene 3 (LAG-3)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Cohort A only Histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted) Stage II to Stage IV disease without distant metastasis (M1). cSCC tumors arising in the head and neck will be staged according to American Joint Committee on Cancer (AJCC) Edition (Ed.) 8 and cSCC tumors arising in non-head and neck locations will be staged according to Union for International Cancer Control (UICC) Ed. 9 Is systemic treatment naïve Archival tumor tissue sample, or newly obtained surgical resection, or biopsy sample of a tumor lesion not previously irradiated has been provided Is an individual of any sex/gender, at least 18 years of age at the time of providing the informed consent Cohort B only Histologically confirmed diagnosis of endometrial cancer (EC) that is not deficient in mismatch repair (dMMR) proficient in mismatch repair (pMMR) as documented by a local test report Documented evidence of stage IVB (per International Federation of Gynecology and Obstetrics (FIGO) staging), recurrent, or metastatic EC, and are not candidates for curative surgery or radiation Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC in any setting Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) by investigator (before first dose of study intervention) Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent Has adequately controlled blood pressure without antihypertensive medication All Cohorts Agrees to follow contraception guidelines if a participant of childbearing potential Has a life expectancy >3 years per investigator assessment Has adequate organ function Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 If positive for hepatitis B, has received antiviral therapy for ≥4 weeks and undetectable viral load prior to randomization If positive for hepatitis C, has undetectable viral load at screening If positive for human immunodeficiency virus (HIV), has well-controlled HIV on a stable highly active antiretroviral therapy Exclusion Criteria: All Cohorts Has known hypersensitivity to active substances or their excipients including previous clinically significant hypersensitivity reaction to treatment with other monoclonal antibody (mAb) History of allogeneic tissue/solid organ transplant Cohort A only Received prior radiotherapy to the index lesion (in-field lesion) Participants for whom the primary site of cSCC was anogenital area (penis, scrotum, vulva, perianal region) are not eligible Cohort B Has had major surgery within 3 weeks prior to first dose of study interventions Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula Has urine protein ≥1 g/24 hours Has a left ventricle ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multi-gated acquisition (MUGA) or echocardiogram (ECHO) Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation Has clinically significant cardiovascular disease within 12 months from first dose of study intervention

Sites / Locations

  • Blacktown Hospital ( Site 0003)Recruiting
  • National Cheng Kung University Hospital-Clinical Trial Center ( Site 0032)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Favezelimab/Pembrolizumab

Pembrolizumab

Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)

Pembrolizumab + Lenvatinib (Cohort B)

Arm Description

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via an intravenous (IV) infusion every 3 weeks (Q3W) for up to 3 cycles in the neoadjuvant period and up to 14 cycles of adjuvant therapy. Each cycle is 21 days.

Participants will receive 200 mg pembrolizumab via an IV infusion Q3W for up to 3 cycles in the neoadjuvant period and up to 14 cycles of adjuvant therapy. Each cycle is 21 days.

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib every day (QD) 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.

Participants will receive 200 mg pembrolizumab via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib QD 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.

Outcomes

Primary Outcome Measures

Pathological Complete Response (pCR) - Cohort A
pCR is defined as complete absence of viable tumor in the surgical resection sample as assessed by central review of the pathology results. Number of Cohort A participants with pCR will be reported.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B
The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

Secondary Outcome Measures

Overall Survival (OS) - All Cohorts
OS is defined as the time from randomization to death from any cause.
Clinical Benefit Rate - Cohort A
Clinical benefit rate is defined as the percentage of participants who have clinical benefit. Clinical benefit is defined as pCR in participants who undergo surgery or clinical complete response (cCR) [defined as residual tumor not visible on clinical exam or on imaging and a negative biopsy, if biopsy is available, in participants who decline surgery.
Event-Free Survival (EFS) - Cohort A
EFS is defined as the time from randomization to first progression prior to surgical resection as assessed by investigator, inability to resect tumor, recurrence (postsurgical resection), or death from any cause, whichever occurs first.
Major Pathological Response (mPR) - Cohort A
mPR is defined as ≤10% of viable tumor cells in the surgical resection sample as assessed by central review of the pathology results. The number of Cohort A participants with mPR will be reported.
ORR per RECIST 1.1 as assessed by Investigator - Cohort A
The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Number of participants with an adverse event (AE) - Cohorts A and B
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who experience an AE will be reported.
Number of participants discontinuing from study therapy due to AE - Cohorts A and B
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be reported.
Number of participants experiencing perioperative complications - Cohort A
The number of participants who experience perioperative complications will be assessed.
Number of participants with an AE that precludes surgery/initiation of adjuvant therapy - Cohort A
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of Cohort A participants with an AE that precludes surgery or initiation of adjuvant therapy will be reported.
Progression Free Survival (PFS) - Cohort B
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 assessed by the investigator. Per RECIST 1.1, or by histopathologic confirmation of disease progression (PD), 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. Unequivocal progression of non-target lesions is also considered PD.
Duration of Response (DOR) - Cohort B
DOR is defined as the time from first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. 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. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.

Full Information

First Posted
August 21, 2023
Last Updated
October 6, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT06036836
Brief Title
Study of Favelizimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)
Official Title
A Multicenter, Randomized, Double-Blind, Phase 2, Basket Study of MK-4280A, a Coformulation of Favezelimab (MK-4280) With Pembrolizumab (MK-3475) in Selected Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 29, 2023 (Actual)
Primary Completion Date
March 9, 2027 (Anticipated)
Study Completion Date
March 9, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate pathological complete response (pCR) rate of coformulated favezelimab/pembrolizumab (MK-4280A) or pembrolizumab as assessed by blinded central pathology review (BICR) in participants with cutaneous squamous cell carcinoma (cSCC) [Cohort A] and to evaluate lenvatinib in combination with coformulated favezelimab/pembrolizumab or pembrolizumab with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator in participants proficient in mismatch repair (pMMR) endometrial cancer (EC) [Cohort B].

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Cutaneous Squamous Cell Carcinoma, Endometrial Cancer
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death-2 (PD2, PD-2), Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2), Lymphocyte-Activation Gene 3 (LAG-3)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Favezelimab/Pembrolizumab
Arm Type
Experimental
Arm Description
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via an intravenous (IV) infusion every 3 weeks (Q3W) for up to 3 cycles in the neoadjuvant period and up to 14 cycles of adjuvant therapy. Each cycle is 21 days.
Arm Title
Pembrolizumab
Arm Type
Experimental
Arm Description
Participants will receive 200 mg pembrolizumab via an IV infusion Q3W for up to 3 cycles in the neoadjuvant period and up to 14 cycles of adjuvant therapy. Each cycle is 21 days.
Arm Title
Favezelimab/Pembrolizumab + Lenvatinib (Cohort B)
Arm Type
Experimental
Arm Description
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib every day (QD) 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.
Arm Title
Pembrolizumab + Lenvatinib (Cohort B)
Arm Type
Experimental
Arm Description
Participants will receive 200 mg pembrolizumab via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib QD 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.
Intervention Type
Biological
Intervention Name(s)
favezelimab/pembrolizumab
Other Intervention Name(s)
MK-4280A
Intervention Description
IV infusion
Intervention Type
Biological
Intervention Name(s)
pembrolizumab
Other Intervention Name(s)
MK-3475, Keytruda®
Intervention Description
IV infusion
Intervention Type
Drug
Intervention Name(s)
lenvatinib
Intervention Description
Oral administration of capsule
Primary Outcome Measure Information:
Title
Pathological Complete Response (pCR) - Cohort A
Description
pCR is defined as complete absence of viable tumor in the surgical resection sample as assessed by central review of the pathology results. Number of Cohort A participants with pCR will be reported.
Time Frame
Up to approximately 22 months
Title
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B
Description
The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time Frame
Up to approximately 21 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS) - All Cohorts
Description
OS is defined as the time from randomization to death from any cause.
Time Frame
Up to approximately 41 months
Title
Clinical Benefit Rate - Cohort A
Description
Clinical benefit rate is defined as the percentage of participants who have clinical benefit. Clinical benefit is defined as pCR in participants who undergo surgery or clinical complete response (cCR) [defined as residual tumor not visible on clinical exam or on imaging and a negative biopsy, if biopsy is available, in participants who decline surgery.
Time Frame
Up to approximately 22 months
Title
Event-Free Survival (EFS) - Cohort A
Description
EFS is defined as the time from randomization to first progression prior to surgical resection as assessed by investigator, inability to resect tumor, recurrence (postsurgical resection), or death from any cause, whichever occurs first.
Time Frame
Up to approximately 41 months
Title
Major Pathological Response (mPR) - Cohort A
Description
mPR is defined as ≤10% of viable tumor cells in the surgical resection sample as assessed by central review of the pathology results. The number of Cohort A participants with mPR will be reported.
Time Frame
Up to approximately 22 months
Title
ORR per RECIST 1.1 as assessed by Investigator - Cohort A
Description
The ORR is defined as the percentage of participants who have an OR per investigator assessment. The OR is defined as a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time Frame
Up to approximately 22 months
Title
Number of participants with an adverse event (AE) - Cohorts A and B
Description
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who experience an AE will be reported.
Time Frame
Up to approximately 41 months
Title
Number of participants discontinuing from study therapy due to AE - Cohorts A and B
Description
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be reported.
Time Frame
Up to approximately 41 months
Title
Number of participants experiencing perioperative complications - Cohort A
Description
The number of participants who experience perioperative complications will be assessed.
Time Frame
Up to approximately 18 weeks
Title
Number of participants with an AE that precludes surgery/initiation of adjuvant therapy - Cohort A
Description
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of Cohort A participants with an AE that precludes surgery or initiation of adjuvant therapy will be reported.
Time Frame
Up to approximately 2 months
Title
Progression Free Survival (PFS) - Cohort B
Description
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 assessed by the investigator. Per RECIST 1.1, or by histopathologic confirmation of disease progression (PD), 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. Unequivocal progression of non-target lesions is also considered PD.
Time Frame
Up to approximately 41 months
Title
Duration of Response (DOR) - Cohort B
Description
DOR is defined as the time from first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. 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. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time Frame
Up to approximately 41 months

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
Cohort A Only - Participant is an individual of any sex/gender Cohort B Only - Participant is assigned female sex at birth
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Cohort A only Histologically confirmed diagnosis of resectable cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted) Stage II to Stage IV disease without distant metastasis (M1). cSCC tumors arising in the head and neck will be staged according to American Joint Committee on Cancer (AJCC) Edition (Ed.) 8 and cSCC tumors arising in non-head and neck locations will be staged according to Union for International Cancer Control (UICC) Ed. 9 Is systemic treatment naïve Archival tumor tissue sample, or newly obtained surgical resection, or biopsy sample of a tumor lesion not previously irradiated has been provided Is an individual of any sex/gender, at least 18 years of age at the time of providing the informed consent Cohort B only Histologically confirmed diagnosis of endometrial cancer (EC) that is not deficient in mismatch repair (dMMR) proficient in mismatch repair (pMMR) as documented by a local test report Documented evidence of stage IVB (per International Federation of Gynecology and Obstetrics (FIGO) staging), recurrent, or metastatic EC, and are not candidates for curative surgery or radiation Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC in any setting Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) by investigator (before first dose of study intervention) Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent Has adequately controlled blood pressure without antihypertensive medication All Cohorts Agrees to follow contraception guidelines if a participant of childbearing potential Has a life expectancy >3 years per investigator assessment Has adequate organ function Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 If positive for hepatitis B, has received antiviral therapy for ≥4 weeks and undetectable viral load prior to randomization If positive for hepatitis C, has undetectable viral load at screening If positive for human immunodeficiency virus (HIV), has well-controlled HIV on a stable highly active antiretroviral therapy Exclusion Criteria: All Cohorts Has known hypersensitivity to active substances or their excipients including previous clinically significant hypersensitivity reaction to treatment with other monoclonal antibody (mAb) History of allogeneic tissue/solid organ transplant Cohort A only Received prior radiotherapy to the index lesion (in-field lesion) Participants for whom the primary site of cSCC was anogenital area (penis, scrotum, vulva, perianal region) are not eligible Cohort B Has had major surgery within 3 weeks prior to first dose of study interventions Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula Has urine protein ≥1 g/24 hours Has a left ventricle ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multi-gated acquisition (MUGA) or echocardiogram (ECHO) Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Blacktown Hospital ( Site 0003)
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
61298455200
Facility Name
National Cheng Kung University Hospital-Clinical Trial Center ( Site 0032)
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
886623535354559

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://www.merckclinicaltrials.com
Description
Merck Clinical Trials Information
URL
https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=4280A-010&kw=4280A-010
Description
Plain Language Summary

Learn more about this trial

Study of Favelizimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)

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