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JOURNAL ONKOLOGIE – STUDIE

Efficacy and Safety of Pembrolizumab (MK-3475) With Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage IIB or IIIA Non-small Cell Lung Cancer (MK-3475-671/KEYNOTE-671)

Rekrutierend

NCT-Nummer:
NCT03425643

Studienbeginn:
April 2018

Letztes Update:
15.03.2019

Wirkstoff:
Placebo, Pemetrexed, Cisplatin, Gemcitabine, Pembrolizumab

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations (3 von 138)

Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0053)
19124 Philadelphia
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 215-537-6438
» Ansprechpartner anzeigen
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0133)
J5402DIL San Juan
ArgentinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +542644211086
» Ansprechpartner anzeigen
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0530)
454087 Chelyabinsk
Russian FederationAbgeschlossen» Google-Maps
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0533)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79117500005
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

This trial will evaluate the safety and efficacy of pembrolizumab (MK-3475) in combination with platinum doublet neoadjuvant chemotherapy (NAC) before surgery [neoadjuvant phase], followed by pembrolizumab alone after surgery [adjuvant phase] in participants with resectable stage IIB or IIIA non-small cell lung cancer (NSCLC). The primary hypotheses of this study are that neoadjuvant pembrolizumab (vs. placebo) in combination with NAC, followed by surgery and adjuvant pembrolizumab (vs. placebo) will improve: 1) event free survival (EFS) by biopsy assessed by blinded central pathologist or by imaging using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) assessed by blinded independent central review (BICR); and 2) overall survival (OS).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Have previously untreated, histologically confirmed NSCLC and histologically confirmed Stage IIB or IIIA NSCLC.

- Be able to undergo protocol therapy, including necessary surgery.

- If male, must agree to use contraception or practice abstinence as well as refrain from donating sperm for at least 180 days after the last dose of study treatment.

- If female, may participate if not pregnant, not 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 follow contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment.

- Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for submission. If blocks are not available, have unstained slides for submission for central programmed death-ligand 1 (PD-L1) testing.

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days of randomization.

- Have adequate organ function.

Exclusion Criteria:

- A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment.

- Has one of the following tumor locations/types:1) NSCLC involving the superior sulcus; 2) Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.

- Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.

- Has an active infection requiring systemic therapy.

- Has had an allogenic tissue/sold organ transplant.

- Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients.

- Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.

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

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has a known history of Hepatitis B or Hepatitis C.

- Has a known history of active tuberculosis.

- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate.

- Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor.

- Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy prior to randomization/allocation.

- Has received prior radiotherapy within 2 weeks of start of trial treatment.

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

- Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.

- Has a diagnosis of immunodeficiency or is receiving either systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.

- Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.

- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment.

Studien-Rationale

Primary outcome:

1. Event Free Survival (EFS) (Time Frame - Up to 5 years):
EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by blinded central pathologist or by imaging using RECIST 1.1 assessed by BICR.

2. Overall Survival (OS) (Time Frame - Up to 5 years):
OS is defined as the time from randomization until death from any cause.

Secondary outcome:

1. Major Pathological Response (mPR) Rate (Time Frame - Up to 7 weeks following completion of neoadjuvant treatment (up to Study Week 20)):
mPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy.

2. Pathological Complete Response (pCR) Rate (Time Frame - Up to 7 weeks following completion of neoadjuvant treatment (up to Study Week 20)):
pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.

3. Global Health Status/Quality of Life (GHS/QoL) Score using the European Organization for Research and Treatment (EORTC) QoL Questionnaire (QLQ-C30) (Time Frame - Baseline (cycle 1 in neoadjuvant phase) and end of follow-up (up to 5 years)):
Change from baseline in GHS/QoL score using the EORTC QLQ-C30 will be determined. The EORTC QLQ-C30 is the most widely used cancer-specific, health-related QoL instrument comprised of 30 individual items arranged as both multi-item scales and individual items. Specifically, these items are divided into 5 functional scales (15 items total), 3 symptom scales (7 items total), 6 individual items, and a GHS/QoL scale composed of 2 items: GHS and QoL. The GHS/QoL score measured here refers to only the composite score calculated for the GHS/QoL scale. Both items on the GHS/QoL scale are scored from 1 (very poor GHS/QoL) to 7 (excellent GHS/QoL) and scores for both items are averaged and a linear transformation applied to standardize the overall GHS/QoL score from 0 to 100, with higher overall scores indicating higher GHS/QoL.

4. Adverse Events (AEs) (Time Frame - Up to 71 weeks):
The number of participants experiencing an AE will be assessed. An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

5. Perioperative Complications (Time Frame - Up to 51 weeks following surgery):
The number of participants experiencing perioperative complications will be assessed. Perioperative complications are a discrete set of both intraoperative and postoperative complications, potentially contributing to increased length of inpatient care and/or delay of adjuvant therapy.

6. Treatment Discontinuations Due to AEs (Time Frame - Up to 57 weeks):
The number of participants discontinuing study therapy due to an AE will be assessed.

Studien-Arme

  • Experimental: NAC + Neoadjuvant/Adjuvant Pembrolizumab
    Neoadjuvant: Prior to surgery, participants receive 4 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, intravenous (IV); given on cycle day 1] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, IV; given on cycle day 1].
  • Placebo Comparator: NAC + Neoadjuvant/Adjuvant Placebo
    Neoadjuvant: Prior to surgery, participants receive 4 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1] in combination with platinum doublet NAC, consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1].

Geprüfte Regime

  • Pembrolizumab (KEYTRUDA® / MK-3475 / ):
    200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.
  • Placebo:
    Normal saline by IV infusion Q3W, given on cycle day 1.
  • Cisplatin (PLATINOL®):
    75 mg/m^2 by IV infusion Q3W, given on cycle day 1.
  • Gemcitabine (GEMZAR®):
    1000 mg/m^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC.
  • Pemetrexed (Alimta®):
    500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.

Quelle: ClinicalTrials.gov


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