Engineered T-Cell Therapy for Lung Cancer
Trial Summary
What is the purpose of this trial?
This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR) and to see how well they work in treating patients with solid tumor cancers that has spread from where it first started (primary site) to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize KRAS G12V, a protein on the surface of tumor cells. These KRAS G12V-specific T cells may help the body's immune system identify and kill KRAS G12V solid cancer tumor cells.
Do I need to stop my current medications to join the trial?
The trial requires a 'washout' period of at least two weeks from your last systemic treatment, such as immunotherapy or chemotherapy. For small molecules or investigational agents, you need to wait for at least five half-lives. However, there is no washout period for radiation, and bisphosphonates and denosumab are allowed. The protocol does not specify other medications, so you should discuss your current medications with the trial team.
Will I have to stop taking my current medications?
The trial requires that participants stop taking certain medications before starting treatment. You must be at least two weeks from your last systemic treatment, like immunotherapy or chemotherapy, and at least five half-lives from small molecule treatments. However, bisphosphonates and denosumab are allowed.
What data supports the idea that Engineered T-Cell Therapy for Lung Cancer is an effective treatment?
The available research shows that Engineered T-Cell Therapy, specifically targeting KRAS mutations, has shown promise in treating various cancers. For example, T cells engineered to target KRAS mutations have been effective in reducing tumor growth in animal models, as seen in studies involving pancreatic and colorectal cancers. Additionally, T cells engineered to target specific cancer antigens have demonstrated the ability to recognize and attack cancer cells in laboratory settings. These findings suggest that this treatment could be effective for lung cancer as well, given its success in other cancers with similar mutations.12345
What data supports the effectiveness of the treatment for lung cancer?
Research shows that T cells engineered to target KRAS mutations, like the ones used in this treatment, have been effective in recognizing and attacking cancer cells in other types of solid tumors, such as pancreatic and colorectal cancers. These engineered T cells have demonstrated the ability to specifically target and kill tumor cells in laboratory and animal studies, suggesting potential effectiveness in treating lung cancer as well.12345
What safety data is available for engineered T-cell therapy targeting KRASG12V mutations in lung cancer?
The safety data for engineered T-cell therapy targeting KRASG12V mutations is still emerging. Studies have shown that TCR-engineered T cells can effectively target KRASG12V mutations in vitro and in vivo, demonstrating tumor-killing effects. However, challenges such as HLA restriction and the rarity of TILs recognizing mutant KRAS limit the broad application of this therapy. Gene editing techniques like CRISPR-Cas9 are being explored to improve specificity and reduce risks like insertional mutagenesis. While promising, more clinical trials are needed to fully understand the safety profile of this therapy in lung cancer.12467
What safety data exists for engineered T-cell therapy targeting KRASG12V mutations?
The research on engineered T-cell therapy targeting KRASG12V mutations suggests that these treatments have shown promise in preclinical studies for targeting specific cancer mutations, but there is limited information on safety in humans. The studies primarily focus on the effectiveness of these therapies in laboratory and animal models, and do not provide detailed safety data for human participants.12467
Is the treatment FH-A11KRASG12V-TCR a promising treatment for lung cancer?
Yes, FH-A11KRASG12V-TCR is a promising treatment for lung cancer. It uses specially engineered T cells to target and kill cancer cells with a specific mutation called KRASG12V, which is common in many cancers. This approach has shown strong potential in research studies to effectively fight cancer by boosting the body's immune response.12389
How is the FH-A11KRASG12V-TCR treatment different from other lung cancer treatments?
The FH-A11KRASG12V-TCR treatment is unique because it uses engineered T cells that specifically target the KRASG12V mutation, a common driver in many cancers, by using high-affinity T cell receptors (TCRs). This approach allows the immune system to precisely attack cancer cells with this mutation, offering a personalized and potentially more effective treatment option compared to traditional therapies.12389
Research Team
Elena Chiorean
Principal Investigator
Fred Hutch/University of Washington Cancer Consortium
Eligibility Criteria
This trial is for adults with metastatic pancreatic, colorectal, or non-small cell lung cancers that have a specific KRAS G12V mutation. Participants must have tried or declined standard treatments and be in good overall health with proper organ function. They should not be pregnant, breastfeeding, planning to conceive soon, or have uncontrolled illnesses. A commitment to use effective contraception during the study and for 4 months after is required.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Leukapheresis and Lymphodepletion Chemotherapy
Patients undergo leukapheresis and receive lymphodepletion chemotherapy with either cyclophosphamide and fludarabine or bendamustine
Treatment
Patients receive FHA11KRASG12V-TCR IV infusion on day 0, with potential additional infusion as soon as 28 days or up to 1 year after the first infusion
Follow-up
Participants are monitored for safety and effectiveness after treatment
Long-term Follow-up
Participants are monitored long-term for up to 15 years
Treatment Details
Interventions
- Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity KRASG12V Mutation-Specific T Cell Receptors (FH-A11KRASG12V-TCR)
Find a Clinic Near You
Who Is Running the Clinical Trial?
Fred Hutchinson Cancer Center
Lead Sponsor
Affini-T Therapeutics, Inc.
Industry Sponsor