On November 13, 2020 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that both of its lead clinical programs, SRF617 (targeting CD39) and SRF388 (targeting IL-27), have achieved predefined criteria for advancement into combination and expansion stages of the ongoing Phase 1 trials (Press release, Surface Oncology, NOV 13, 2020, View Source [SID1234570934]). These criteria include safety, successful escalation to a biologically relevant dose, target engagement and meaningful pharmacodynamic activity in the ongoing Phase 1 trials.
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"As we initiated the Phase 1 clinical trials just eight months ago, we are extremely pleased with the progress both of our lead product programs have made to date," said Jeff Goater, chief executive officer. "With the updates announced today, both SRF617 and SRF388 are well-positioned to advance into the key next stages of the ongoing trials in the coming months and ultimately deliver meaningful clinical benefits to patients suffering with cancer."
"We are very encouraged by these data and our clinical progress to date with SRF617 and SRF388," said Rob Ross, M.D., chief medical officer. "Both of these programs are highly innovative, next-generation immunotherapies with the potential to provide novel treatment options to patients with cancer. We look forward to advancing each of these programs into the next stage of the ongoing Phase 1 studies and presenting detailed clinical updates at a medical conference in the first half of 2021."
SRF617 Highlights:
The open label, Phase 1/1b clinical trial of SRF617 was initiated in March 2020 and is enrolling patients with a variety of advanced solid tumors. Summary results from nine patients treated across three dose levels (20 mg, 70 mg and 200 mg intravenously every two weeks) include:
No dose limiting toxicities have been observed and SRF617 has been well-tolerated.
Target occupancy on B cells has increased in a dose-dependent manner, and importantly, within the 200 mg cohort, the goal of meaningful, sustained target occupancy has been achieved. Surface Oncology has already demonstrated that target occupancy is directly correlated with CD39 enzymatic inhibition.
Prolonged stable disease (>5 months) has been seen in one patient with NSCLC who had progressed on prior anti-PD-1 treatment.
While dose escalation will continue because of the lack of dose-limiting toxicities, SRF617 has achieved a dose that supports advancement of the program into the planned combination expansion cohorts (additional details provided below). We anticipate that the combination cohorts will likely begin enrolling in late 2020.
Surface Oncology plans to present detailed initial clinical results from the ongoing Phase 1/1b trial of SRF617 at a medical conference in the first half of 2021.
In May 2020, Surface Oncology announced a clinical collaboration with Merck (NYSE: MRK) to evaluate the safety and efficacy of combining SRF617 with Merck’s KEYTRUDA (pembrolizumab), the first anti-PD-1 therapy approved in the United States. This combination will be studied as a future component of the ongoing first-in-human Phase 1/1b study of SRF617 and will be evaluated in patients with solid tumors, with a focus on patients with gastric cancer and those who have developed resistance to checkpoint inhibition — both areas of high unmet need.
In addition, as part of the clinical development plan, Surface Oncology will initiate SRF617 combinations with gemcitabine and abraxane in patients with pancreatic cancer and SRF617 in combination with AB928, an A2A/A2B small molecule inhibitor, in clinical collaboration with Arcus Biosciences (NYSE: RCUS) in patients with prostate cancer.
SRF388 Highlights:
The open label, Phase 1 clinical trial of the first-in-class antibody SRF388 was initiated in April 2020 and is enrolling patients with a variety of advanced solid tumors. Summary results from nine patients treated across five dose levels (0.003, 0.03, 0.1, 0.3 and 1 mg/kg intravenously every four weeks) include:
No dose limiting toxicities have been observed and SRF388 has been well tolerated.
While dose escalation will continue because of the lack of dose-limiting toxicities, SRF388 has already achieved maximal inhibition of the IL-27 signaling pathway at the 0.3mg/kg dose, as measured in whole blood from patients treated on the trial. Planned monotherapy Phase 2 expansion cohorts in liver cancer and kidney cancer are on track to begin enrolling patients in the first half of 2021.
Prolonged stable disease (>6 months) has been noted in one patient with kidney cancer, who had progressed on prior anti-PD-1 treatment. Notably, kidney cancer is one of the predefined indications of interest for SRF388 based on clear demonstration of pathway activation in clinical samples. No patients with liver cancer have been enrolled in the dose escalation portion of the trial to date.
Surface Oncology plans to present detailed initial clinical results from the ongoing Phase 1 trial of SRF388 at a medical conference in the first half of 2021.
The clinical development plan for SRF388 is based on compelling translational research that indicates that IL-27 is upregulated and functional in both kidney cancer and liver cancer. This work is supported in part by a study presented at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that high levels of IL-27 correlate strongly with the risk of developing liver cancer. The presentation can be found here.
SRF388 recently received Orphan Drug designation and Fast Track designation for the treatment of hepatocellular carcinoma from the FDA.
About SRF617:
SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39, allowing for a dual mechanism of action to promote anti-tumor immunity via reduction of immunosuppressive adenosine in addition to increasing levels of immunostimulatory ATP. A substantial body of research supports a role for CD39 in allowing cancer to evade immune responses. For example, in gastric cancer, immune cells within the tumor often express high levels of CD39, which may impair an overall anti-cancer immune response even in the presence of an anti-PD-1 antibody. In preclinical studies, SRF617 has exhibited strong affinity for and inhibition of CD39, the ability to reduce adenosine and increase ATP levels and anti-tumor activity both as a single agent and in combination with multiple therapeutic agents.
About SRF388:
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver and kidney cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immuno-suppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies and potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping identify patients most likely to respond to SRF388.