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Imfinzi NSCLC
Imfinzi NSCLC
JOURNAL ONKOLOGIE – STUDIE

Efficacy and Safety of Pembrolizumab (MK-3475) With Lenvatinib (E7080/MK-7902) vs. Docetaxel in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) and Progressive Disease (PD) After Platinum Doublet Chemotherapy and Immunotherapy (MK-7902-008/E7080-G000-316/LEAP-008)

Rekrutierend

NCT-Nummer:
NCT03976375

Studienbeginn:
Juni 2019

Letztes Update:
04.06.2021

Wirkstoff:
Pembrolizumab, Lenvatinib, Docetaxel

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
Eisai Inc.

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 140)

Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0501)
69126 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +4962213961304
» Ansprechpartner anzeigen
Mid-Florida Cancer Centers ( Site 1611)
32763 Orange City
United StatesAbgeschlossen» Google-Maps
Billings Clinic ( Site 1631)
59101 Billings
United StatesAbgeschlossen» Google-Maps
Bozeman Health Deaconness Cancer Center ( Site 1632)
59715 Bozeman
United StatesAbgeschlossen» Google-Maps
Kaiser Permanente Center for Health Research-Kaiser Permanente Medical Center ( Site 1644)
97227 Portland
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 503-335-6310
» Ansprechpartner anzeigen
Central Clinical Hospital of the Administration of the President ( Site 0910)
121359 Moscow
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +74955300891
» Ansprechpartner anzeigen
Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site
644013 Omsk
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +73812601037
» Ansprechpartner anzeigen
SPb SBHI City Clinical Oncological Dispensary ( Site 0901)
198255 Saint Petersburg
Russian FederationAbgeschlossen» Google-Maps
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0903)
197758 Saint-Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79117500005
» Ansprechpartner anzeigen
Consorci Hospitalari Mataro ( Site 1008)
08304 Mataro
SpainAbgeschlossen» Google-Maps
Guy s and St Thomas Hospital NHS Foundation Trust ( Site 1102)
SE1 9RT London
United KingdomAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This study will evaluate the efficacy and safety of pembrolizumab (MK-3475) with lenvatinib

(E7080/MK-7902) vs. docetaxel in participants with metastatic non-small cell lung cancer

(NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with

one prior anti-PD-1/PD-L1 monoclonal antibody (mAb). The primary hypotheses of this study are

that pembrolizumab + lenvatinib (compared with docetaxel) prolongs: 1) overall survival (OS);

and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version

1.1 (RECIST 1.1) based on blinded independent central review (BICR).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has a histologically or cytologically confirmed diagnosis of metastatic squamous or

nonsquamous NSCLC (Stage IV: M1a, M1b, M1c).

- Has PD on treatment with one prior anti-PD-1/PD-L1 monoclonal antibody (mAb)

administered either as monotherapy or in combination with other checkpoint inhibitors

or other therapies.

- Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall

course of treatment

- Has PD during/after platinum doublet chemotherapy for metastatic disease.

- Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as

primary therapy.

- Has submitted pre-study imaging that confirmed evidence of PD following initiation of

an anti-PD-1/PD-L1 inhibitor.

- Has at least 1 measurable lesion by computerized tomography (CT) or magnetic resonance

imaging (MRI) per RECIST 1.1, as determined by the local site assessment.

- Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample

(defined as: from initial diagnosis of NSCLC and prior to receiving immunotherapy

[antiPD-1/PD-L1], from the primary lesion or a metastatic lesion).

- Has provided prior to allocation tissue from a newly obtained formalin-fixed sample

from a new biopsy (defined as: after completion of immunotherapy [anti-PD-1/PD-L1] and

before receiving a randomization number), of a tumor lesion not previously irradiated.

- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7

days before the first dose of study intervention but before randomization.

- Has a life expectancy of at least 3 months.

- Male participants receiving pembrolizumab ± lenvatinib or lenvatinib must agree to

refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse;

or 2) follow contraceptive guidance during the treatment period or 7 days after the

last dose of lenvatinib. Male participants receiving docetaxel agree to adhere to the

same conditions during the treatment period and for ≥180 days after the last dose of

study treatment.

- Female participants must be not pregnant, not breastfeeding, and not be a woman of

child-bearing potential (WOCBP). If a WOCBP, agrees to not donate eggs and either use

contraception, or be abstinent from heterosexual intercourse during the treatment

period and for ≥120 days after the last dose of pembrolizumab or 30 days after the

last dose of lenvatinib, whichever occurs first. If a WOCBP receiving docetaxel,

agrees to adhere to the same conditions during the treatment period and for ≥180 days

after the last dose of study treatment.

- Has adequately controlled blood pressure (BP) with or without antihypertensive

medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications

within 1 week before randomization.

- If participant received major surgery or radiation therapy of >30 Gy, they have

recovered from the toxicity and/or complications from the intervention.

- Has adequate organ function.

Exclusion Criteria:

- Has received docetaxel as monotherapy or in combination with other therapies.

- Has received lenvatinib as monotherapy or in combination with an anti-PD-1/PD-L1 mAb.

- Has received: 1) radiotherapy within 2 weeks before the first dose of study treatment;

or 2) lung radiation therapy >30 Gy within 6 months before the first dose of study

treatment.

- Has received a live vaccine within 30 days before the first dose of study treatment.

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

first dose of study treatment.

- Has radiographic evidence of intratumoral cavitation, encasement, or invasion of a

major blood vessel.

- Has clinically significant cardiovascular impairment within 12 months of the first

dose of study treatment.

- Has a history of a gastrointestinal condition or procedure that may affect oral

absorption of study treatment.

- Has a pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.

- Is currently participating in a clinical trial and receiving study therapy or

participated in a study of an investigational agent within 4 weeks of the first dose

of study treatment.

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

or any other form of immunosuppressive therapy within 7 days before the first dose of

study treatment.

- Has a known history of an additional malignancy, except if the participant has

undergone potentially curative therapy with no evidence of disease recurrence for 3

years since initiation of that therapy.

- Has known active central nervous system metastases and/or carcinomatous meningitis.

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

- Has a sensitivity to any of the excipients contained in lenvatinib and/or docetaxel.

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

years.

- Has a history of (noninfectious) pneumonitis that required systemic steroids or

current pneumonitis/interstitial lung disease.

- Has an active infection requiring systemic therapy.

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

- Has a known history of hepatitis B reactive or known active hepatitis C virus

infection.

- Has active tuberculosis.

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

participant's ability to cooperate with the requirements of the study.

- Has a left ventricular ejection fraction (LVEF) below the institutional normal range.

- Has QT interval corrected with Fridericia's formula (QTcF) prolongation to >480 msec.

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

projected duration of the study, starting with the screening visit through at least

120 days after the last dose of pembrolizumab or lenvatinib, or 180 days after the

last dose of docetaxel.

- Has had an allogeneic tissue/solid organ transplant.

Studien-Rationale

Primary outcome:

1. Overall Survival (OS) (Time Frame - Up to ~48 months):
OS is defined as the time from randomization to the date of death due to any cause.

2. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Time Frame - Up to ~36 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. 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. Note: The appearance of one or more new lesions is also considered PD. PFS will be assessed by blinded independent central review (BICR) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Secondary outcome:

1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Docetaxel (Time Frame - Up to ~18 months):
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). ORR will be assessed by BICR per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Lenvatinib Monotherapy (Time Frame - Up to ~36 months):
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions). ORR will be assessed by BICR per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

3. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Time Frame - Up to ~48 months):
DOR is defined as the time from first documented evidence of Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) until disease progression or death due to any cause, whichever occurs first. DOR will be assessed by BICR per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

4. Number of Participants Experiencing an Adverse Event (AE) (Time Frame - Up to ~48 months):
An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.

5. Number of Participants Discontinuing Study Treatment Due to an AE (Time Frame - Up to ~48 months):
The number of participants who discontinue study treatment due to an AE will be presented.

6. Change from Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score (Time Frame - Baseline and Week 12):
The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients, including a combined global health status (GHS)/QoL (Items 29 and 30) scale. For each item, scores range from 0-100, with higher scores indicating higher GHS/QoL. Per protocol, scores for items 29 and 30 will be averaged to compute a combined GHS/QoL scale score. Change from baseline in the combined GHS/QoL scale score will be presented.

7. Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 31) Scale Score (Time Frame - Baseline and Week 12):
Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for cough (Item 31). For this item, individual responses to the question "How much did you cough?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 cough (Item 31) scale score will be presented.

8. Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score (Time Frame - Baseline and Week 12):
Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for chest pain (Item 40). For this item, individual responses to the question "Have you had pain in your chest?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 chest pain (Item 40) scale score will be presented.

9. Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score (Time Frame - Baseline and Week 12):
The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a single-item scale score for dyspnea (Item 8). For this item, individual responses to the question "Were you short of breath?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 dyspnea (Item 8) scale score will be presented.

10. Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score (Time Frame - Baseline and Week 12):
The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a physical functioning (PF) scale (Items 1 to 5). The PF scale consists of participant responses to 5 questions regarding performance of daily activities [1) strenuous activities; 2) long walks; 3) short walks; 4) bed/chair rest; and 5) needing help with eating, dressing, washing themselves or using the toilet]. Overall PF scores range from 0 to 100, with a lower score indicating a better outcome. The change from Baseline in the EORTC QLQ-C30 PF (Items 1 to 5) scale combined score will be presented.

11. Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score (Time Frame - Up to ~48 months):
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a combined GHS/QoL (Items 29 and 30) scale. The TTD in the combined GHS/QoL (Items 29 & 30) scale combined score will be presented, defined as the time to first onset of a ≥10 point decrease from baseline.

12. Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score (Time Frame - Up to ~48 months):
Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for cough (Item 31). The TTD in EORTC QLQ-LC13 cough (Item 31) scale score will be presented, defined as the time to first onset of a ≥10 point decrease from baseline.

13. Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score (Time Frame - Up to ~48 months):
Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for chest pain (Item 40). The TTD in EORTC QLQ-LC13 chest pain (Item 40) scale score will be presented, defined as the time to first onset of a ≥10 point decrease from baseline.

14. Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score (Time Frame - Up to ~48 months):
The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a single-item scale score for dyspnea (Item 8). The TTD in dyspnea (Item 8) scale score will be presented, defined as the time to first onset of a ≥10 point decrease from baseline.

15. Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score (Time Frame - Up to ~48 months):
The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a physical functioning (PF) scale (Items 1 to 5). The TTD in PF (Items 1 to 5) scale combined score will be presented, defined as the time to first onset of a ≥10 point decrease from baseline.

Studien-Arme

  • Experimental: Pembrolizumab+Lenvatinib
    Participants receive pembrolizumab at 200 mg, every 3 weeks (Q3W) via intravenous (IV) infusion on Day 1 of each 21-day cycle, in combination with lenvatinib at 20 mg, once daily (QD) via oral capsule. Pembrolizumab will be administered for up to 35 treatment cycles (~2 years). Lenvantinib will be administered until progressive disease or unacceptable toxicity.
  • Active Comparator: Docetaxel
    Participants receive docetaxel at 75 mg/m^2, Q3W via IV infusion over 1-hour infusion on Day 1 of each 21-day cycle. Docetaxel will be administered until progressive disease or unacceptable toxicity.
  • Experimental: Lenvatinib Monotherapy
    Participants receive lenvatinib at 24 mg, QD via oral capsule. Lenvantinib will be administered until progressive disease or unacceptable toxicity.

Geprüfte Regime

  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    IV infusion of pembrolizumab at 200 mg
  • Lenvatinib (MK-7902 / E7080 / LENVIMA® / ):
    Oral capsules (unit strength: 4 and 10 mg) at 20 mg or 24 mg total daily dose.
  • Docetaxel (TAXOTERE®):
    IV infusion of docetaxel at 75 mg/m^2.

Quelle: ClinicalTrials.gov


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