Lung cancer is the second most common cancer globally, with non-small cell lung cancer (NSCLC) being the most common lung cancer sub-type, accounting for over 80% of lung cancer diagnoses. While the five-year survival rate for localised lung cancer is around 65%, over 70% of patients are diagnosed with cancer that has spread beyond the lungs, and these patients have a significantly poorer prognosis. Patients with unresectable and/or metastatic disease without an actionable oncogene mutation typically receive immune checkpoint inhibitor (ICI) therapy (anti-PD-1/PD-L1 +/- anti-CTLA-4) and/or chemotherapy. Despite the significant improvement in overall survival in the NSCLC setting with the advent of ICIs, there is still a high level of unmet need, with some patients having primary refractory disease and most patients eventually experiencing disease progression. ICIs with superior response rates, or those that can be utilised in patients with prior checkpoint exposure, are being heavily invested in by both academia and industry. One very promising approach is the development of bispecific ICIs, targeting two checkpoint inhibitor pathways simultaneously such as AstraZeneca’s bispecific anti-PD-1/anti-TIGIT antibody, rilvegostomig.

At the American Society of Clinical Oncology (ASCO) Annual Meeting, 2-6 June 2023, initial findings from the Phase I/II ARTEMIDE-01 study investigating rilvegostomig were presented. Parts A and B of the study enrolled advanced or metastatic NSCLC patients with PD-L1–positive disease, who had progressed on at least one prior ICI therapy. Part A of the study escalated the dose of rilvegostomig from 70mg to 1,500mg, with 750mg identified as the recommended Phase II dose (RP2D). In part B of the study, all patients received RP2D of rilvegostomig at three-weekly intervals. The interim analysis included 80 patients; 72.5% had an adenocarcinoma, and 23.8% had a squamous cell carcinoma while approximately half the patients had PD-L1-low tumours (1%–49%), and the other half had PD-L1-high tumours (≥50%). Almost all patients (96.3%) had metastatic disease, and 22.5% had brain metastases. Patients had received a median of two prior lines of therapy. The median duration of treatment was 11 weeks. Among the 76 evaluable patients, the overall response rate was low at 3.9%, with only partial responses reported. However, 39.5% of patients experienced stable disease, with a nine-week disease control rate of 43.4% and a 27-week disease control rate of 14.5%. Importantly, rilvegostomig was well tolerated with no dose-limiting toxicities reported. Treatment-related adverse events (TRAE) of any grade occurred in 46.3% of patients, with the most common being a rash, lipase increase, pyrexia, infusion-related reactions, and fatigue, each of which occurred in less than 10% of patients. Only 5% of patients had a grade 3 TRAE, and no grade 4–5 TRAEs occurred.

In March 2018, AstraZeneca’s developmental subsidiary MedImmune entered an exclusive licensing agreement with Compugen for the development of bispecific and multi-specific immuno-oncology antibody products in a deal worth up to $225.5m. Rilvegostomig was derived from Compugen’s COM902, a clinical-stage anti-TIGIT antibody. Like COM902, rilvegostomig has a higher affinity for TIGIT compared to its competitors, and a reduced Fc effector function is expected to enhance the anti-tumour immune response. This initial data shows the clinical potential of rilvegostomig, with both efficacy and tolerability demonstrated. However, there is extremely stiff competition in the NSCLC setting, with the pipeline packed with novel ICIs and other therapy classes. The ARTEMIDE-01 study continues to enrol patients, including those who have never been ICI-exposed (Part C and Part D), and AstraZeneca has announced plans for the initiation of a Phase III trial later this year. Rilvegostomig is also being explored in combination with chemotherapy in gastric cancer, and in various combinations in a further Phase I NSCLC trial. GlobalData’s consensus forecast predicts that rilvegostomig will launch in 2027, with global sales reaching $58m by 2029.