Novel Vaccine Shows Association With Survival Based on Smoking History in Patients With Advanced NSCLC

Cesare Gridelli, MD

Vx-001, a cancer vaccine that employs a new strategy targeting a universal tumor antigen, significantly improved overall survival (OS) in patients with advanced or metastatic non—small cell lung cancer (NSCLC) who developed an immune response to the vaccine, according to findings presented at the 2017 ESMO Annual Congress in Madrid, Spain.

Vx-001 also showed activity in patients without natural immunity who were never smokers and patients who smoked for a limited time.

Vx-001 is a peptide-based cancer vaccine against the telomerase reverse transcriptase (TERT) antigen, which is expressed in more than 85% of tumors. The vaccine is composed of 2 nonapeptides and is specific for the approximately 45% of patients that are HLA-A*0201—positive.

Vx-001 did not prolong overall survival (OS) over placebo in the study population; thus, the study did not meet its primary endpoint. Median OS was 14.3 versus 11.1 months, respectively (hazard ratio [HR], 0.97;P= .86).

However, OS was significantly prolonged in the 29% of patients developing a Vx-001 specific immune response post immunization; in these patients the median OS was 21.3 months for immune responders compared with 13.4 months in non-immune responders (P = .004).

“Interestingly, there was a strong correlation between vaccine-induced immune response and clinical outcome,” said Cesare Gridelli, MD, chief of the Division of Medical Oncology, and director of the Department of Oncology/Hematology at S. G. Moscati Hospital in Avelino, Italy.

Gridelli and colleagues tested the Vx-001 vaccine as maintenance therapy in a randomized double-blind phase IIb trial (NCT01935154) in patients with metastatic or advanced NSCLC who did not progress after first-line platinum-based chemotherapy.

Enrollment required patients to be HLA-A*0201—positive with tumors expressing TERT. Of the 1407 subjects screened, 221 were randomized, 101 patients to placebo and 89 to Vx-001, which was administered every 3 months until disease progression. Upon progression, patients received an appropriate second-line treatment.

The primary endpoint was OS, secondary endpoints included time-to-treatment failure (TTF) and OS at 12 months. The exploratory endpoint was the correlations between Vx-001 induced immune and clinical response, and between pre-vaccination natural immunity and clinical outcome.

Natural immunity against several universal tumor antigens was detected at baseline prior to vaccination in 27% of enrolled patients, which suggested that these patients could have strongly immunogenic tumors. However, these patients did not have an OS benefit with Vx-001.

In contrast, analysis of patients without natural immunity at baseline revealed a not statistically significant trend towards improved OS with Vx-001 of 13.2 months versus 8.6 months with placebo (P= .27), suggesting that Vx-001 might be efficient in patients with non-immunogenic tumors.

Vx-001 also showed significantly improved OS in 2 cohorts of patients identified in a subgroup analysis. Never smokers had a median OS of 16.2 months with Vx-001 compared with 8.6 months with placebo (HR, 0.20;P = .0008).

“Since tumor immunogenicity is known to be associated with patients’ smoking status, we conducted a further analysis according to smoking habits. Very interestingly, never smoker patients without natural immunity had a much longer OS with Vx-001; this effect remained strong when we compared former smokers who smoked for a short time,” he said.

In patients who smoked for less than 25 years, median OS was 20.7 months with Vx-001 versus 7.9 months with placebo (HR, 0.29;P = .0007).

Taken in concert, the results suggest that Vx-001 is effective in patients who respond to the vaccine and may also be efficient in patients without natural immunity, particularly in never smokers and patients who smoked for less than 25 years.

Session discussant Jair Bar, MD, PhD, head of the thoracic oncology unit at the Institute of Oncology at Sheba Academic Medical Center in Tel Hashomer, Israel, commented: “This a negative but hypothesis-generating study.”

“The level of immunity to the vaccine could be higher shortly after chemotherapy,” he added, suggesting that further analysis should be done considering the time since the end of therapy and the response to vaccination. He also suggested that Vx-001 be evaluated in combination with immunotherapy or chemotherapy.

Reference:

Gridelli C, Ciuleanu T, Gomez MD, et al. Randomized double blind phase IIb trial in advanced NSCLC patients who did not progress after first line platinum based chemotherapy: Vx-001, a therapeutic cancer vaccine, vs placebo as maintenance therapy. Presented at: 2017 ESMO Annual Congress; Madrid, Spain; September 8-12, 2017.