Interim results from a phase 2 clinical trial showed that a novel combination of aldoxorubicin, N-803 (an IL-15 superagonist), and PD-L1 natural killer cell therapy (Nant Cancer Vaccine) plus low-dose chemotherapy doubled overall survival (OS) compared with historical controls in patients with locally advanced or metastatic pancreatic cancer.
The QUILT-88 trial demonstrated a median OS of 6.3 months (95% confidence interval [CI], 5.0-9.8 months) among patients who had progressed after 2 previous lines of therapy, according to Tara Seery, MD, Co-Director, Cellular Therapy Research, and Medical Oncologist, Hoag Cancer Center, Newport Beach, CA, and colleagues, who reported the findings in a poster presentation at the 2022 ASCO Gastrointestinal Cancers Symposium.
When patients with more advanced disease, who had been treated with 4 to 6 previous lines of therapy, were added to the data set (N = 61), the median OS of the entire cohort was 5.8 months (95% CI, 3.9-6.9).
The vaccine was designed to be administered in an outpatient setting, perhaps making it more accessible to future patients than traditional immune checkpoint inhibitors, said Patrick Soon-Shiong, MD, Global Chief Scientific and Medical Officer, ImmunityBio, in a press release.
“Pancreatic cancer claimed an estimated 47,050 lives in the USA in 2020, with an expected 5-year survival of 10%. In patients with advanced disease (>3rd line), the median OS is 3 months. Thus, there is an urgent need for novel treatment options in this disease,” Dr Seery and colleagues noted. “We hypothesize that effective response against pancreatic cancer requires a coordinated approach that orchestrates both the innate and adaptive immune system. We further hypothesize that by orchestrating the activation of the entire immune system, we could accomplish immunogenic cell death with durable responses in this disease.”
The phase 2, open-label QUILT-88 trial evaluated the efficacy and safety of the Nant Cancer Vaccine following low-dose chemoradiation therapy (nab-paclitaxel [Abraxane; 100 mg/m2 intravenously], gemcitabine [Gemzar; 600 mg/m2 intravenously], cyclophosphamide [50 mg orally twice daily]), and low-dose stereotactic body radiation therapy.
The patients’ median age was 62 years, and 62% were male; 93% had metastatic disease. Of the 63 patients enrolled in the trial, 30 (48%) had disease progression after 2 previous lines of therapy. As of data cutoff, patients have been followed for a median of 3.9 months.
At 3 months, 44 patients were evaluable, and in this group, the OS was 81.8% (95% CI, 67.3%-91.8%). Median OS was not yet reached. The median progression-free survival was 2.4 months (95% CI, 2.0-3.7). The disease control rate in 47 evaluable patients was 36.2% (95% CI, 22.7%-51.5%).
To date, 27% of third-line or greater patients (17 of 63) remain on study, with 14 months as the longest duration on therapy at data cutoff.
Treatment-related serious adverse events were uncommon, and no treatment-related deaths were reported. Forty-one (75%) patients experienced grade ≥3 adverse events related to chemotherapy, including anemia in 44%, neutropenia in 24%, and thrombocytopenia in 11%. Five (9%) patients had serious adverse events.
The investigators are independently evaluating 3 cohorts of patients, in the first- and second-line or later maintenance treatment settings, labeled cohorts A, B, and C, respectively. Cohorts A and B have independent experimental and control arms. The study is expected to enroll 328 patients across all 3 cohorts. In cohort C, as reported in the poster, 63 of an expected total of 80 patients have been enrolled, with assessment of OS as the primary objective.
ImmunityBio announced that it plans to meet with the FDA in 2022 to discuss the path for the approval of combination therapies for pancreatic cancer.