The ALK-positive lung cancer community is always on the lookout for promising new treatments — and this clinical trial at the H. Lee Moffitt Cancer Center fits the bill.
The trial, titled “Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC” (NCT05681780), offers a new approach to fighting oncogene-driven ALK-positive lung cancer using an alternative form of immunotherapy.
Common immunotherapy drugs, like Keytruda, have historically had limited effectiveness in ALK-positive lung cancer. Widely used ALK TKIs, like Lorlatinib and Alectinib, are often very effective, but resistance to treatment nearly always develops.
About the Trial:
According to the listing on ClinicalTrials.gov, this Phase 1 clinical study tests a new generation of Tumor-Infiltrating Lymphocyte (TIL) therapy. TIL therapy uses a patient’s own immune cells, extracted from their tumor, to attack cancer.
What sets this trial apart is the addition of CD40 Ligand (CD40L) to the TILs — a genetic modification designed to make these immune cells more potent in recognizing and destroying cancer cells.
How the Process Works:
· Tumor Harvesting: Patients undergo a surgery (or excisional biopsy) to remove a portion of their tumor, aiming to provide at least 1.5 cm³ of tissue.
· Pre-Treatment: The immunotherapy drug Nivolumab (Opdivo) may be given for up to 6 months before surgery to potentially boost immune cell presence in the tumor.
· TIL Expansion and Enhancement: The TILs are isolated and genetically modified in the lab to express CD40L, boosting their ability to activate the immune system.
· Cell Infusion: After a short course of lymphodepleting chemotherapy to reduce existing immune cells, the enhanced TILs are infused back into the patient, followed by low-dose interleukin-2 (IL-2) to support TIL survival and activity.
· Post-Infusion Nivolumab: Patients will continue receiving nivolumab every 4 weeks for up to 12 months after TIL infusion.
Primary Goals of the Study:
· Assess the safety and feasibility of using CD40L-enhanced TILs.
· Measure the anti-tumor activity in patients with ALK, EGFR, ROS1, or HER2 alterations.
Key Eligibility Criteria:
· Patients with advanced NSCLC driven by ALK, EGFR, ROS1, or HER2 mutations.
· Safely accessible tumor for TIL harvest by surgical resection or excisional biopsy, expected to yield at least 1.5 cm³ of viable tissue.
· Disease progression after standard treatments (including targeted therapies).
· Ability to undergo surgical tumor resection.
Location:
· Moffitt Cancer Center, Tampa, Florida.
Who’s Funding This?
This trial is sponsored by the H. Lee Moffitt Cancer Center and Research Institute, a leading institution in immunotherapy and lung cancer research.
Why this Matters:
This trial offers a new direction: using the patient’s own, enhanced immune cells to overcome resistance and target ALK-driven tumors more effectively.
For ALK-positive patients who have exhausted targeted therapies, CD40L-enhanced TIL therapy represents an exciting and highly personalized immunotherapy approach.
By empowering the immune system with genetically strengthened TILs, researchers hope to achieve deeper, longer-lasting responses. For more information or to see if you might qualify, click here to view the trial listing.
Clinical Trials Currently Recruiting for ALK-positive Cancers.
General Information About Clinical Trials
ALK Positive, along with Wayne State University, is seeking more information about the experiences of those diagnosed with ALK-positive lung cancer. They have created a survey with many points of interest, including the experiences of those who have participated in clinical trials. The survey is confidential and approved by a research governing body. To complete the survey, please click here: ALK-positive Lung Cancer Registry and Survey
As of May 2025, there are at least 40 clinical trials that are recruiting specifically for people with ALK-positive lung cancer. Many of these trials have multiple sites worldwide. Since ALK-positive lung cancer is a rare disease, it is difficult for any one oncologist to be aware of all the trials available. You can advocate for yourself and find a clinical trial that may be a good fit for you at any juncture in treatment.
*The ALK Positive Clinical Trials Spreadsheet was developed by the ALK Positive Medical Committee. The database is updated monthly. Disclaimer: these trials have been consolidated by volunteers and should not be considered exhaustive. Listing of these trials is not an endorsement, and ALK Positive does not recommend one trial over another. Please talk with your doctor about these or any trials you are interested in.
By Ellee Urban with assistance from ChatGPT.
