Trials Initiated to Evaluate SRF388 Monoclonal Antibody in HCC and NSCLC

Two trials evaluating SRF388, an anti–IL-27 antibody, have been initiated for patients with hepatocellular carcinoma (HCC) and non–small cell lung cancer (NSCLC), according to a press release from Surface Oncology.¹

One is a randomized phase 2 trial of SRF388 in combination with atezolizumab (Tecentriq) and bevacizumab (Avastin) in patients with treatment-naive HCC and the other is a single-arm phase 2 trial of SRF388 as monotherapy in patients with previously treated NSCLC.

“While important progress has been made in recent years, unfortunately the prognosis for the majority of patients with HCC and previously-treated NSCLC remains very poor,” Alison O’Neill, MD, chief medical officer of Surface Oncology, said in a statement. “We have generated strong translational and early clinical data supporting a role for IL-27 blockade in these diseases, and we are pleased to be able to evaluate SRF388’s potential to improve patient outcomes in these indications.”

SRF388 is a fully human monoclonal antibody that inhibits the activity of the immunosuppressive cytokine IL-27. According to analysis of The Cancer Genome Atlas, IL-27p28, EBI3, and IL-27RA transcript levels are frequently elevated in patients with renal cell carcinoma (RCC) and 12 signature genes associated with IL-27 are linked to poor outcomes in RCC.²

Preclinical research indicated that SRF388 could have antitumor activity as a monotherapy, and promotes the activity of anti–PD-1 through increased immune cell activation.¹ In a phase 1 dose escalation trial (NCT04374877) of patients with advanced solid tumors, SRF388 was well tolerated at all doses necessary for maximal inhibition of the IL-27 pathway.³

This trial investigators observed 1 confirmed partial response consisting of 66% tumor shrinkage in a patient with squamous NSCLC who had been refractory to 3 prior lines of therapy, including chemotherapy and PD-1 blockade. There were also 6 patients out of 18 who had stable disease at 8 weeks and 5 with stable disease beyond 16 weeks. The recommended phase 2 dose was determined to be 10 mg/kg and no dose-limiting toxicity was observed.⁴

The trial of SRF388 for patients with HCC is in collaboration with Roche.¹ This blinded, randomized phase 2 trial plans to enroll approximately 100 patients with previously-untreated unresectable or metastatic HCC. Patients will be randomized to receive atezolizumab and bevacizumab plus either SRF388 or a placebo. The primary end point of this study is progression-free survival (PFS) in those who received the combination including SRF388 versus those who received the placebo.

Key secondary end points include safety, overall response rate (ORR), and duration of response (DOR). Final data for this study is expected in the first half of 2024. Interim data is not expected due to the blinded design of the study, but a futility analysis will be performed in early 2023.

The single-arm phase 2 trial of SRF388 for patients with NSCLC will enroll up to 40 patients who have previously received 1 or more lines of systemic therapy. Previous therapy may include PD-1 blockade or therapies that target oncogenic driver mutations. The primary end point for this trial will be ORR according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria. Data from this trial is anticipated in 2023.

SRF388 has received orphan drug designation and a fast track designation for HCC by the FDA.

_References:

_{1. Surface Oncology announces initiation of phase 2 studies evaluating SRF388 in patients with hepatocellular carcinoma and non-small-cell lung cancer. Surface Oncology. Published April 14, 2022. Accessed April 28, 2022. https://bit.ly/3y3h5kr}

_{2. Rausch M, Hua J, Moodley D, et al. Abstract 4550: Increased IL-27 is associated with poor prognosis in renal cell carcinoma and supports use of SRF388, a first-in-class IL-27p28 blocking antibody, to counteract IL-27-mediated immunosuppression in this setting. Cancer Res. 2020;80(16_suppl):4550-4550. doi:10.1158/1538-7445.AM2020-4550}

_{3. Patnaik A, Morgensztern D, Mantia C, et al. Results of a phase 1 study of SRF388, a first-in-human, first-in-class, high-affinity anti-IL-27 antibody in advanced solid tumors. Poster presented at: 2021 American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Chicago, IL. Accessed May 2, 2022. https://bit.ly/3KGeNdn}

_{4. SRF388, a first-in-class IL-27 antibody, demonstrates monotherapy activity in data presented at American Society of Clinical Oncology Annual Meeting. Surface Oncology. Published June 4, 2021. Accessed May 2, 2022. https://bit.ly/3w0VNRN}