A Study of Pembrolizumab Combination Therapy for Advanced Non-Small Cell Lung Cancer
- Conditions
- Treatment of advanced NSCLCMedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-003134-85-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 192
1.Have a histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC] v. 8) NSCLC and study participants should not have had prior systemic therapy for advanced disease.
2. Have confirmation that epidermal growth factor receptor– (EGFR-),anaplastic lymphoma kinase– (ALK-), c-ros oncogene 1 (ROS1), or Bisoform of rapidly accelerated fibrosarcoma (B-Raf) directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR or B-Raf mutations AND absence of ALK or ROS1 gene rearrangements). If participant's tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK and ROS1 translocations will not be required, as this is not part of current diagnostic guidelines.
3. Have measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology. Lesions situated in a previously irradiated area
are considered measurable if progression has been demonstrated in such lesions.
4. Male/female subjects who are at least 18 years of age on the day of
signing the informed consent.
5. A male participant must agree to use a contraceptive as detailed in the protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
6. A female participant is eligible to participate if she is not pregnant,
not breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP)
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in the
protocol during the treatment period and for at least 120 days after the
last dose of study treatment.
7. The participant (or legally acceptable representative if applicable)
provides written informed consent for the study. The participant may
also provide consent for Future Biomedical Research. However, the
participant may participate in the main study without participating in
Future Biomedical Research.
8. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Newly
obtained biopsies are preferred to archival tissue. Repeat samples may
be required if adequate tissue is not provided.
9. Participants must have adequately controlled blood pressure (BP)
with or without antihypertensive medications, defined as BP =150/90
mm Hg at Screening and no change in antihypertensive medications
within 1 week before Cycle 1/Day 1.
10. Have an Eastern Cooperative Oncology Group (ECOG) performance
status of 0 to 1.
11. Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 96
F.1.3 Elderly (>=65 years) yes
1. Has significant cardiovascular impairment within 12 months of the
first dose of study drug: such as history of congestive heart failure
greater than NYHA Class II, unstable angina, myocardial infarction or
cerebrovascular accident (CVA) stroke, cardiac arrhythmia associated
with hemodynamic instability, or a left ventricular ejection fraction
(LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram.
2. Prolongation of QTc interval to >480 ms.
3. Has symptomatic ascites or pleural effusion. A participant who is
clinically stable following treatment for these conditions is eligible.
4. Has had an allogenic tissue/solid organ transplant.
5. A WOCBP who has a positive urine pregnancy test within 72 hours
before the first dose of study treatment.
6. Subjects with proteinuria >1+ on urine dipstick testing will undergo
24-hour urine collection for quantitative assessment of proteinuria.
Subjects with urine protein =1 g/24 h will be ineligible.
7. Subjects who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
8. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any
other condition that might affect the absorption of lenvatinib
9. Radiographic evidence of major blood vessel invasion/infiltration. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage
associated with tumor shrinkage/necrosis following lenvatinib therapy.
10. Clinically significant hemoptysis or tumor bleeding within 2 weeks
prior to the first dose of study drug.
11. Has received prior systemic chemotherapy treatment for
metastatic/recurrent NSCLC.
12. Has current NSCLC disease that can be treated with curative intent
with surgical resection, localized radiotherapy, or chemoradiation.
13. Is expected to require any other form of systemic or localized
antineoplastic therapy while on study.
14. Has received prior therapy with an anti–PD-1, anti–PD-L1, or anti–
PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T cell receptor (eg, CTLA-4, OX 40, CD137).
15. Has received previous treatment with another agent targeting the
LAG3 receptor.
16. Has received previous treatment with another agent targeting VEGF
or the VEGF receptor.
17. Has received prior anticancer therapy including investigational
agents within 4 weeks prior to randomization.
18. Has received prior radiotherapy within 3 weeks of start of study
treatment.
19. Has received a live vaccine within 30 days prior to the first dose of
study treatment.
20. 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 fi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the clinical activity (as assessed by objective response rate [ORR]) of specific pembrolizumab-based combinations.;<br> Secondary Objective: 1) To evaluate the clinical activity (as assessed by progression-free survival [PFS] and overall survival [OS]) of specific pembrolizumab-based combinations. PFS and OS to different specific pembrolizumab-based combinations will be assessed independently in each biomarker-defined group<br> 2) To determine the safety and tolerability of pembrolizumab in combination with either MK- 4280, or lenvatinib. Safety and tolerability to different specific pembrolizumab-based combinations will be assessed independently in each biomarker-defined group<br> ;Primary end point(s): objective response rate (ORR) based on RECIST 1.1 as assessed by local site review;Timepoint(s) of evaluation of this end point: ORR will be used at interim analysis and first database lock
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): 1. PFS based on RECIST 1.1 as assessed by local site review<br> 2. OS<br> 3. Safety as assessed by the number of participants experiencing AEs and the number of participants discontinuing study drug due to AEs.<br> ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be analysed at final database lock