On December 06, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that new data from the ongoing Phase 1 study of SRF617, an antibody targeting CD39, will be presented in a scientific poster at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO), to be held virtually from December 8-11, 2021 (Press release, Surface Oncology, DEC 6, 2021, View Source [SID1234596482]).

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"Results from this first-in-human dose-escalation study of SRF617 show promising signs of activity, both as a monotherapy and in combination with chemotherapy and pembrolizumab in both immune checkpoint naïve and experienced patients," said Alison O’Neill, M.D., chief medical officer. "We are currently enrolling Phase 2 cohorts for patients with PD-1 naïve gastric cancer and patients with PD-1 relapsed/refractory gastric or non-small-cell lung cancer (NSCLC) and look forward to opening first-line pancreatic cancer cohorts soon."

Safety Overview

The recommended Phase 2 dose for SRF617 monotherapy has been determined to be 1400 mg Q2W based on aggregate review of safety, clinical PK/PD and preclinical data.
No instances of dose-limiting toxicity were observed through dose escalation to the 1400 mg dose level.
Monotherapy Highlights

PK are linear and correlate strongly with PD target occupancy. SRF617 is well-tolerated at doses that sustain full target occupancy throughout the dosing interval and demonstrate dose-dependent loss of CD39 on B cells. Early data from a patient undergoing paired tumor biopsy show marked decrease of CD39 expression in the tumor microenvironment following SRF617 treatment.
Ten of 32 evaluable patients (31%) receiving SRF617 as a monotherapy had disease stabilization at eight weeks, with four (12%) persisting beyond 16 weeks.
One patient with NSCLC whose disease previously progressed on chemotherapy and PD-1 blockade had prolonged disease stabilization beyond 24 weeks.
Combination Highlights

The recommended Phase 2 dose for SRF617 in combination with pembrolizumab has also been determined to be 1400 mg Q2W.
Of patients treated with SRF617 in combination with pembrolizumab (KEYTRUDA), four of eight evaluable patients (50%) had disease stabilization at six weeks, with three of the eight exhibiting disease control at 12 weeks and one beyond 20 weeks.
Of patients treated with SRF617 in combination with gemcitabine/albumin-bound paclitaxel (Abraxane), there was one confirmed partial response in a patient with pancreatic cancer whose disease had progressed on prior chemotherapy. The SRF617 1400mg dose cohort is currently enrolling.
About the SRF617-101 Clinical Trial:

The trial is a Phase 1, open-label, multicenter, first-in-human dose-escalation trial of SRF617, a monoclonal antibody that binds and inhibits CD39 activity, in patients with advanced solid tumors. The monotherapy dose escalation portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of SRF617 as a monotherapy in patients with advanced solid tumors. The combination therapy dose escalation portion of the study evaluates the safety, tolerability, PK and preliminary efficacy of SRF617 in combination with gemcitabine + albumin-bound paclitaxel, or SRF617 in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors.

About SRF617:

SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39 in the tumor microenvironment, 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, pancreatic cancer stromal cells within the tumor micro-environment express high levels of CD39, which may inhibit anti-cancer immune responses. 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. SRF617 has been granted Orphan Drug designation for the treatment of advanced pancreatic cancer by the FDA.