Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06036836




Registration number
NCT06036836
Ethics application status
Date submitted
21/08/2023
Date registered
14/09/2023
Date last updated
19/11/2024

Titles & IDs
Public title
Study of Favezelimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010)
Scientific 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 (KeyForm-010)
Secondary ID [1] 0 0
MK-4280A-010
Secondary ID [2] 0 0
4280A-010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Cutaneous Squamous Cell Carcinoma 0 0
Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - favezelimab/pembrolizumab
Treatment: Other - pembrolizumab
Treatment: Drugs - lenvatinib

Experimental: Favezelimab/Pembrolizumab - Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via an intravenous (IV) infusion every 3 weeks (Q3W) for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.

Experimental: Pembrolizumab - Participants will receive 200 mg pembrolizumab via an IV infusion Q3W for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.

Experimental: Favezelimab/Pembrolizumab + Lenvatinib (Cohort B) - 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.

Experimental: Pembrolizumab + Lenvatinib (Cohort B) - 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.


Treatment: Other: favezelimab/pembrolizumab
IV infusion

Treatment: Other: pembrolizumab
IV infusion

Treatment: Drugs: lenvatinib
Oral administration of capsule
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathologic Complete Response (pCR) - Cohort A
Timepoint [1] 0 0
Up to approximately 22 months
Primary outcome [2] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B
Timepoint [2] 0 0
Up to approximately 21 months
Secondary outcome [1] 0 0
Overall Survival (OS) - All Cohorts
Timepoint [1] 0 0
Up to approximately 41 months
Secondary outcome [2] 0 0
Clinical Benefit Rate - Cohort A
Timepoint [2] 0 0
Up to approximately 22 months
Secondary outcome [3] 0 0
Event-Free Survival (EFS) - Cohort A
Timepoint [3] 0 0
Up to approximately 41 months
Secondary outcome [4] 0 0
Major Pathologic Response (mPR) - Cohort A
Timepoint [4] 0 0
Up to approximately 22 months
Secondary outcome [5] 0 0
ORR per RECIST 1.1 as assessed by Investigator - Cohort A
Timepoint [5] 0 0
Up to approximately 22 months
Secondary outcome [6] 0 0
Number of participants with an adverse event (AE) - Cohorts A and B
Timepoint [6] 0 0
Up to approximately 41 months
Secondary outcome [7] 0 0
Number of participants discontinuing from study therapy due to AE - Cohorts A and B
Timepoint [7] 0 0
Up to approximately 41 months
Secondary outcome [8] 0 0
Number of participants experiencing perioperative complications - Cohort A
Timepoint [8] 0 0
Up to approximately 18 weeks
Secondary outcome [9] 0 0
Number of participants with an AE that precludes surgery/initiation of adjuvant therapy - Cohort A
Timepoint [9] 0 0
Up to approximately 2 months
Secondary outcome [10] 0 0
Progression Free Survival (PFS) - Cohort B
Timepoint [10] 0 0
Up to approximately 41 months
Secondary outcome [11] 0 0
Duration of Response (DOR) - Cohort B
Timepoint [11] 0 0
Up to approximately 41 months

Eligibility
Key inclusion 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. 8
* 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 2009 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/03/2027
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital-The Kinghorn Cancer Centre ( Site 0005) - Darlinghurst
Recruitment hospital [2] 0 0
Royal North Shore Hospital ( Site 0008) - St Leonards
Recruitment hospital [3] 0 0
Blacktown Hospital ( Site 0003) - Sydney
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital ( Site 0002) - Brisbane
Recruitment hospital [5] 0 0
The Alfred Hospital ( Site 0004) - Melbourne
Recruitment hospital [6] 0 0
Fiona Stanley Hospital ( Site 0006) - Murdock
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2148 - Sydney
Recruitment postcode(s) [4] 0 0
4029 - Brisbane
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6150 - Murdock
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
France
State/province [10] 0 0
Alsace
Country [11] 0 0
France
State/province [11] 0 0
Finistere
Country [12] 0 0
France
State/province [12] 0 0
Rhone-Alpes
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
Germany
State/province [14] 0 0
Nordrhein-Westfalen
Country [15] 0 0
Germany
State/province [15] 0 0
Sachsen
Country [16] 0 0
Italy
State/province [16] 0 0
Lombardia
Country [17] 0 0
Italy
State/province [17] 0 0
Napoli
Country [18] 0 0
Malaysia
State/province [18] 0 0
Johor
Country [19] 0 0
Malaysia
State/province [19] 0 0
Kuala Lumpur
Country [20] 0 0
Malaysia
State/province [20] 0 0
Sarawak
Country [21] 0 0
Netherlands
State/province [21] 0 0
Gelderland
Country [22] 0 0
Netherlands
State/province [22] 0 0
Zuid-Holland
Country [23] 0 0
Netherlands
State/province [23] 0 0
Groningen
Country [24] 0 0
Taiwan
State/province [24] 0 0
Taichung
Country [25] 0 0
Taiwan
State/province [25] 0 0
Tainan
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taipei
Country [27] 0 0
Turkey
State/province [27] 0 0
Istanbul
Country [28] 0 0
Turkey
State/province [28] 0 0
Ankara

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate pathologic 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) \[Cohort B\].
Trial website
https://clinicaltrials.gov/study/NCT06036836
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06036836