Background: Metastatic neuroendocrine neoplasms (mNEN’s) originating in the gastrointestinal tract are frequently slow growing yet both symptom and disease control remain important. Treatment options include chemoablation, systemic somatostatin analogues (SSA) or peptide receptor radionuclide therapy (PRRT), but additional options are needed.
Methods: This phase 1 study is evaluating the safety, tolerability and response of percutaneous administration of an oncolytic immunotherapy PV-10 in 12 subjects with progressive mNEN with hepatic lesions not amenable to resection or other potentially curative therapy. Target lesion(s) must be 1.0 - 3.9 cm in longest diameter. In Cohort 1 (n = 6) subjects receive PV-10 to a single hepatic lesion per treatment cycle, and can receive PV-10 to additional uninjected hepatic lesions ≥6 weeks after prior injection. Cohort 2 (n = 6) subjects may receive injection of multiple lesions per treatment cycle. The primary endpoint is safety. Secondary endpoints; ORR assessed by contrast enhanced CT and 68Ga-DOTATATE PET, chromogranin A and patient-reported outcome (EORTC QLQ-C30 and GI.NET21).
Results: Cohort 1 has fully enrolled, with 4 of 6 subjects male, median age 65yrs, range 47-72. Primary site: small bowel 3, pancreas 2, caecal 1; grade: Gd1 = 5, Gd2 = 1. All patients received prior SSA and PRRT. Median CgA was 645 (range 30-2819). To date 1 subject has received 4 PV-10 treatment cycles, 1 has received 2 cycles, and 4 have received a single cycle. Toxicity has been acceptable, including pain post procedure, carcinoid flare and nausea. Overall QOL score was stable for 5 of 6 subjects. ORR in injected lesions is 50% (progression in 1 subject), with overall disease control of 84%. CgA response: 5 stable, 1 progression. Additional functional data will be presented.
Conclusions: Hepatic IL PV-10 elicited no safety concerns with encouraging local and systemic disease control. Enrolment to Cohort 2 is continuing.