Despite halting the development of SRF388, the developer announces positive phase 1 efficacy and progress in a phase 2 study of SRF388 in combination with pembrolizumab.
In patients with non–small cell lung cancer (NSCLC), treatment with SRF388 monotherapy showed early efficacy, according to results from a phase 1/1b study (NCT04374877) investigating the agent’s use in patients with advanced solid tumors.1
Results from the open-label, first-in-human, dose-escalation, and expansion study of SRF388 show 2 partial responses were achieved in the NSCLC cohort, achieving an objective response rate (ORR) of 100%. Further, there was 1 patient with adenocarcinoma who had durable disease stabilization lasting beyond 56 weeks. The 3 patients evaluated had been previously treated with chemotherapy and anti-PD-L1 agents.
“We are excited by the monotherapy activity seen with SRF388 in relapsed non–small cell lung cancer, an area of high unmet need globally,” said Rob Ross, MD, chief executive officer of Surface Oncology, in a press release. “Two patients with squamous NSCLC have had confirmed partial responses to monotherapy treatment. Both patients had progressed on multiple prior systemic treatments, including anti-PD-L1 antibodies and chemotherapy. In addition, a third patient with highly pretreated NSCLC experienced durable disease stabilization and has remained on study for over a year without progression.”
Promising results from the phase 1 study of SRF388 in advanced solid tumors have led to a phase 2 study of SRF388 in combination with pembrolizumab (Keytruda). According to Surface Oncology, the first patents with late-line NSCLC have been treated and results from the cohort will be announced in the first half of 2023.
The phase 2 study will investigate the efficacy, safety, and tolerability of SRF388 plus pembrolizumab in patients with advanced renal cell carcinoma, hepatocellular carcinoma, or anti-PDL1 relapsed/refractory advanced PD-L1-positive NSCLC.2 The phase 2 coprimary end points of the study are safety/tolerability determined by a summary of treatment-emergent adverse events, and ORR. Secondary end points of the study include ORR, duration of response, disease control rate, progression-free survival, serum concentration of EBI3, anti-drug antibodies to SRF388, and safety/tolerability.
Patients must be 18 years of age or older with locally advanced or metastatic disease. At the time of screening, all patients are required to have a total bilirubin ≤ 1.5 x upper limit of normal (ULN), an ECOG performance status of 0-1, and adequate hematologic function. Patients with HCC must present with Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL, and aspartate/alanine aminotransferase serum glutamic pyruvic transaminase < 2.5 x ULN. Patients with NSCLC are required to have stage IV disease and must have demonstrated progressive disease during or after the most recent treatment regimen.
The study excluded patients who are currently receiving another investigational treatment, previously received an anti-interleukin (IL) 27 antibody or anti-IL 27 targeted therapy, had no prior systemic therapy for unresectable or metastatic disease, received > 5 prior systemic regimens for unresectable or metastatic disease, had prior autologous stem cell transplant ≤ 3 months before the first dose of study treatment, prior allogeneic hematopoietic cell transplant within 6 months of the first dose of study treatment or with a history of or current clinical graft-versus-host disease, or has had an allogenic tissue/solid organ transplant. Patients with unstable or severe uncontrolled medical conditions are also excluded from the study.
Development of SRF388 has been temporarily paused. When development resumes, the study will be recruiting patients with advanced solid tumors who meet the qualifications at trial sites across the United States, and in Korea, and Singapore.