On May 23, 2024 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported topline overall survival data from its phase 2 clinical trial of CAN-2409, a multimodal biological immunotherapy candidate, plus valacyclovir (prodrug), together with standard of care (SoC) immune checkpoint inhibitor (ICI) therapy in patients with Stage III/IV non-small cell lung cancer (NSCLC) inadequately responding to ICI (anti-PD-(L)1) therapy (Press release, Candel Therapeutics, MAY 23, 2024, View Source [SID1234643583]). The data will be presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held in Chicago, May 31 to June 4, 2024, by Charu Aggarwal, MD, MPH, FASCO, Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the Perelman School of Medicine, University of Pennsylvania and Co-Principal Investigator of the clinical trial.

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Highlights of the presentation include: 1) median overall survival (mOS) of 20.6 months achieved in patients with progressive disease despite ICI treatment after two administrations of CAN-2409 plus prodrug; for context, in a 2022 publication of a clinical trial in a similar patient population, mOS in the control arm that received SoC docetaxel-based chemotherapy was 11.6 months; improved survival was observed across both PD-(L)1 positive and PD-(L)1 negative tumors; 2) beneficial effect on both

injected and uninjected tumors in more than 70% of the patients with metastatic disease and at least one uninjected tumor; and 3) a significant increase in circulating CD8+ cytotoxic and CD4+ effector and central memory T cells and increased soluble granzyme B levels in peripheral blood after the second (‘booster’) injection of CAN-2409, associated with subsequent prolonged survival (in each case, as of an April 1 data cut-off). Together, these data continue to support the emerging differentiated profile of CAN-2409 in this difficult-to-treat condition.

"The results from our phase 2 trial in NSCLC continue to support the tremendous promise of CAN-2409 across multiple solid tumors. We are particularly encouraged by the overall survival observed in the patients whose disease had progressed despite receiving prior anti-PD-(L)1 treatment. Improved overall survival is, ultimately, what matters to patients and to the regulators," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "These results, together with our recently reported overall survival data in a randomized clinical trial in pancreatic cancer, add to the growing body of evidence supporting the notion that CAN-2409 treatment may convert progressive cancer into stable disease associated with survival benefit in advanced cancers with high unmet medical needs."

Previously, the Company received FDA Fast Track Designation for CAN-2409 in NSCLC and pancreatic cancer as well as orphan drug designation in pancreatic cancer.

"Current therapeutic options for advanced NSCLC patients whose disease progresses despite ICI treatment are limited; they are characterized by poor tolerability and limited clinical benefit," said Charu Aggarwal, MD, MPH, FASCO. "The data reported today suggest that CAN-2409 can reactivate these patients’ exhausted immune systems, including those with low PD-(L)1 expression. This systemic anti-tumor immune response translated to a durable response; increased numbers of circulating cytotoxic and memory T cells were associated with subsequent prolonged survival. I look forward to the continued development of CAN-2409 in NSCLC as a promising approach in an area of unmet therapeutic need."

ASCO presentation highlights:

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The open label phase 2 clinical trial evaluated the efficacy and safety of the combination of CAN-2409 plus prodrug (valacyclovir) and continued, unaltered ICI therapy in patients with an inadequate response to ICI after at least 18 weeks of treatment. The objective of the analysis presented at ASCO (Free ASCO Whitepaper) was to explore whether experimental treatment with CAN-2409 plus prodrug could improve mOS in patients treated with two injections.
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46 patients received two administrations of CAN-2409 plus prodrug and were evaluable per protocol.

Cohort 1

Stable Disease at Study Entry

n=5

Cohort 2

Progressive Disease at Study Entry

n=41

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Demographic characteristics of the safety population:
img160460863_1.jpg

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We confirmed previously released data on the ability of CAN-2409 to control disease, with a disease control rate of 100% in cohort 1 and 70% in cohort 2 patients.
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As of April 1, 2024, mOS of 22.0 months was observed across all 46 patients who had an inadequate response to ICI (both cohorts 1 and 2).
In patients with progressive disease despite ICI treatment (cohort 2), a mOS of 20.6 months was observed. A 2022 publication of a clinical trial in a similar patient population reported mOS of 11.6 months for SoC docetaxel-based chemotherapy.1

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Improved mOS was observed in both PD-(L)1 negative and PD-(L)1 positive tumors in patients with progressive disease (n=37 patients in cohort 2 for which PD-(L)1 status at baseline was available).
PD-(L)1 Subgroup

Number of Patients

mOS (months)

Negative (<1%)

16

24.5 (7.0, NA)

Positive (>=1%)

21

20.6 (5.5, NA)

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71.4% of patients with metastatic disease and at least one uninjected tumor (n=35) experienced a beneficial effect on both injected and uninjected tumors, indicating a systemic anti-tumor immune response. When using a threshold of >5% decrease, more than 60.0% of patients showed an abscopal response.

•
Increased numbers of circulating CD8+ cytotoxic and CD4+ effector and central memory T cells as well as elevated levels of soluble granzymes B and H after the second CAN-2409 injection were associated with subsequent prolonged survival, underpinning the systemic immune response elicited by CAN-2409 treatment.

•
Treatment with CAN-2409 in NSCLC continued to exhibit a favorable safety and tolerability profile. Bronchoscopic delivery of CAN-2409 is an extension of
existing care for patients with NSCLC. As of April 1, 2024, there were no dose-limiting toxicities or grade 4 or higher treatment-related adverse events (TRAEs); the majority of TRAEs were grade 1 or 2, and there were three grade 3 TRAEs (one pyrexia, two pneumonitis).

Details on the CAN-2409 ASCO (Free ASCO Whitepaper) abstract are as follows:

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Poster Presentation Title: Overall survival after treatment with CAN-2409 plus valacyclovir in combination with continued ICI in patients with stage III/IV NSCLC with inadequate response to ICI

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Presenter: Charu Aggarwal, MD, MPH, FASCO, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Perelman School of Medicine, University of Pennsylvania

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Session Title: Poster Session – Lung Cancer – Non-Small Cell Metastatic

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Session Date/Time: Monday, June 3, 2024; 1:30 PM – 4:30 PM CT

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Location: Hall A, McCormick Place Convention Center, Chicago, IL

About CAN-2409

CAN-2409, Candel’s most advanced multimodal biological 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 tumor. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. 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 immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. More than 1,000 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 CAN-2409 in NSCLC, borderline resectable PDAC, and localized, non-metastatic prostate cancer in ongoing clinical trials. CAN-2409 plus prodrug (valacyclovir) has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy, and localized primary prostate cancer. Candel’s pivotal phase 3 clinical trial in prostate cancer is being conducted under a Special Protocol Assessment with the FDA. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC.