LSAM-PTX Demonstrates Disease Control, Safety in Locally Advanced Pancreatic Cancer

Neil Sharma, MD

Treatment with intratumoral large surface area microparticle paclitaxel (LSAM-PTX; NanoPac) led to disease control and was well tolerated in patients with locally advanced pancreatic cancer, according to interim results from a phase 2 trial (NCT03077685) published in Pancreas.^1,2

Findings showed that evaluable patients treated with LSAM-PTX in the 2-injection cohort experienced a 3-month disease control rate (DCR) of 82% (n = 18/22) and a 6-month DCR of 94% (n = 16/17).1 Notably, the 6-month DCR data did not include 5 patients who had surgery (n = 2), died (n = 1), withdrew (n = 1), and did not have a CT scan (n = 1).²

Additionally, 8 of 22 evaluable patients achieved downstaging from unresectable to resectable disease; among 6 of these patients who underwent surgery, 5 had a R0 resection and 1 had a R1 resection.1 The mean survival for resected patients was 35 months compared with 19 months for unresected patients.

Regarding safety, 84% of treatment-emergent adverse effects (TEAEs) were mild to moderate and considered related to patients’ underlying disease and comorbidities. No patients experienced severe treatment-related AEs or pancreatitis. The most common AEs included abdominal pain and nausea.

“Pancreatic cancer is among the most lethal cancers with 5-year survival of only 12%,” lead study author Neil Sharma, MD, of the Division of Interventional Oncology and Surgical Endoscopy at Parkview Cancer Institute in Fort Wayne, Indiana, stated in a news release. “The interim results from this study, particularly the potential for downstaging and immunomodulation, are encouraging and warrant expanded studies to further evaluate the clinical benefit of neoadjuvant IT LSAM-PTX in combination with standard of care therapy.”

The multicenter, open-label study featured dose-escalation (phase 1) and dose-expansion (phase 2a) cohorts in patients at least 18 years of age with locally advanced pancreatic cancer confirmed by multidisciplinary review.² Patients were required to have target tumors 1.5 cm to 6 cm in diameter. During dose escalation, at least 1 course of prior standard-of-care chemotherapy and hematologic recovery was required; however, in dose expansion, prior chemotherapy was not required, and patients were allowed to initiate chemotherapy after enrollment.

On days patients received injections of LSAM-PTX, tumor measurement and injection volume were determined via endoscopic ultrasound. LSAM-PTX suspensions of 6 mg/mL, 10 mg/mL, or 15 mg/mL were given at up to 20% of tumor volume, up to a maximum of 5 mL. During dose escalation, patients received a single injection of LSAM-PTX. Those in dose expansion were given 2 injections of LSAM-PTX 4 weeks apart at 15 mg/mL, which was determined as the highest-tolerable dose during escalation.

The incidence of TEAEs served as the trial’s primary end point. Secondary end points included overall response rate per RECIST v1.1 criteria, change in pain score, change in tumor markers, and pharmacokinetics.³

Patients enrolled in the dose-expansion portion of the study (n = 25) ranged from 48 years to 96 years of age, and 14 patients were male.2 Twenty patients were White, and all were non-Hispanic/Latino. The median tumor diameter was 3.4 cm (range, 2.2-7.4), the median CA19-9 was 57.5 u/L (range, 2-1198), and the mean time from diagnosis to treatment was 5.5 months (range, 1.5-15.7).

The mean dose of LSAM-PTX during dose expansion was 109.3 mg (range, 33-150).

Pre- and post-treatment tissue samples were available for the 6 patients who underwent resection, which showed that favorable antitumor immunomodulation was observed in the form of increased concentrations of immune effector cells and natural killer cells, along with decreased concentrations of immune suppressor cells.¹

Further data from the study were presented in 2 posters at the 2023 AACR Special Conference on Pancreatic Cancer. The first, presented by Harishankar Gopakumar, MD, of the University of Illinois College of Medicine, showed that among 6 patients who received 2 injections of LSAM-PTX in addition to neoadjuvant chemotherapy at Parkview Health and subsequently underwent surgery, treatment was safe and led to a significant reduction in tumor volume, significant tumor necrosis on a pathology exam, and favorable changes in the immunophenotypic configuration of the tumor microenvironment. Study authors concluded that these preliminary results indicate the addition of neoadjuvant chemotherapy to LSAM-PTX could improve clinical outcomes and increase the rate of downstaging of locally advanced pancreatic cancer to resectable disease.

The second poster, presented by Andrew Hendifar, MD, of Cedars-Sinai Medical Center, centered on data from pre- and post-treatment blood samples from 14 patients who received 4 monthly injections of LSAM-PTX in addition to prior or concurrent chemotherapy. Findings showed that treatment led to peripheral immunomodulation to a phenotype associated with antitumor immune effects, and this was consistent with changes in the tumor microenvironment observed in resected tissue. Additionally, levels of immunosuppressive cell types generally associated with poor clinical outcomes were reduced at 6 months. These data suggested that LSAM-PTX could be amenable to combination with immunotherapy.

References

1. Interim results from a NanOlogy phase 2 clinical trial of its intratumoral investigational drug in the treatment of locally advanced pancreatic cancer. News release. NanOlogy. October 10, 2023. Accessed October 11, 2023. https://nanology.us/2023/10/10/interim-results-from-a-nanology-phase-2-clinical-trial-of-its-intratumoral-investigational-drug-in-the-treatment-of-locally-advanced-pancreatic-cancer/
2. Sharma NR, Lo SK, Hendifar A, et al. Response of locally advanced pancreatic cancer to intratumoral injection of large surface area microparticle paclitaxel: initial report of safety and clinical outcome. Pancreas. Published online October 3, 2023. doi:10.1097/MPA.0000000000002236
3. Trial of NanoPac in subjects with locally advanced pancreatic adenocarcinoma. ClinicalTrials.gov. Updated April 8, 2022. Accessed October 11, 2023. https://clinicaltrials.gov/study/NCT03077685