Interim results from a phase 2 trial shows LSAM-PTX may provide therapeutic benefits for patients with locally advanced pancreatic cancer.
Initial safety and clinical outcomes from a phase 2 trial (NCT03077685) showed that treatment with intratumoral (IT) large surface area microparticle paclitaxel (LSAM-PTX; NanoPac) was well-tolerated and improved immune response, improved disease control rate (DCR), restaging leading to surgery, and extended survival in patients with locally advanced pancreatic cancer.1,2
Findings published in Pancreas showed that among the evaluable patients treated with LSAM-PTX in the 2-injection cohort, the DCR at 3 months was 82% (n = 18/22) and at 6 months, the DCR was 94% (n = 16/17). In this cohort, 8 of 22 (36%) patients who were evaluable reached downstaging from unresectable to resectable disease. Six patients underwent surgery, 5 of whom had a R0 resection and 1 who had a R1 resection.1 Further, the mean survival for resected patients increased at 35 months vs 19 months for unresected patients.
Pre- and post-treatment tissue samples were available for the 6 patients who underwent resection. FThis showed that favorable antitumor immunomodulation was seen in the form of increased concentrations of immune effector cells and natural killer cells, as well as with decreased concentrations of immune suppressor cells.1
For safety, most of the treatment-emergent adverse effects (TEAEs; 84%) were mild to moderate and considered related to patients’ underlying disease and comorbidities. Severe treatment-related AEs or pancreatitis were not experienced by any of the patients included in the study, and the most common AEs included abdominal pain and nausea.
“Pancreatic cancer is among the most lethal cancers with 5-year survival of only 12%,” said lead study author Neil Sharma, MD, of the Division of Interventional Oncology and Surgical Endoscopy at Parkview Cancer Institute in Fort Wayne, Indiana, in a press release.1 “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.”
Additional findings from the multicenter, open-label study were presented in 2 posters at the 2023 American Association for Cancer Research (AACR) Special Conference on Pancreatic Cancer. The first was presented by Harishankar Gopakumar, MD, of the University of Illinois College of Medicine, and revealed that in the 6 patients who received 2 injections of LSAM-PTX with neoadjuvant chemotherapy at Parkview Health and subsequently underwent surgery, treatment was safe. Among these patients, the addition of LSAM-PTX to neoadjuvant chemotherapy 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.
According to the study authors, these preliminary results suggest that the addition of neoadjuvant chemotherapy to LSAM-PTX could improve clinical outcomes, as well as increase the rate of downstaging of locally advanced pancreatic cancer to resectable disease.
In a second poster, Andrew Hendifar, MD, of Cedars-Sinai Medical Center, presented data from pre- and post-treatment blood samples collected from 14 patients in the third cohort of the study who received 4 monthly injections of LSAM-PTX plus prior or concurrent chemotherapy. Here, LSAM-PTX led to peripheral immunomodulation to a phenotype associated with antitumor immune effects. These results were 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. Study authors suggest that these data on LSAM-PTX could be amenable to combination with immunotherapy.
The study featured dose-escalation (phase 1) and dose-expansion (phase 2a) cohorts and enrolled patients who were 18 years of age or older with locally advanced pancreatic cancer confirmed by multidisciplinary review.3 Enrollment was open to patients with target tumors 1.5 cm to 6 cm in diameter. In the dose-escalation portion of the study, at least 1 course of prior standard-of-care chemotherapy and hematologic recovery was required, while in the dose-expansion portion, prior chemotherapy was not required. Also, in the dose-expansion cohort, patients were allowed to initiate chemotherapy following enrollment in the study.
In phase 1, 25 patients were included who ranged from 48 years to 96 years of age. Fourteen patients were male, 20 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).
Tumor measurement and injection volume were determined via endoscopic ultrasound on the days patients were given LSAM-PTX. LSAM-PTX suspensions of 6 mg/mL, 10 mg/mL, or 15 mg/mL were administered at up to 20% of tumor volume, up to a maximum of 5 mL.
In the dose-escalation portion, patients were given a single injection of LSAM-PTX, and in the dose-expansion portion, patients received 2 injections of LSAM-PTX 4 weeks apart at 15 mg/mL. This was determined to be the highest-tolerable dose during escalation.
The primary end point of the study was incidence of TEAEs, and secondary end points were overall response rate per RECIST v1.1 criteria, change in pain score, change in tumor markers, and pharmacokinetics.3