To demonstrate superiority with regard to Progression Free Survival based on an Independent Review Committeeassessment of avelumab versus platinum-based doublet in NSCLC subjects with PD-L1+
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival time, defined as the time from date of randomization
until date of the first documentation of PD or
death due to any cause in the absence of documented PD, whichever occurs first
Secondary outcome
- PFS time in PD L1++ ITT subjects,
- Best Overall Response according to RECIST 1.1 and as adjudicated by the IRC,
- Overall Survival time (defined as the time from randomization to the date of
death),
- Changes in Subject-reported Outcomes/Quality of life (assessed by the EQ-5D,
and the EORTC QLQ-C30, and module
QLQ-LC13 questionnaires)
Background summary
Non-small cell lung cancer is the leading cause of cancer-related death in men
and women in the USA and in the EU, resulting in more cancer related deaths
than breast cancer, prostate cancer, and colorectal cancer combined.
In NSCLC, results of standard therapy are poor except for the most localized
cancers where surgery and / or combined modality therapy can provide a cure in
a small percentage of patients. In patients with advanced or metastatic NSCLC,
chemotherapy offers modest benefit, though overall survival (OS) remains poor.
Despite treatment with platinum-based regimens with third generational agents,
patients with metastatic NSCLC have a median survival of approximately 10
months, and a 5-year survival rate of approximately 15%.
Study objective
To demonstrate superiority with regard to Progression Free Survival based on an
Independent Review Committee
assessment of avelumab versus platinum-based doublet in NSCLC subjects with
PD-L1+
Study design
This is a multicenter, international, randomized, open-label, Phase III trial in
chemotherapy-naïve (first line) metastatic/recurrent NSCLC subjects comparing
avelumab to first-line platinum-based chemotherapy. The trial consists of a
28-day screening period, followed by the treatment phase (4 days after
randomization).
Intervention
- Avelumab at a dose of 10 mg/kg as a 1-hour intravenous (IV) infusion once
every 2 weeks until disease progression or unacceptable toxicities, or
- Investigator*s choice platinum-containing chemotherapy regimen to be
administered in
3-week cycles up to a maximum of 6 cycles of IV injection until disease
progression or
unacceptable toxicities.
Study burden and risks
Avelumab is currently being investigated in the following ongoing clinical
studies:
- Trial EMR100070-001 is a Phase I in subjects with metastatic or locally
advanced solid tumors.
- Trial EMR100070-002 is a Phase I in Japanese subjects with metastatic or
locally advanced solid tumors
- Trial EMR100070-003 is a Phase II in subjects with Merkel cell carcinoma
- Trial EMR100070-004 is a Phase III in subjects with non-small cell lung
cancer that has progressed after a platinum-containing doublet.
Overall, the data from those studies support the development of avelumab in
subjects with Stage IV NSCLC who have not yet received systemic treatment for
their metastatic disease.
Based on the nonclinical and Phase I data available to date, the conduct of the
trial is considered justifiable using the dose and dose regimen of the avelumab
as specified in this clinical trial protocol.
The primary known identified risks of exposure to avelumab include
Infusion-related reactions.
In addition, since avelumab has been shown to induce antibody-dependent
cell-mediated cytotoxicity, there is a potential risk of tumor lysis syndrome.
While on trial treatment, subjects will be asked to visit the trial site either
- once every 2 weeks up to Week 13, followed by every 6 weeks thereafter for
subjects randomized to receive avelumab or
- Once every 3 weeks up to Week 13, followed by every 6 weeks thereafter for
subjects randomized to receive chemotherapy.
Frankfurter Strasse 250
Darmstadt 64293
DE
Frankfurter Strasse 250
Darmstadt 64293
DE
Listed location countries
Age
Inclusion criteria
Male or female subjects * 18 years, with an ECOG PS of 0 to 1 at trial entry,
with the availability of a formalinfixed, paraffin-embedded block containing
tumor tissue or 7 (preferably 10) unstained tumor slides with PD-L1+, at least
1 measurable tumor lesion, and with histologically confirmed metastatic or
recurrent NSCLC. Subjects must not have received any treatment for systemic
lung cancer, and have an estimated life expectancy of more than 12 weeks.
Exclusion criteria
Subjects whose disease harbors an activating EGFR mutation, or with
non-squamous cell NSCLC whose disease harbors and anaplastic lymphoma kinase
(ALK) rearrangement are not eligible. Other exclusion criteria include prior
therapy with any antibody or drug targeting T cell coregulatory proteins,
concurrent anticancer treatment, or immunosuppressive agents, known severe
hypersensitivity reactions to monoclonal antibodies (Grade * 3 NCI
CTCAE v 4.03), history of anaphylaxis, or uncontrolled asthma (that is, 3 or
more features of partially controlled asthma), and persisting toxicity related
to prior therapy of Grade > 1 NCI-CTCAE v 4.03. Subjects with brain metastases
are excluded, except those meeting the following criteria: brain metastases
that have been treated locally and are clinically stable for at least 2 weeks
prior to enrollment, subjects must be either off steroids or on a stable or
decreasing dose of <10mg daily prednisone (or equivalent), do not require
steroid maintenance therapy, and do
not have ongoing neurological symptoms that are related to the brain
localization of the disease.
Other protocol defined criteria could apply.
All potential exceptions must be discussed with the study Medical Monitor prior
to enrollment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001537-24-NL |
| Other | IND122898; NCT02576574 |
| CCMO | NL54926.056.15 |