In short
Clinical trials are investigating Lorlatinib in several cancer settings, especially ALK-positive and ROS1-positive lung cancer and ALK-positive lymphoma. These studies look at safety, efficacy, and how well Lorlatinib works alone or with other treatments in different patient groups.
Key points
- Clinical trials of Lorlatinib are mainly studying cancer, especially ALK-positive and ROS1-positive non-small cell lung cancer. There is also a trial in ALK-positive lymphoma and broader studies in advanced cancers. The data include both Phase 2 and Phase 3 trials, showing that researchers are looking at early activity, safety, and larger comparisons. Main outcomes include objective response rate, progression-free survival, disease control, and serious side effects. Some studies test Lorlatinib alone, while others study it with chemotherapy or in continuation programs. Enrollment ranges from small studies with 12 patients to large studies with 3,000 patients.
Trial overview
The trial data show that Lorlatinib is being studied in several cancer research programs, mainly for people with ALK-positive or ROS1-positive disease. The studies include both Phase 2 and Phase 3 trials, so the research ranges from testing activity and safety to larger comparisons and follow-up studies.
Most of the trials are interventional studies, which means the researchers give a treatment and then measure what happens. The enrollment sizes vary a lot, from 12 people in one lymphoma study to 3,000 people in a broad tumor-variant study.
Lung cancer studies
Several trials focus on non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. One Phase 3 study compares Lorlatinib with crizotinib in people with advanced ALK-positive NSCLC who have not yet received treatment, and its main goal is to see whether Lorlatinib can prolong progression-free survival better than crizotinib.
Another Phase 2 study, ALBATROS, looks at Lorlatinib after first-line TKI failure in advanced ROS1-positive NSCLC. Its main endpoint is objective response rate at 8 weeks, with confirmation needed at 16 weeks, so the team checks how many patients have a confirmed tumor response by scan-based criteria.
A different Phase 2 study examines platinum-pemetrexed chemotherapy plus Lorlatinib in ALK-positive NSCLC with only extracranial disease progression on Lorlatinib. This study compares progression-free survival with older retrospective data, which means past patient records are used as a comparison group.
The ABP study also includes Lorlatinib among several ALK-targeted treatments for locally advanced or metastatic ALK+ NSCLC, and it measures first-line progression-free survival using RECIST v1.1, a standard tumor-measurement system.
Lymphoma and other cancers
One completed Phase 2 trial studied Lorlatinib in people with anaplastic large cells lymphoma (ALCL) ALK+ who had already been treated with ALK inhibitors but no longer responded well. The main outcome was objective response rate, so the study asked how many patients had their lymphoma shrink or disappear during treatment.
Another large Phase 2 trial, the DRUP trial, includes many cancer types such as advanced solid tumors, non-Hodgkin lymphoma, T-cell prolymphocytic leukemia, and multiple myeloma. In that study, Lorviqua is one of many targeted drugs used for patients whose tumor has a molecular or protein expression change that may predict sensitivity to a treatment.
What the trials measure
The main endpoints in these studies include objective response rate (ORR), progression-free survival (PFS), disease control, and safety outcomes. ORR shows the share of patients whose cancer has a confirmed complete or partial response, while PFS measures how long the cancer does not get worse.
Safety outcomes include adverse events leading to permanent treatment stop and serious adverse events. One study also measures how many patients are treated based on their molecular tumor profile, which means treatment is chosen using the tumor’s genetic or protein features.
The DRUP trial also measures stable disease at 16 weeks after treatment starts, which means the cancer has not clearly grown or shrunk but has stayed controlled for a period of time. This is important in studies of targeted cancer treatment because not every helpful treatment causes a fast tumor shrinkage.
How the studies are designed
The trial designs are different, but most are interventional and use Lorlatinib either alone or with other anti-cancer drugs. Some studies are single-arm, meaning everyone gets the same treatment, while others compare Lorlatinib with another drug or with historical data.
Participation is usually limited to people with a specific cancer type and a specific molecular feature, such as ALK-positive or ROS1-positive disease. In the broader DRUP study, people are selected because their tumor has a genomic or protein expression variant that may predict drug sensitivity.
Safety follow-up and continuation studies
Two Phase 3 continuation studies focus on safety and tolerability rather than tumor response. Their main outcomes are adverse events that lead to permanent discontinuation and all serious adverse events.
These continuation studies show that researchers are also interested in what happens when treatment is continued over time in cancer patients. In simple terms, they help answer whether the treatment can be kept going safely in the study population.