A Phase 1b Study of Carboplatin and Pemetrexed Plus OMP-21M18 as 1st-line Treatment in Subjects With Non-Squamous Non-Small Cell Lung Cancer
Current cancer therapies often produce an initial reduction in tumour size but may not have
longterm benefits. One possible explanation for this is the presence of cancer cells known
as cancer stem cells. Cancer stem cells represent a small part of the tumour but are
believed to be responsible for much of the growth and spread of the cancer. They may also be
more resistant to traditional therapy, such as chemotherapy and radiation therapy.
The purpose of this study is to test the safety and determine the optimal dose of a new
experimental drug, OMP-21M18, when given in combination with carboplatin and pemetrexed, the
standard of care for patients with nonsquamous nonsmall cell lung cancer (NSCLC). OMP-21M18
is a humanized monoclonal antibody (a protein made in the laboratory) and was developed to
target cancer stem cells. The way the body handles OMP-21M18 will also be investigated.
In this Phase I study, up to 40 participants, 21 years or older, will be enrolled at up to 7
centres in Australia, New Zealand, and Spain. Following informed consent and screening,
participants will receive intravenous infusions of carboplatin and pemetrexed once every 21
days for up to 6 cycles. OMP-21M18 will be administered by intravenous (IV) infusion once
every 21 days (on the same day as the carboplatin and pemetrexed administration).
Participants who complete 6 cycles of carboplatin, pemetrexed, and OMP-21M18 and who have
stable disease or a response may continue to receive OMP-21M18 once every 21 days as
maintenance therapy. After confirming the optimum dose, 14 additional participants will be
treated at the highest dose level that the DSMB considers safe.
Participants will be assessed for disease status every 8 weeks and for safety at every visit
and for 30 days after the end of study drug treatment. Safety will be assessed by adverse
event monitoring, physical examination, vital signs, blood tests, cardiac monitoring, and
participant interview. Response rates, duration of response, time to progression, and
survival will be evaluated, requiring CT or MRI scans and CEA (tumour marker) levels at
baseline and then every 8 weeks. The development of antibodies to treatment will be assessed
throughout the study and up to 12 weeks after the end of study drug treatment. During the
study blood samples will be taken to assess whether OMP-21M18 is producing desired changes
to the genes and proteins related to the cancer (biomarkers).
The study includes an optional part which will investigate how variations in people's
genetic makeup affect their response to medications. This involves the collection of one
blood sample just before participants receive their first dose of study treatment. DNA will
be extracted from the blood sample for testing.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To the determine the maximum tolerated dose of OMP21M18 plus carboplatin and pemetrexed
When each patient in the dose cohort reaches Day 56
United States: Food and Drug Administration