Official Title
EA5163/S1709 INSIGNA : A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination With Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) With Immunobiomarker SIGNature-Driven Analysis
Summary:
This phase III trial studies whether pembrolizumab alone as a first-line treatment, followed
by pemetrexed and carboplatin with or without pembrolizumab after disease progression is
superior to induction with pembrolizumab, pemetrexed and carboplatin followed by
pembrolizumab and pemetrexed maintenance in treating patients with stage IV non-squamous
non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumour cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and
carboplatin, work in different ways to stop the growth of tumour cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. It is not yet
known whether giving first-line pembrolizumab followed by pemetrexed and carboplatin with or
without pembrolizumab works better in treating patients with non-squamous non-small cell
cancer.
Trial Description
Primary Outcome:
Secondary Outcome:
- Progression-free survival (PFS)
- Best objective response
- Incidence of adverse events
- PD-L1 positivity
PRIMARY OBJECTIVE:
- To evaluate overall survival (OS) in each of the 2 experimental arms (Arms A and B) to control (Arm C).
SECONDARY OBJECTIVES:
-
To evaluate progression-free survival (PFS) per Response Evaluation
Criteria in Solid Tumours (RECIST) 1.1 for Arm C versus each of Arms A
and B.
- To evaluate best objective response rates per RECIST 1.1 for Arm C versus each of Arms A and B.
- To estimate toxicity within each of the treatment arms via the Common Terminology Criteria for Adverse Events (CTCAE) criteria.
- To compare outcomes between Arms A and B.
- To compare outcomes by treatment arm within subgroups defined by a cutpoint of PD-L1 expression at >= 50%.
BIOMARKER
OBJECTIVE:To collect and bank tissue and blood for future research
studies, including potential development of a prognostic and predictive
signature for MK-3475 (pembrolizumab) in combination with chemotherapy
versus MK-3475 (pembrolizumab) alone.
EXPLORATORY IMAGING OBJECTIVES:
-
To collect and bank standard of care computed tomography (CT) imaging at
baseline and first three follow-up post-treatment scans for developing
the radiomic risk score with the following exploratory objectives:
- Validate
the Radiomic Risk score on pre-treatment scans as well as compute
differences between pre- and post- treatment scans (delta features) in
determining which patients will benefit from first line pembrolizumab in
the metastatic setting in both low (< 50%) and high (> 50%) PD-L1
cohorts using patients in Arm 1 and Arm 2 of the trial where
pembrolizumab is used as first line treatment.
- To use the
Radiomic Risk score in order to predict which patients would benefit
from combination pembrolizumab and subsequent chemotherapy vs.
immunotherapy alone in both low (< 50%) and high (> 50%) PD-L1
cohorts using patients who went on to receive chemotherapy as second
line and stratifying the patients based on those who received benefit
from pembrolizumab plus chemotherapy versus (vs.) pembrolizumab alone.
- Exploratory analysis for other radiomic profiles in predicting response.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM
A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on
day 1. Cycles repeat every 21 days for up to 2 years in the absence of
disease progression or unacceptable toxicity. Within 6 weeks of disease
progression, patients receive pemetrexed IV over 10 minutes and
carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days
for up to 4 cycles in the absence of disease progression or
unacceptable toxicity. Patients then may receive pemetrexed IV over 10
minutes on day 1. Cycles repeat every 21 days in the absence of disease
progression or unacceptable toxicity.
ARM B: Patients receive
pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days
for up to 2 years in the absence of disease progression or unacceptable
toxicity. Within 6 weeks of disease progression, patients receive
pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and
carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days
for up to 4 cycles in the absence of disease progression or
unacceptable toxicity. Patients then receive pembrolizumab IV over 30
minutes and pemetrexed IV over 10 minutes on day 1. Cycles repeat every
21 days for up to 2 years for pembrolizumab in the absence of disease
progression or unacceptable toxicity and until to disease progression
for pemetrexed.
ARM C: Patients receive pembrolizumab IV over 30
minutes, pemetrexed IV over 10 minutes, and carboplatin IV over 30
minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in
the absence of disease progression or unacceptable toxicity. Patients
then receive pembrolizumab IV over 30 minutes and pemetrexed IV over 10
minutes on day 1. Cycles repeat every 21 days for up to 2 years for
pembrolizumab in the absence of disease progression or unacceptable
toxicity and until to disease progression for pemetrexed.
After completion of study treatment, patients are followed up for 5 years.
View this trial on ClinicalTrials.gov
