Abstract CT176: A phase 1 open label, first in human trial to study safety and tolerability of NK-T cells combined with vvDD: An accelerated dose escalation in multiple tumor types
Authors: Dorigo Oliver , Contag Pamela Reilly , Moser Justin , Patel Sandip Pravin , Frohlich Mark W. 
Published: June 2022

Abstract
Introduction: BioEclipse Therapeutics has developed CRX100 an adoptive NK-T Cells therapy combined with vaccinia vvDD, an oncolytic virus. vvDD is a Western Reserve (WR) strain vaccinia virus (VACV) that has been further attenuated by the removal of the viral thymidine kinase and growth factor genes, and hence its replication and lytic activity is confined to tumor cells. In preclinical studies in immunocompetent mice the combined therapy eradicated tumor cells and initiated an adaptive immune response.
Trial Design: Our ongoing phase 1 safety clinical trial (IND 19222 at Clinicaltrials.gov) began in January 2021 and includes planned treatment of approximately 24 patients with the potential for 2 doses each. With the dose of ex vivo activated autologous NK-T cells held constant (2-5 X 109), the dose of vvD is increased at 5 dose levels, 3X107, 1x108, 3x108, 1x109 and 3x109 pfu/dose. The first five doses are accelerated in cohorts of one patient and followed by a non-accelerated phase with a cohort of two patients and then 3 cohorts of three patients to determine the MTD, with an additional 8 patients then treated at the MTD. Dose limiting toxicities evaluated by a BOIN design will assist in the dose decision for phase 2.
Inclusion and exclusion criteria: Patients will have tumor progression and have failed standard of care in the indications, triple negative breast cancer, gastric cancer, colorectal carcinoma, hepatocellular carcinoma, ovarian cancer or osteosarcoma.
Results: To date, 4 patients have been treated, including 2 patients with ovarian cancer and 2 with CRC at 4 dose levels. No dose limiting toxicities have been observed. The most common AE is mild fever at 6-12 hours after infusion. Two CRC patients treated at a vvDD dose of 3x107 and 1x109 experienced disease progression. Patient 101-005 with ovarian cancer received two separate infusions 3 months apart each at a dose of 1x108 PFU vvDD combined with 2-5 X 109 ex-vivo activated autologous NKT. Tumor assessment after the first dose showed stable disease (+17.2%) by iRECIST. The CA125 serum biomarker increased temporarily about 3 weeks after infusion. The second ovarian patient (101-007) treated with 3x108 vvDD combined with 2-5 X 109 ex-vivo activated autologous NKT had unconfirmed progression (+21%). There was a slight increase and then a decrease of the CA-125 from 303 to 268. The patient developed new ascites 4 weeks after infusion and required a paracentesis. The ascites did not recur after the paracentesis.
Conclusion: Thus far in escalation, all doses of the therapy have been safe and well-tolerated. Two patients with ovarian cancer treated with the adoptive NKT cell therapy combined with an oncolytic virus demonstrated changes in CA-125 potentially consistent with immune inflammation. Peripheral blood obtained at 3 and 6 month will be analyzed to assess specific immune responses. Dose escalation and enrollment continue for this study.
Citation Format: Oliver Dorigo, Pamela Reilly Contag, Justin Moser, Sandip Pravin Patel, Mark W. Frohlich. A phase 1 open label, first in human trial to study safety and tolerability of NK-T cells combined with vvDD: An accelerated dose escalation in multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT176.