Table of contents
- Trial overview
- Lung cancer studies
- Lymphoma and other cancers
- What the trials measure
- How the studies are designed
- Safety follow-up and continuation studies
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.[1][3][5] 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.[1][2][6]
Most of the trials are interventional studies, which means the researchers give a treatment and then measure what happens.[1][2] The enrollment sizes vary a lot, from 12 people in one lymphoma study to 3,000 people in a broad tumor-variant study.[4][8]
Lung cancer studies
Several trials focus on non-small cell lung cancer (NSCLC), which is the most common type of lung cancer.[3][6] 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.[6]
Another Phase 2 study, ALBATROS, looks at Lorlatinib after first-line TKI failure in advanced ROS1-positive NSCLC.[5] 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.[5]
A different Phase 2 study examines platinum-pemetrexed chemotherapy plus Lorlatinib in ALK-positive NSCLC with only extracranial disease progression on Lorlatinib.[3] This study compares progression-free survival with older retrospective data, which means past patient records are used as a comparison group.[3]
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.[7]
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.[4] The main outcome was objective response rate, so the study asked how many patients had their lymphoma shrink or disappear during treatment.[4]
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.[2] 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.[2]
What the trials measure
The main endpoints in these studies include objective response rate (ORR), progression-free survival (PFS), disease control, and safety outcomes.[3][4][5][6][8] 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.[5][6]
Safety outcomes include adverse events leading to permanent treatment stop and serious adverse events.[1][8] 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.[2]
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.[2] This is important in studies of targeted cancer treatment because not every helpful treatment causes a fast tumor shrinkage.[2]
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.[1][3][5][6] Some studies are single-arm, meaning everyone gets the same treatment, while others compare Lorlatinib with another drug or with historical data.[3][6]
Participation is usually limited to people with a specific cancer type and a specific molecular feature, such as ALK-positive or ROS1-positive disease.[3][4][5][6] In the broader DRUP study, people are selected because their tumor has a genomic or protein expression variant that may predict drug sensitivity.[2]
Safety follow-up and continuation studies
Two Phase 3 continuation studies focus on safety and tolerability rather than tumor response.[1][8] Their main outcomes are adverse events that lead to permanent discontinuation and all serious adverse events.[1][8]
These continuation studies show that researchers are also interested in what happens when treatment is continued over time in cancer patients.[1][8] In simple terms, they help answer whether the treatment can be kept going safely in the study population.[1][8]
