SRF388 Monotherapy Generates Responses in Locally Advanced/Metastatic NSCLC

Rob Ross, MD

SRF388, a first-in-class antibody targeting IL-27, elicited responses in pretreated patients with locally advanced or metastatic non–small cell lung cancer (NSCLC), according to data from an ongoing phase 1/1b trial (NCT04374877).¹

Among 9 patients who received SRF388 monotherapy at or above the recommended phase 2 dose (RP2D), 2 patients achieved a confirmed partial response (PR) for an overall response rate (ORR) of 22%. Notably, the confirmed PRs were observed in the only 2 evaluable patients with squamous NSCLC. Additionally, 1 patient with adenocarcinoma experienced durable stable disease that was ongoing for more than 56 weeks as of the August 24, 2022, data cutoff. All 3 patients had received prior treatment with chemotherapy and anti–PD-(L)1 agents.

Detailed clinical results from ongoing studies of SRF388 are expected to be shared in the first half of 2023.

“We are excited by the monotherapy activity seen with SRF388 in relapsed NSCLC, an area of high unmet need globally,” Rob Ross, MD, chief executive officer of Surface Oncology, stated in a press release. “Based on these promising results in relapsed NSCLC, we have opened the second stage of our trial investigating SRF388 as a monotherapy, and we have treated our first patients in a new cohort to investigate SRF388 in combination with pembrolizumab in second- to fourth-line NSCLC.”

SRF388 is a fully human anti–IL-27 antibody designed to inhibit the activity of the immunosuppressive cytokine.² IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors in patients with liver, kidney, and lung cancer.

Preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, leading to immune cell activation in combination with other cancer therapies, including anti–PD-1 therapy, and potent antitumor effects as a monotherapy.

Part B of the phase 1 trial is evaluating SRF388 monotherapy at the RP2D in up to 40 patients with NSCLC and up to 40 patients with hepatocellular carcinoma (HCC).³ Notably, the trial also planned to enroll up to 40 patients with renal cell carcinoma (RCC); however, Surface Oncology announced that it has stopped enrollment for the RCC cohort to focus efforts on NSCLC and HCC, based on encouraging data in those patients.

Patients with NSCLC are required to have histologically confirmed locally advanced or metastatic stage IV disease that has progressed during or after standard therapy, and for whom no available therapies are appropriate. Other key inclusion criteria include at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate hematologic function.

Key exclusion criteria include previous treatment with an anti–IL-27 antibody or anti–IL-27 targeted therapy, a history of grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs, major surgery within 4 weeks prior to screening, or an unstable or severe uncontrolled medical condition.

ORR is serving as the primary end point of part B of the study. Secondary end points include duration of response, disease control rate, progression-free survival, pharmacokinetics, pharmacodynamics, and safety.

SRF388 will also be evaluated in combination with pembrolizumab (Keytruda) in patients with NSCLC who have progressed after 1 to 3 prior lines of therapy, including chemotherapy and anti–PD-1 agents. The study is anticipated to enroll up to 40 patients with NSCLC.

References

1. Surface Oncology announces promising SRF388 monotherapy data in non-small cell lung cancer (NSCLC), opening second stage of monotherapy trial and NSCLC pembrolizumab combination cohort. News release. Surface Oncology. November 2, 2022. Accessed November 3, 2022. http://bit.ly/3zHnPo5
2. Surface Oncology announces initiation of phase 2 studies evaluating SRF388 in patients with hepatocellular carcinoma and non-small-cell lung cancer. News release. Surface Oncology. April 14, 2022. Accessed November 3, 2022. http://bit.ly/3SVKsvK
3. Study of SRF388 in patients with advanced solid tumors. ClinicalTrials.gov. Updated August 18, 2022. Accessed November 3, 2022. https://clinicaltrials.gov/ct2/show/NCT04374877