Innovative Therapeutic Vaccine for ALK+ NSCLC Heads to Phase 1 Clinical Trial
Different types of lung cancer are known to be caused, or driven, by alterations in genes such as EGFR or ALK. One such alteration, the fusion of the ALK gene with another gene (usually EML4), occurs in approximately 5% of patients with non-small cell lung cancer (NSCLC).
Over the past several years, tyrosine kinase inhibitors (TKIs) have been approved to treat advanced ALK-positive lung cancers and may have fewer side effects with improved quality of life for patients. However, as with most TKI treatments, eventually ALK-positive tumors are likely to develop ways to grow, despite treatment, and become resistant to the TKIs.
While immunotherapy, which harnesses the body’s natural ability to fight illness, has been approved for treating many types of cancer, including some types of lung cancer, patients with ALK-positive lung cancer haven’t seen benefits when treated with immunotherapy.
“We needed a different approach to help patients with ALK-positive lung cancer to leverage the power of the body’s natural immune system,” explained Mark Awad, MD, PhD, clinical director of the Lowe Center for Thoracic Oncology Treatment Center at the Dana-Farber Cancer Institute in Boston. “Early work with my collaborator, Dr. Roberto Chiarle at Boston Children’s Hospital, showed that some patients with ALK-positive lung cancer have mild activation of the immune system.”
“This gave us hope to create a vaccine to teach the body’s natural immune system to not just ‘see’ the tumor, but to also attack it,” said Dr. Awad. Using mouse models, the researchers demonstrated that it was possible to use a vaccine to stimulate the natural immune response to fight against ALK-positive tumors.
With a 2018 LUNGevity research grant funded in partnership with ALK Positive, a patient advocacy group dedicated to advancing research and advocating to change the future of ALK-positive lung cancer, Drs. Awad and Chiarle laid the groundwork for a therapeutic vaccine that could improve the survival rates for ALK-positive lung cancer patients.
Similar to a flu shot, the vaccine introduces pieces of the mutated ALK protein into a patient’s body. These protein pieces are carefully selected to prepare the immune system to fight any cells with the mutated ALK protein. The immune cells then circulate through the body looking for and killing any cells that have the mutated ALK protein.
We are hopeful that we’ve translated the laboratory, pre-clinical work into something that will be meaningful for patients.
The research team was awarded a second round of funding from LUNGevity and ALK-Positive in 2020 to conduct a small, phase 1 clinical trial in 20-25 humans to confirm the safety and efficacy of the new vaccine. Because the mutated ALK protein is only found in cancerous cells, the researchers expect that side effects for patients using the therapeutic vaccine will be minimal for patients.
“We’ve approached many big companies who were interested in our data, but based on their other business priorities, they weren’t able to provide support for this research,” explains Dr. Awad. “The support that came from LUNGevity and ALK Positive in 2018 and again in 2020 was really significant in getting the work started and in moving the research forward to be tested in a clinical trial.”
“We will test the vaccine in patients whose ALK-positive NSCLC tumors have developed resistance to previous treatments,” explained Dr. Awad. “If we start with patients whose tumors are growing after previous treatments and then we add the vaccine and see the tumors stop growing or shrink — we’ll know it’s an effective approach.”
“The protocol for the clinical trial is ready and we’re hoping to open the trial this year,” noted Dr. Awad. “This is truly a special situation. And we’re so grateful to be a part of this effort where the people in the lung cancer community—particularly the supporters of LUNGevity and ALK-Positive—have made this completely new type of treatment and this clinical trial possible.”