On April 8, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the presentation of new preclinical and translational data for SRF388, a first-in-class antibody targeting IL-27, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, being held in New Orleans, April 8-13, 2022 (Press release, Surface Oncology, APR 8, 2022, View Source [SID1234611835]). The data will be presented in a poster session, "Determination of a Recommended Phase 2 Dose (RP2D) for SRF388, a First-in-Class IL-27–Blocking Antibody, in Patients with Advanced Solid Tumors" (Abstract #1137) from 9:00 a.m. – 12:30 p.m. CT on Monday, April 11, 2022.

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"We are very pleased to share the compelling preclinical and translational data that enabled us to select the dose for our Phase 2 trials of SRF388," said Alison O’Neill, M.D., chief medical officer. "These data add to the growing body of evidence supporting our belief that IL-27 is a highly immunosuppressive cytokine that serves as a critical regulator of checkpoint protein expression, and treatment with SRF388 shuts down IL-27 signaling. We look forward to providing a clinical update on the program at a scientific conference later in the first half of 2022."

Summary of key SRF388 data:

Pharmacokinetics (PK) from the dose-escalation phase of the SRF388 Phase 1 study were linear, with no dose-limiting toxicities reported.
The concentration of SRF388 associated with optimal antitumor activity in a preclinical mouse model was determined to be approximately 20-fold above the concentration needed for complete inhibition of whole blood phosphorylated STAT1; this concentration of SRF388 was reached and exceeded in patients at a dose of 10 mg/kg.
As previously reported, one patient with squamous non-small-cell lung cancer experienced a confirmed partial response per RECIST v1.1 at this dose.
Changes in the concentration of several serum cytokines and chemokines were observed after SRF388 treatment, including a subset of these biomarkers that correlated with clinical response.
An increase in serum IL-27 levels was observed after SRF388 treatment, a phenomenon described for other anti-cytokine antibodies due to altered clearance of the cytokine-antibody complex.
SRF388 translational data supports the recommended Phase 2 monotherapy dose selection of 10 mg/kg administered intravenously every four weeks, which is being studied in dedicated expansion cohorts of treatment-refractory clear cell renal cell carcinoma (RCC), non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) in the ongoing Phase 1 study (NCT04374877).
The efficacy of adding IL-27 blockade with SRF388 to atezolizumab/bevacizumab in treatment-naïve HCC is also being explored in a placebo-controlled randomized Phase 2 study.
The AACR (Free AACR Whitepaper) e-poster website will be launched on Friday, April 8, 2022, and posters will remain available to registered attendees through Wednesday, July 13, 2022. The SRF388 poster can also be found on Surface Oncology’s website.