4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors

Background

Recombinant super-compound interferon (rSIFN-co) is a new class of interferon derived from altering the spatial structure and configuration of the basic interferon protein. rSIFN-co displayed greater anti-tumor activity in solid tumors compared to interferon α-2b in pre-clinical studies.

Methods

Patients with advanced malignancies were enrolled to determine the safety, tolerability, recommended phase II dose (RP2D), pharmacodynamics (PD) and preliminary anti-tumor activities in a 3 + 3 dose escalation design. rSIFN-co was dosed 3 times a week via subcutaneous injection for 21 days followed by 7 days rest. This was preceded by a lead in phase. PD studies comprised of FDG-PET, pre and post treatment changes in plasma cytokine profile and tumor repressive/ enhancing genes as well as 2’5’-oligoadenylate synthetase levels.

Results

39 treatment refractory patients (pts) were enrolled, 18 (46%) colorectal cancer (CRC), 11 (28%) hepatocellular carcinoma (HCC), 6 (15%) non-small cell lung cancer (NSCLC), 2 (5%) melanoma, 1 (3%) renal cell carcinoma (RCC) and 1 (3%) nasopharyngeal carcinoma (NPC). Gender M/F 25/14, median age 61.0 yrs, and ECOG 0/1/2 - 18/20/1. Patients were dosed at 4 dose levels. No dose limiting toxicities were encountered even at DL4 - 30μg (1.6 × 10⁷IU) 3x/week for 21 days followed by 7 days rest. Most common drug related adverse event (drAE) includes pyrexia (92%), chills (54%), fatigue and anorexia (each 41%) and nausea (26%). Grade 3 drAEs include fatigue (8%), WBC decrease (8%), neutropenia (5%), anorexia and pyrexia and weight loss (3%). No grade 4/5 AE were reported. 2 (5.1%) had PR (2 HCC) maintained at 15.9 and 5.9 mths, 19 (48.7%) had disease control (DCR = PR+SD) of which in 6 (31.5%) DCR was >4 mths (3 HCC, 1 NSCLC and 2 CRC), and median PFS was 2.2 mths. Detailed PD data will be presented for all cohorts.

Conclusions

The RP2D of rSIFN-co was 30ug (1.6 × 10⁷IU) 3x/week for 21days followed by 7 days’ rest. Anti-tumour activity seen in heavily pre-treated advanced solid tumor patients. especially in HCC. Future plans involve combinations with other immunotherapies.

Clinical trial identification

NCT02387307.

Editorial acknowledgement

Legal entity responsible for the study

Sichuan Huiyang Life Science and Technology Corporation.

Funding

Sichuan Huiyang Life Science and Technology Corporation.

Disclosure

All authors have declared no conflicts of interest.