Recurrent metastatic cervical cancer ( RMCC ), largely due to infections with high-risk types of human papillomavirus ( HPV ), remains an area of high unmet need for patients progressing after greater than or equal to 1 line of systemic chemotherapy ( sCTx ).
This prospective, P2, 2-stage trial evaluated Axalimogene filolisbac, a Listeria monocytogenes ( Lm ) immunotherapy agent, as a monotherapy in 2nd/3rd line patients with recurrent metastatic cervical cancer.
Co-primary objectives were to assess Axalimogene filolisbac tolerability / safety and frequency of patients who survive for greater than or equal to 12 months after therapy.
Secondary objectives included objective response rate ( ORR ) and overall survival ( OS ). The association between presence / type of high risk HPV and measures of clinical response was explored.
Axalimogene filolisbac is a live, attenuated Lm immunotherapy agent that targets human HPV-transformed cells with an HPV16-E7 fusion protein, stimulates antitumor T-cell immunity and hinders tumor immune tolerance.
Preclinical / clinical evidence has shown that Axalimogene filolisbac is active against multiple high-risk HPV types.
Eligible patients ( greater than or equal to 18 years, measurable disease, GOG Performance Status [ PS ] of 0/1 ) were given IV Axalimogene filolisbac ( 1x109 CFU ) on D1 ( day 1 ) and every 28D for 3 doses in Stage 1 ( S1 ) or until disease progression / 1 year in Stage 2 ( S2 ).
A tissue sample for HPV genotyping was optional.
S1 was completed; S2 was stopped early after a temporary clinical hold on Axalimogene filolisbac and review of available data showed results consistent with S1.
Of 54 patients enrolled, 50 were treated; 12-month overall survival rate was 38%. There was 1 confirmed complete response and 15 patients had a best response of stable disease.
Tissue samples ( n=39 ) were analyzed; 35 were HPV+. Of these, 16 patients were HPV16 family, with 7 ( 44% ) achieving 12-months overall survival; 17 patients were HPV18 family, with 7 ( 41% ) achieving 12-month overall survival.
All patients ( n=50 ) had greater than or equal to 1 adverse event. Treatment-related adverse effects ( TRAEs ) occurred in 96% of patients; 53% had grade 1-2 TRAEs only, 39% had grade 3 TRAEs, and 4% had a possibly related grade 4 TRAE.
The most common TRAEs more than 30% were fatigue, chills, anemia and nausea.
In conclusion, historical 12-month overall survival rates in heavily pretreated pts with recurrent metastatic cervical cancer are less than 30%.
At 1 year 38% of patients were alive after treatment with Axalimogene filolisbac, exceeding the extensive prospective historical data; this is a 52% improvement versus a predicted model-based 12-month overall survival of 25%.
Objective response rate and disease control were seen.
Results in HPV16 patients with recurrent metastatic cervical cancer are consistent with the mechanism of action of Axalimogene filolisbac; similar activity was also seen in HPV18 patients. ( Xagena )
Source: SGO ( Society of Gynecologic Oncology ) Meeting, 2017