Ayala Pharmaceuticals Inc (ADXS)

[BarrellofHay]

Stable disease was 7 out of 31 with 1 partial response.

537P - P2 study of ADXS11-001 Immunotherapy in patients with persistent/recurrent, surgically unresectable locoregional, or metastatic squamous cell anal cancer

Background

The number of new anal cancer (SCCA) cases in the US has been rising annually; 20% of patients (pts) will develop metastatic (met) disease, which presents an unmet medical need. A large population-based study showed 88% of SCCA were HPV+ and 73% had HPV-16 (Hoots et al IJC 2009). ADXS11-001 (ADXS) is an irreversibly attenuated Listeria monocytogenes immunotherapy that targets HPV-associated cancers. It is bioengineered to secrete an antigen-adjuvant protein fused to the E7 peptide of HPV-16. It allows the generation of tumor antigen specific cytotoxic T cells that infiltrate and destroy tumor cells. This is the 1st P2 trial to assess the efficacy/safety of ADXS in met SCCA.

Methods

This multicenter, open-label, 2-stage design trial (NCT02399813) includes pts = 18 yrs with histologically confirmed, measurable SCCA and previous = 1?line of therapy for advanced disease. Pts received IV ADXS monotherapy (1x109 colony forming units) every 3 weeks for = 2 years or until a discontinuation criterion was met. Tumor assessments (RECIST 1.1) were every 9 wks. Interim analysis was planned on enrollment of 31 evaluable pts (= 1 post-baseline scan). An objective response rate (ORR) = 10% or a 6-month progression free survival (PFS) = 20% with tolerable safety would allow proceeding to Stage 2.

Results

Preliminary Stage 1 results are reported with data from 29 of the planned 31 evaluable pts. Median age 60 yrs, range 43-77; 27 F/2 M; median follow-up time 191 days. One pt (3.5%) had a durable partial response lasting > 6 months (after progression on prior anti-PD-1 therapy) and 7 pts had stable disease (24%). Disease control rate was 28%. The current KM 6-month PFS estimate is 22%. Common (= 30%) treatment related AEs (TRAEs) were grade 1-2 chills/rigors, fever, hypotension and vomiting. Grade 3 TRAEs of cytokine related syndrome (n?=?1; SAE), infusion related reactions (n?=?2; 1 SAE) and hypotension (n?=?2; 1 SAE) were reported.

Conclusions

ADXS monotherapy showed promising activity and met the predefined 6-month PFS rate. Treatment was well-tolerated with mostly grade 1-2 infusion related AEs that resolved successfully with standard care. Further investigation is ongoing in this population.

Clinical trial identification

NCT02399813