Charu Aggarwal, MD, MPH, Considers Adenoviral Treatment With CAN-2409 in NSCLC With Inadequate Immunotherapy Response

Charu Aggarwal, MD, MPH
Associate Director, Center for Precision Medicine
Physician Leader, Airways Malignancies Research
Leslye M. Heisler Associate Professor for Lung Cancer Excellence
University of Pennsylvania
Philadelphia, PA

First results from a phase 2 study (NCT04495153) of the replication-deficient adenoviral gene construct CAN-2409 in the treatment of patients with stage III and IV non–small cell lung cancer (NSCLC) who had inadequate response to immunotherapy signaled potential efficacy.

Charu Aggarwal, MD, MPH, associate director of the Center for Precision Medicine, physician leader of Airways Malignancies Research, and the Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania in Philadelphia and lead investigator of this study, presented findings from the study at the recent 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. In an interview, she spoke with CancerNetwork^® about CAN-2409 and its potential in this subgroup of patients with NSCLC.

“We are very excited to report the first results for this combination of CAN-2409 with an immunotherapy backbone in patients with NSCLC,” Aggarwal said.

Treatments consisted of intratumoral delivery of CAN-2409 followed by oral valacyclovir (Valtrex) combined with standard anti–PD-1/L1 therapy, with or without chemotherapy. Clinical responses to 2 doses of CAN-2409 were seen in 3 out of 20 RECIST-evaluable patients. Investigators observed tumor size reductions in noninjected lesions, and 2 partial responses (PRs) were ongoing at 6 and 24 weeks, respectively. Investigators concluded that CAN-2409 may be a promising therapy for patients with advanced NSCLC who have inadequate response to frontline immune checkpoint inhibitors with chemotherapy.

CancerNetwork^®: What is the mechanism of action for CAN-2409?

Aggarwal: CAN-2409 is a non-replicative adenovirus delivered through intratumoral injection. The objective [of using this adenovirus] is to create cytotoxicity, which can increase immune-related infiltration and set up a cascade that can improve upon immunotherapy outcomes.

What kind of preliminary antitumor activity was observed with CAN-2409?

This study was conducted in patients with locally-advanced recurrent or metastatic NSCLC who have been treated previously with a first-line immunotherapy backbone regimen [consisting of] either immunotherapy alone or immunotherapy with chemotherapy. [In this study], patients were enrolled in 1 of 3 cohorts. Those in the first cohort had stable disease without any progression following their initial treatment, but hadn’t quite experienced a robust response and we wanted to act upon that stability. Those in the second cohort may have initially responded [to treatment] but had since lost their response, and so [our objective] in these patients was to increase [antitumor] activity off a continuing backbone. And finally, those in the third cohort never responded to immunotherapy. This was our immune-refractory cohort.

[Overall], we’re finding the administration of this gene-mediated cytotoxic immunotherapy in the form of CAN-2409 prolongs stable disease in patients with metastatic and locally-advanced NSCLC. We have preliminary data on patient responses, including two partial responses [PRs].

What did you find regarding the safety profile?

Overall, treatment with CAN-2409 was very well tolerated and safe. Many patients experienced cytokine release syndrome, but those were mostly grade 1 or 2 events. There were no grade 3 or 4 infusion-related reactions.

Where do you see future research efforts going from here?

This is such an important area of unmet need. We must do better for patients who are refractory to immunotherapy. There’s a lot of excitement at ASCO this year over immunotherapy combinations in the second-line setting. That’s where the meat of research will be over the next 5 to 6 years.

What do you hope your colleagues take away from this research?

Our research is exciting because it suggests a possible strategy to build upon patients’ pre-existing immune responses. The beauty of this treatment is that it avoids the necessity of second-line chemotherapy. [With CAN-2409] we’re able to build upon patients’ existing backbone, whether it be maintenance with pembrolizumab [Keytruda] alone or maintenance with pemetrexed [Alimta] and pembrolizumab. We can augment the first-line regimen [with this treatment].

Reference

Aggarwal C, Haas A, Gordon SW, et al. First report of safety/tolerability and preliminary antitumor activity of CAN-2409 in inadequate responders to immune checkpoint inhibitors for stage III/IV NSCLC. J Clin Oncol. 2022;40(16):9037. doi: 10.1200/JCO.2022.40.16_suppl.9037