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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT06036836

Studienbeginn:
September 2023

Letztes Update:
21.06.2024

Wirkstoff:
Favezelimab/Pembrolizumab, Pembrolizumab, Lenvatinib

Indikation (Clinical Trials):
Endometrial Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 42)

Universitaetsklinikum Essen-Klinik für Dermatologie, Venerologie und Allergologie ( Site 0182)
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 492017232431» Ansprechpartner anzeigen
UT Southwestern Medical Center-CRO-Simmons Comprehensive Cancer Center ( Site 0645)
75390-9179 Dallas
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 214-645-0595» Ansprechpartner anzeigen
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
G1J 1Z4 Quebec City
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 15147123215» Ansprechpartner anzeigen
Fondazione IRCCS Istituto Nazionale dei Tumori-SC Oncologia Medica 3 - Tumori Testa-collo ( Site 025
20133 Milan
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 0039 0223903352» Ansprechpartner anzeigen
Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi
80131 Napoli
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 390815903431» Ansprechpartner anzeigen
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0423)
34722 Istanbul
TurkeyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 00905063509061» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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].

Ein-/Ausschlusskriterien

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

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

Studien-Rationale

Primary outcome:

1. Pathological Complete Response (pCR) - Cohort A (Time Frame - Up to approximately 22 months):
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.

2. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Investigator - Cohort B (Time Frame - Up to approximately 21 months):
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:

1. Overall Survival (OS) - All Cohorts (Time Frame - Up to approximately 41 months):
OS is defined as the time from randomization to death from any cause.

2. Clinical Benefit Rate - Cohort A (Time Frame - Up to approximately 22 months):
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.

3. Event-Free Survival (EFS) - Cohort A (Time Frame - Up to approximately 41 months):
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.

4. Major Pathological Response (mPR) - Cohort A (Time Frame - Up to approximately 22 months):
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.

5. ORR per RECIST 1.1 as assessed by Investigator - Cohort A (Time Frame - Up to approximately 22 months):
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.

6. Number of participants with an adverse event (AE) - Cohorts A and B (Time Frame - Up to approximately 41 months):
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.

7. Number of participants discontinuing from study therapy due to AE - Cohorts A and B (Time Frame - Up to approximately 41 months):
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.

8. Number of participants experiencing perioperative complications - Cohort A (Time Frame - Up to approximately 18 weeks):
The number of participants who experience perioperative complications will be assessed.

9. Number of participants with an AE that precludes surgery/initiation of adjuvant therapy - Cohort A (Time Frame - Up to approximately 2 months):
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.

10. Progression Free Survival (PFS) - Cohort B (Time Frame - Up to approximately 41 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 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.

11. Duration of Response (DOR) - Cohort B (Time Frame - Up to approximately 41 months):
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.

Studien-Arme

  • 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.

Geprüfte Regime

  • favezelimab/pembrolizumab (MK-4280A):
    IV infusion
  • pembrolizumab (MK-3475 / Keytruda® / ):
    IV infusion
  • lenvatinib:
    Oral administration of capsule

Quelle: ClinicalTrials.gov


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