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JOURNAL ONKOLOGIE – STUDIE

Efficacy, Safety, and Tolerability of V937 Administered Intravenously or Intratumorally With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone in Participants With Advanced/Metastatic Melanoma (V937-011)

Rekrutierend

NCT-Nummer:
NCT04152863

Studienbeginn:
Juni 2020

Letztes Update:
15.07.2021

Wirkstoff:
V937 IV, V937 ITu, Pembrolizumab

Indikation (Clinical Trials):
Melanoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 27)

Henry Ford Hospital ( Site 0008)
48202 Detroit
United StatesAbgeschlossen» Google-Maps
Rutgers Cancer Institute of New Jersey ( Site 0002)
08901 New Brunswick
United StatesAbgeschlossen» Google-Maps
Providence Portland Medical Center [Portland, OR] ( Site 0005)
97213 Portland
United StatesAbgeschlossen» Google-Maps
Northwest Medical Specialties, PLLC ( Site 0006)
98405 Tacoma
United StatesAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a Phase 2 study to assess the efficacy, safety, and tolerability of V937 administered

both intratumorally (ITu) and intravenously (IV) as combination therapy with pembrolizumab

(MK-3475) versus pembrolizumab alone in anti-programmed cell death ligand 1

(anti-PD-L1)-treatment-naive participants with advanced/metastatic melanoma. The primary

hypothesis of the study is that V937 administered either ITu or IV in combination with

pembrolizumab results in a superior objective response rate (ORR) per Response Evaluation

Criteria In Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review

(BICR), compared to pembrolizumab alone.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has histologically or cytologically confirmed diagnosis of advanced/metastatic

melanoma

- Has Stage III or Stage IV melanoma

- Must be naive to anti-PD-L1 treatment, talimogene laherparepvec (TVEC) and other

oncolytic viruses

- Has 2 lesions as defined below:

- At least 1 cutaneous or subcutaneous lesion that is amenable to IT injection and

biopsy and measurable per RECIST 1.1

- At least 1 distant and/or discrete noninjected lesion that is amenable to biopsy

and measurable per RECIST 1.1

- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)

Performance Scale

- Demonstrates adequate organ function

- Male participants refrain from donating sperm during the intervention period and for

at least 120 days after the last dose of study intervention PLUS are either abstinent

from heterosexual intercourse OR agree to use approved contraception during that

period

- Female participants are not pregnant or breastfeeding and are not a woman of

childbearing potential (WOCBP) OR are a WOCBP that agrees to use contraception during

the treatment and for at least 120 days after the last dose of study intervention

- Has measurable disease per RECIST 1.1

- Is able to provide newly obtained core or excisional biopsy of a tumor lesion not

previously irradiated

- Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV

on anti-retroviral therapy (ART), defined as:

- Must have Cluster of Differentiation 4 (CD4)+ T-cell count >350 cells/mm^3 at

time of screening

- Must have achieved and maintained virologic suppression

- Must have been on a stable regimen, without changes in drugs or dose

modification, for at least 4 weeks prior to study entry

- The combination ART regimen must not contain any antiretroviral medication other

than abacavir, dolutegravir, emtricitabine, lamivudine, raltegravir, rilpivirine,

or tenofovir

Exclusion Criteria:

- Has had chemotherapy, definitive radiation, or biological cancer therapy or an

investigational agent or investigational device within 4 weeks prior to the first dose

of study intervention or has not recovered to Common Terminology Criteria for Adverse

Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics

administered more than 4 weeks earlier

- Has ocular melanoma

- Has radiographic evidence of major blood vessel infiltration

- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the

first dose of study drug

- Has an active autoimmune disease that has required systemic treatment in the past 2

years except vitiligo or resolved childhood asthma/atopy

- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric

Castleman's Disease

- Has a known psychiatric or substance abuse disorder that would interfere with the

participant's ability to cooperate with the study requirements

- Has undergone allogeneic hematopoietic stem cell transplantation within the last 5

years

- Has not fully recovered from major surgery without significant detectable infection

- Active cardiovascular disease (<6 months prior to enrollment), myocardial infarction

(<6 months prior to enrollment), unstable angina, congestive heart failure or serious

cardiac arrhythmia requiring medication

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or other

agents such as cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), OX-40, Cluster of

Differentiation 137 (CD137)

- Has received a live vaccine within 30 days prior to the first dose of study drug

- Is currently participating in or has participated in a study of an investigational

agent or has used an investigational device within 4 weeks prior to the first dose of

study intervention

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

in excess of replacement doses or any other form of immunosuppressive therapy within 7

days prior the first dose of study drug

- Has a known additional malignancy that is progressing or has required active treatment

within the past 2 years

- Has known active central nervous system (CNS) metastases and/or carcinomatous

meningitis

- Has hypersensitivity to pembrolizumab and/or any of its excipients

- Has hypersensitivity to V937 or any of its excipients

- Has a history of (non-infectious) pneumonitis that required steroids or has current

pneumonitis

- Has an active infection requiring systemic therapy

- Has a known history of Hepatitis B or known active Hepatitis C virus infection

- Has a history or current evidence of any condition, therapy, or laboratory abnormality

that might confound the results of the study, interfere with the participant's

participation for the full duration of the study, or is not in the best interest of

the participant to participate, in the opinion of the treating investigator

- Has had an allogenic tissue/solid organ transplant

Studien-Rationale

Primary outcome:

1. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) (Time Frame - Up to 3 years):
ORR is defined as the percentage of participants who have a Complete Response (CR: disappearance of all lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions) as assessed by BICR per RECIST 1.1 which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.



Secondary outcome:

1. Progression-free Survival (PFS) per RECIST 1.1 as Assessed by BICR (Time Frame - Up to 3 years):
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as either a 20% increase from nadir in target lesions, unequivocal progression of non-target lesions, or the appearance of new lesions. PFS will be assessed by BICR for this outcome measure.

2. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR (Time Frame - Up to 3 years):
For participants who demonstrate a confirmed complete response (CR: disappearance of all lesions) or confirmed Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions, without evidence of progression based on non-target or new lesions.) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.

3. ORR per RECIST 1.1 as Assessed by the Investigator (Time Frame - Up to 3 years):
ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, without evidence of progression based on non-target or new lesions.) as assessed by the investigator per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.

4. PFS per RECIST 1.1 as Assessed by the Investigator (Time Frame - Up to 3 years):
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as either a 20% increase from nadir in target lesions, unequivocal progression of non-target lesions, or the appearance of new lesions. PFS will be assessed by the investigator for this outcome measure.

5. DOR per RECIST 1.1 as Assessed by the Investigator (Time Frame - Up to 3 years):
For participants who demonstrate a confirmed complete response (CR: disappearance of all lesions) or confirmed Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. DOR will be assessed by the investigator for this outcome measure.

6. Overall Survival (OS) (Time Frame - Up to 3 years):
OS is defined as the time from the date of study treatment to the date of death due to any cause.

7. Number of Participants with One or More Adverse Events (AEs) (Time Frame - Up to 30 days after last dose (up to 3 years)):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.

8. Number of Participants who Discontinue Study Drug Due to an AE (Time Frame - Up to 2 years):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.

Studien-Arme

  • Experimental: IV V937 + Pembrolizumab
    Participants receive V937 at a dose of 1 X 10^9 TCID50 by IV infusion on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. V937 will be administered for up to 8 cycles (up to 6 months). Pembrolizumab will be administered for up to 35 cycles (up to 2 years).
  • Experimental: ITu V937 + Pembrolizumab
    Participants receive V937 at a dose of 3 X 10^8 TCID50 by ITu injection on Days 1, 3, 5, and 8 of Cycle 1 (28-day cycle) and Day 1 of Cycles 2-8 (21-day cycles) plus pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. V937 will be administered for up to 8 cycles (up to 6 months). Pembrolizumab will be administered for up to 35 cycles (up to 2 years).
  • Experimental: Pembrolizumab
    Participants receive pembrolizumab 200 mg by IV infusion on Day 8 of Cycle 1 (28-day cycle) and Day 1 of each subsequent 21-day cycle. Pembrolizumab will be administered for up to 35 cycles (up to 2 years).

Geprüfte Regime

  • V937 IV (Coxsackievirus A21 (CVA21) / Formerly known as CAVATAK® / CAV21 / ):
    Administered as an IV infusion of 1 X 10^9 TCID50
  • V937 ITu (Coxsackievirus A21 (CVA21) / Formerly known as CAVATAK® / CAV21 / ):
    Administered as an ITu injection of 3 X 10^8 TCID50
  • Pembrolizumab (MK-3475 / Keytruda® / ):
    Administered as an IV infusion of 200 mg

Quelle: ClinicalTrials.gov


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