Researchers studied the combination of a cellular vaccine known as HS-110 and nivolumab in an early-phase trial of patients with advanced non–small-cell lung cancer.
The combination of a cellular vaccine known as HS-110 and nivolumab was well tolerated and showed promising efficacy in an early-phase trial of patients with advanced non–small-cell lung cancer (NSCLC).
HS-110, also known as viagenpumatucel-L, is an allogeneic cellular vaccine derived from a human lung adenocarcinoma cell line transfected with the gp96-Ig fusion protein. “To be effective, immune checkpoint blockade requires expansion and intratumoral infiltration of tumor-specific T cells,” said Daniel Morgensztern, MD, of the Siteman Cancer Center at Washington University in St. Louis. Therapeutic cancer vaccines can generate an increase in tumor-specific T cells. “The idea is that the combination of the HS-110 vaccine with the anti–PD-1 antibody nivolumab may result in increased anti-tumor activity compared to nivolumab alone.”
Morgensztern presented results of the phase I/II study at the American Society of Clinical Oncology (ASCO)-Society for Immunotherapy Cancer (SITC) Clinical Immuno-Oncology Symposium, held February 28–March 2 in San Francisco. The phase Ib portion of the trial included 15 patients who were naive to checkpoint inhibitor therapy; the phase II portion, which is ongoing, added 31 checkpoint inhibitor–naive patients (cohort A) and 31 patients who progressed on checkpoint inhibitor therapy (cohort B). All patients had stage IV NSCLC.
The median age in cohort A was 65 years, and 66 years in cohort B. Just over half of both cohorts were female, and more than 80% were white. Most patients had adenocarcinoma, though a few patients in each cohort had squamous cell histology.
In cohort A, the objective response rate (ORR) was 21.4%; there were 9 partial responses, and 12 patients has stable disease (29%), for a disease control rate of 50%. The median overall survival (OS) in cohort A was not yet reached. When divided based on low or high levels of CD8+ tumor-infiltrating lymphocyte counts, the median OS was still not reached, but the 12-month OS rate was 75% in low patients and 50% in high patients. The 12-month OS rate was 44% in PD-L1–negative patients, and 54% in PD-L1–positive patients. The median progression-free survival (PFS) was 2.6 months.
Interestingly, there was a difference in OS based on whether or not the patient experienced an injection site reaction, which suggests an immune response. Those with such reactions had a median OS that wasn’t yet reached, compared with 7.2 months in those who did not, for a hazard ratio of 0.15 (95% CI, 0.05–0.45; P = .0001).
In cohort B, the ORR among 20 evaluable patients was 15%, with 3 partial responses and 8 patients with stable disease (40%), for a disease control rate of 55%. The median PFS was 2.7 months.
Most patients experienced at least one treatment-emergent adverse event (TEAE). In cohort A, 31.8% of patients had a grade 3 or higher TEAE; there were 2 grade 5 TEAEs, including a myocardial infarction and a pulmonary embolism. In cohort B, 22.6% had a grade 3 or higher TEAE.
“In tumors with lower immunogenicity like NSCLC, the question of how to turn on the immune response is an important issue,” said Siwen Hu-Lieskovan, MD, PhD, of the Huntsman Cancer Institute at the University of Utah, who was the discussant for the study. She called this a “novel approach,” and noted that the tumors do seem to transform from “cold,” in immunologic terms, to “hot.” She did note that the two fatal adverse events are concerning, especially in such a small study.
Still, the results are impressive, she said. “Studying the responders would be key to understand the mechanism of response and develop biomarkers to select those patients” that might benefit, she said.