This research study is evaluating Lorlatinib in combination with Crizotinib, Binimetinib, or
TNO155 as a possible treatment for either anaplastic lymphoma kinase (ALK)-positive lung
cancer or ROS1-positive lung cancer.
This research study involves four study drugs.
This is a Phase I/II clinical trial of three investigational combinations for treatment of
either anaplastic lymphoma kinase (ALK)-positive or ROS1-positive lung cancer. The three drug
combinations being tested are (1) Lorlatinib combined with Crizotinib and (2) Lorlatinib
combined with Binimetinib and (3) Lorlatinib combined with TNO155.
Lorlatinib is an oral ALK and ROS1 inhibitor. The US Food and Drug Administration (FDA)
has approved Lorlatinib for treatment of ALK-positive lung cancer. The FDA has not
approved Lorlatinib for treatment of ROS1-positive lung cancer.
Crizotinib is an oral ALK and MET inhibitor. The FDA has approved Crizotinib for
treatment of ALK-positive lung cancer. Crizotinib is not approved by the FDA for the
treatment of MET-positive lung cancer. This study will test crizotinib's ability to
block MET signaling. Crizotinib is not approved by the FDA for treatment of
ROS1-positive lung cancer.
Binimetinib is an oral MEK inhibitor. The FDA has not approved binimetinib for treatment
of ALK-positive or ROS1-positive lung cancer but it has been approved for other uses.
TNO155 is an oral SHP2 inhibitor. The FDA has not approved TNO155 for the treatment of
any disease, including ALK-positive or ROS1-positive lung cancer. It is an
The FDA has not approved the combination of Lorlatinib with Binimetinib, Crizotinib, or
TNO155 as a treatment for any disease.
The research study procedures include screening for eligibility and study treatment which
will include evaluations and follow up visits.
Patients will undergo screening and those who fulfill the eligibility criteria will be
assigned to receive either the combination of Lorlatinib and Crizotinib, the combination
of Lorlatinib and Binimetinib, or the combination of Lorlatinib and TNO155. Patients
with ALK-positive or ROS1-positive lung cancer who have extra copies of the MET growth
signal (MET amplification) will be assigned to receive the Lorlatinib and Crizotinib
combination. All other patients will be randomly assigned to receive one of the
This study consists of 2 parts:
The investigators are looking to determine whether combining Lorlatinib with
either Binimetinib, Crizotinib, or TNO155 is well tolerated and to understand
how treatment with the two drugs affects cancer cells and impacts growth
Not everyone who participates in this research study will receive the same
dose of the study drug. The dose given will depend on the number of
participants who have been enrolled in the study prior and how well the dose
The Phase II study will test the safest doses of the combinations (as
established in the Phase I study) in a larger group of patients.
It is expected that about 96 people will take part in this research study
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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