Treatment with CAN-2409 produced promising survival data and continues to show a favorable safety and tolerability profile for the treatment of non-resectable, stage III/IV non–small cell lung cancer.
Encouraging initial survival data was observed with the combination of CAN-2409 plus valacyclovir and continued immune checkpoint inhibitor (ICI) treatment when given to patients with non-resectable, stage III/IV non–small cell lung cancer (NSCLC), who have an inadequate response to front line anti-PD(L)1 therapy, according to updated activity data from a phase 2 clinical trial (NCT04495153).1
Overall survival (OS) data from the study is not yet mature, however, among the 40 evaluable patients included in cohorts 1 and 2 of the study, 15 have lived ≥ 12 months. Ten of the 15 patients have lived > 18 months, and 70% were alive at the last follow-up. Four patients had an OS of > 24 months, and all were alive at last follow-up. The longest OS among these 4 patients reached 31.7 months at the data cutoff date of August 1, 2023. Additionally, 18 out of the 40 evaluable patients are alive, but have not yet reached 12 months of follow-up.
The company expects to share topline OS data for patients enrolled in cohort 2 of the trial in the second quarter of 2024, assuming mature data at that time.
“Although ICIs have transformed initial therapy in NSCLC and extended life for many patients, there still remains a serious unmet need, especially in patients with low levels of PD-L1 expression,” said Charu Aggarwal, MD, MPH, associate professor for lung cancer excellence, Perelman School of Medicine, University of Pennsylvania, and co-principal investigator for the phase 2 clinical trial, in a press release. “Most patients progress following ICI treatment and options after progression are often associated with toxicity and small treatment benefits. The report of today’s initial promising data on survival gives us an insight into the potential of CAN-2409 to produce a sustained anti-tumor immune response and potentially extend the lives of patients living with advanced NSCLC.”
As of the data cutoff date of August 1, 2023, 40 patients were evaluable across cohorts 1 and 2 of the ongoing, open-label, phase 2 trial, and treated with 2 courses of CAN-2409 with valacyclovir. These patients continued until they completed the 12-week treatment window.
Investigators are evaluating the primary end points of response rate and safety of the combination, as well as secondary end points of biomarker studies, OS, progression-free survival, changes in patient-reported outcomes using the NSCLC symptoms assessment questionnaire, and response rate.2
Fourteen of 15 patients were alive ≥ 12 months with known PD-L1 status, and 93% had a negative or low PD-L1 score.1 Eleven of the 15 (73%) patients had advanced disease with stage IV, 11 (73%) had lymph node involvement, 6 (40%) had pleural effusion, 4 (27%) had bone metastases, 3 (20%) had adrenal metastases, 2 (13%) had brain metastases, and 1 (7%) had liver metastases. Further, 2 (13%) patients had involvement of 3 or more organs, and 6 (40%) had an ECOG performance status of 1.
Findings also showed that activated central memory, effector-memory, effector T cells, and NK cells significantly increased after treatment with CAN-2409, including CD8+Ki67+IFNg+ T cells, CD8+ granzyme B+Ki67+ T cells, CD56+CD16+granzyme B+ NK cells, and gd+ T cells. An increase in B memory cells after CAN-2409 treatment was observed, as well as in effector/cytotoxic T cells and NK cells in peripheral blood after the second CAN-2409 administration, which was also linked with improved survival.
A favorable safety and tolerability profile was maintained following CAN-2409 treatment in NSCLC. No dose limiting toxicities or grade 4 or greater treatment-related adverse events (TRAEs) were seen. TRAEs deemed grade 3 were observed in < 10% of patients receiving at least 1 dose of CAN-2409, which compares favorably to standard of care options that are currently available in this space.
“We are very encouraged by the initial survival data, particularly for cohort 2 which enrolled patients whose disease progressed despite receiving anti-PD(L)1 treatment. This patient population represents a major unmet need, since median survival following progression is typically less than 12 months with available treatments,” said Paul Peter Tak, MD, PhD, FMedSci, president and chief executive officer of Candel, in a press release. “Importantly, 93% of patients with long survival were low or negative for PD-L1 expression, which we believe confirms the potential of CAN-2409 to convert patients with highly immunosuppressive tumor microenvironments, unresponsive to ICI treatment, into long term survivors. These early data support the promise and potential of CAN-2409 to provide a long-term survival tail in some of the most difficult to treat NSCLC cases.”
CAN-2409 is an investigational off-the-shelf replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase gene to a patient’s specific tumor and induce an individualized, systemic immune response against the disease. CAN-2409 can potentially treat a broad range of solid tumors. The FDA previously granted fast track designation for CAN-2409 plus valacyclovir in combination with pembrolizumab (Keytruda) to improve survival or delay progression in patients with stage III/IV NSCLC who are resistant to first line anti-PD(L)1 therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy.
In prior preclinical and clinical settings, promising activity was observed with monotherapy and combination regimens of CAN-2409 with standard of care radiotherapy, surgery, chemotherapy, and ICI.
To date, over 950 patients have been given CAN-2409. In addition to NSCLC research, the agent is being evaluated in ongoing trials for patients with borderline resectable pancreatic cancer, and localized, non-metastatic prostate cancer.