On September 26, 2023 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing viral immunotherapies to help patients fight cancer, reported updated activity data from its ongoing, open-label, phase 2 clinical trial of CAN-2409 plus valacyclovir in combination with continued immune checkpoint inhibitor (ICI) treatment in 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 (Press release, Candel Therapeutics, SEP 26, 2023, View Source [SID1234635404]). These patients historically have had an expected median overall survival of 10-13 months (Reckamp K et al. J Clin Onc 2022;40:2295-2306). The aim of the CAN-2409 immunotherapy antitumor strategy is to raise the tail on the survival curve by increasing the number of long survivors beyond 10-13 months.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
In 2022, the Company presented data from this phase 2 clinical trial where patients who received two administrations of CAN-2409 plus prodrug demonstrated: 1) increased infiltration of CD8+ cytotoxic T cells in the tumor microenvironment, systemic expansion of effector T cells and increased soluble granzyme B levels in peripheral blood, 2) favorable changes in the trajectory of tumor progression, 3) decreased tumor size of target lesions in most patients, and 4) reduced size of uninjected tumor lesions (Aggarwal C et al. Abstract #9037 ASCO (Free ASCO Whitepaper) June 2022 and Aggarwal C et al. Candel Virtual R&D Day, December 2022). These data were further confirmed in the current update.
Highlights as of August 1, 2023 data cutoff, include:
•
As of data cutoff (August 1, 2023), 40 patients across Cohort 1 (stable disease at enrollment; n=5) and Cohort 2 (progressive disease at enrollment; n=35) were evaluable, as they received two courses of CAN-2409 + valacyclovir and completed the 12-week treatment window.
•
While overall survival is not yet mature, Candel has observed an encouraging number of long survivors, which the Company believes that CAN-2409 may induce a new state of functional immunosurveillance and durable disease control in a subset of the patients.
•
Of the 40 evaluable patients, 15 patients have lived ≥ 12 months; of these, 10 patients have lived > 18 months, of whom 70% (7/10) were alive as of last follow up. All 4 patients (100%) with OS > 24 months were alive at last follow up, with the longest reaching 31.7 months (data cutoff August 1, 2023).
•
An additional 18 out of the 40 evaluable patients are also alive but have not yet reached 12 months of follow up.
•
Notably, many patients treated with CAN-2409 have had long survival (≥ 12 months) despite having disease features generally associated with advanced disease and reduced likelihood to benefit from ICI therapy, such as low or negative PD-L1 expression, including:
•
Amongst patients alive ≥ 12 months with known PD-L1 status (14/15), 93% had negative or low PD-L1 score (<1 or between 1-49).
•
Advanced disease with stage IV in 73% (11/15), lymph node involvement in 73% (11/15), pleural effusion in 40% (6/15), bone metastases in 27% (4/15), adrenal metastases in 20% (3/15), brain metastases in 13% (2/15), liver metastases in 7% (1/15), involvement of 3 or more organs in 13% (2/15), and ECOG performance status 1 in 40% (6/15).
•
There was a significant increase observed in activated central memory, effector-memory, effector T cells, and NK cells after CAN-2409 treatment. These include CD8+Ki67+IFNg+ T cells, CD8+ granzyme B+Ki67+ T cells, CD56+CD16+granzyme B+ NK cells, and gd+ T cells. Candel also observed an increase in B memory cells after CAN-2409 treatment.
•
Candel observed an increase in effector/cytotoxic T cells and NK cells in peripheral blood after the second CAN-2409 administration associated with improved survival (≥ 12 months).
•
Candel continued to observe a favorable safety / tolerability profile after CAN-2409 treatment in NSCLC. There were no dose limiting toxicities or grade 4 or greater treatment related adverse events. Grade 3 treatment related adverse
events were reported in < 10% of patients receiving at least one dose of CAN-2409 (safety population), which Candel believes compares favorably to current standard of care options.
•
Candel expects to share topline overall survival data for Cohort 2 in the second quarter of 2024, assuming mature data at that time.
"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. "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."
Dr. Tak continued, "Our approach is patient-centric. The proposed treatment regimen for CAN-2409 with prodrug is approximately 12 weeks, and patients can continue their anti-PD(L)1 therapy at local treatment centers, reducing treatment burden. The immediate goal is to provide a treatment benefit through disease stabilization via the addition of CAN-2409. The ultimate goal is to extend patient survival with improved quality of life. These data support a survival benefit in individual patients, which continues to be associated with a favorable safety and tolerability profile, particularly when compared to standard of care taxane-based chemotherapy."
"The latest biomarker research performed by Candel, PACT, CIMAC and the National Cancer Institute further supports and expands previous findings," said Francesca Barone, MD, PhD, Chief Scientific Officer of Candel. "We demonstrated for the first time the potential of CAN-2409 to engage the humoral arm of the immune system, broadening the scope of the antitumoral immune response. The correlations between early changes in key effector immune populations after CAN-2409 treatment and survival suggest the possibility to use early biological readouts as predictors of clinical response."
"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. "Most patients progress following ICI treatment and options after progression are often associated with toxicity and small treatment benefit. 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. I look forward to the maturation of these overall survival data and expected readout in Q2 2024."
About CAN-2409
CAN-2409, Candel’s most advanced viral immunotherapy candidate, is an investigational off-the-shelf replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the disease. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. The intra-tumoral administration results in the release of tumor-specific neoantigens in the microenvironment. At the same time, the adenoviral serotype 5 capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This is designed to create the optimal conditions to induce an individualized and specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and ICI have previously been shown in several preclinical and clinical settings. Furthermore, more than 950 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in NSCLC, borderline resectable pancreatic cancer, and localized, non-metastatic prostate cancer in ongoing clinical trials. The U.S. Food and Drug Administration granted Fast Track designation for CAN-2409 plus valacyclovir in combination with pembrolizumab in order 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.