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JOURNAL ONKOLOGIE – STUDIE

Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYNOTE-01A)

Rekrutierend

NCT-Nummer:
NCT04165070

Studienbeginn:
Dezember 2019

Letztes Update:
14.01.2021

Wirkstoff:
Pembrolizumab, Carboplatin, Paclitaxel, Pemetrexed, Vibostolimab

Indikation (Clinical Trials):
Carcinoma, Non-Small-Cell Lung

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 21)

Alle anzeigen

Studien-Informationen

Detailed Description:

The Master screening protocol is MK-3475-U01 - NCT04165798

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or

nonsquamous NSCLC

- Participants with nonsquamous NSCLC who are not eligible for an approved targeted

therapy

- Is able to provide archival tumor tissue sample or newly obtained core or excisional

biopsy of a tumor lesion not previously irradiated

- Has not received prior systemic treatment for their metastatic NSCLC

- Is able to complete all screening procedures within the 28-day screening window

- Has adequate organ function within 10 days of initiation of study treatment

- Male participants must agree to use contraception and should refrain from donating

sperm during the treatment period and for at least 120 days after the last dose of

pembrolizumab and for at least 180 days after the last dose of chemotherapy

- Female participants must not be pregnant or breastfeeding, and at least one of the

following conditions apply:

1. Not a woman of childbearing potential (WOCBP), OR

2. A WOCBP who agrees to use contraception during the treatment period and for at

least 120 days after the last dose of pembrolizumab and for at least 180 days

after the last dose of chemotherapy

Exclusion Criteria:

- Has a diagnosis of small cell lung cancer

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

(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of

immunosuppressive therapy within 7 days prior to the first dose of study treatment

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

years

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

pneumonitis

- Has an active infection requiring systemic therapy

- Has clinically significant cardiac disease, including unstable angina, acute

myocardial infarction within 6 months from Day 1 of study treatment administration, or

New York Heart Association Class III or IV congestive heart failure

- Has a known history of HIV infection

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

- Has had major surgery <3 weeks prior to first dose of study treatment

- Is expected to require any other form of antineoplastic therapy while on study

- Has symptomatic ascites or pleural effusion (if receiving pemetrexed; Alimta®, Eli

Lilly)

- Has a history or current evidence of a gastrointestinal (GI) condition (e.g.

inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver

function or diseases that in the opinion of the investigator may significantly alter

the absorption or metabolism of oral medications

- Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal

abscess, GI obstruction, or peritoneal carcinomatosis

- Has pre-existing neuropathy that is moderate in intensity

- Has received prior systemic cytotoxic chemotherapy or other targeted or biological

antineoplastic therapy for metastatic disease

- Has received prior therapy with an anti-programmed cell death-1 (PD-1),

anti-programmed cell death-ligand 1 (PD-L1), or anti-PD-L2 agent or prior therapy

targeting other immunoregulatory receptors or mechanisms

- Is currently receiving either strong or moderate inhibitors of cytochrome P450 3A4

(CYP3A4) or cytochrome P450 2C8 (CYP2C8) that cannot be discontinued for the duration

of the study

- Is currently receiving strong or moderate inducers of CYP3A4 or CYP2C8 that cannot be

discontinued for the duration of the study

- Is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs

(NSAIDs), other than aspirin dose less than or equal to 1.3 gm/day for a 5-day period

(8-day period for long acting agents such as peroxicam), for participants who will

receive pemetrexed

- Is unable or unwilling to take folic acid or vitamin B12 supplementation, for

participants who will receive pemetrexed

- Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any

of their excipients

- Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months

of the first dose of study treatment

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

- Has received any prior immunotherapy and was discontinued from that treatment due to a

severe or worse immune-related adverse event (irAE)

- 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 treatment

- Previously had a severe hypersensitivity reaction to treatment with monoclonal

antibodies (including pembrolizumab) and/or any of their excipients

- Is pregnant or breastfeeding or expecting to conceive or father children within the

projected duration of the study, starting with the screening visit through 120 days

after the last dose of study treatment

- Has had an allogenic tissue/solid organ transplant

Studien-Rationale

Primary outcome:

1. Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Time Frame - Up to approximately 24 months):
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.



Secondary outcome:

1. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Time Frame - Up to approximately 24 months):
PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per 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.

2. Number of Participants Who Experience One or More Adverse Events (AEs) (Time Frame - Up to approximately 27 months):
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

3. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) (Time Frame - Up to approximately 24 months):
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

Studien-Arme

  • Experimental: Pembrolizumab + Vibostolimab + Carboplatin + Paclitaxel
    On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).
  • Experimental: Pembrolizumab + Vibostolimab + Pemetrexed
    On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).

Geprüfte Regime

  • Pembrolizumab (MK-3475 / SCH 900475 / KEYTRUDA® / ):
    IV infusion
  • Carboplatin (PARAPLATIN®):
    IV infusion
  • Paclitaxel (ABRAXANE®):
    IV infusion
  • Pemetrexed (ALIMTA®):
    IV infusion
  • Vibostolimab (MK-7684):
    IV infusion

Quelle: ClinicalTrials.gov


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