Rilvegostomig (AZD2936), a new type of medication that targets both PD-1 and TIGIT proteins, has demonstrated promising results in terms of safety and effectiveness in patients suffering from advanced or metastatic non-small cell lung cancer (NSCLC) with high levels of PD-L1. These patients had previously undergone treatment with at least one checkpoint inhibitor (CPI) but experienced disease progression. The encouraging findings were revealed in the latest data from the phase I/II ARTEMIDE-01 clinical trial (NCT04995523), which was presented at the ASCO 2023 conference.
The initial phase of the ARTEMIDE-01 study aimed to determine the appropriate dosage of rilvegostomig for further investigation in phase 2. This part of the study, referred to as Part A, involved gradually increasing the dose of rilvegostomig. The dosage started at 70 mg with four patients, then escalated to 210 mg with eleven patients, followed by 750 mg with twenty-two patients, and finally 1500 mg with eleven patients.
Based on the results, the recommended Phase II dose (RP2D) of rilvegostomig was determined to be 750 mg. Subsequently, this dosage was carried forward into an expansion cohort called Part B, where an additional 32 patients were enrolled. In both parts of the study, treatment with rilvegostomig was administered every 3 weeks.
Responses were observed across all dose levels.
- At the 750 mg dose of rilvegostomig, the overall response rate (ORR) was determined to be 4.0% and all of the observed responses were classified as partial responses (PR)
- At week 27, the DCR was 22.7% for patients in part A and 3.1% for those in part B
- At week 9, these rates were 45.5% and 40.6%, respectively
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No dose-limiting toxicities were observed during the study, and the maximum-tolerated dose was not reached. The selection of the 750-mg dose was based on modeling analysis and intratumoral receptor occupancy. Flow cytology analyses revealed that doses of rilvegostomig equal to or higher than 210 mg maintained approximately 90% occupancy of PD-1 and TIGIT receptors on peripheral T cells.
During the study, a small percentage of patients (3.8%) discontinued treatment due to adverse events (AEs), with two of these events considered related to rilvegostomig. These treatment-related adverse events (TRAEs) included a Grade 1 case of myocarditis and a Grade 3 case of acute hepatitis.
Among patients receiving the 750-mg dose, 87.0% experienced treatment-emergent AEs (TEAEs), and this percentage was consistent at 87.5% across all doses administered. TRAEs were reported by 51.9% of patients receiving the 750-mg dose and by 46.3% across all doses. Notably, 24.1% of patients receiving rilvegostomig at 750 mg and 27.5% across all doses experienced Grade 3 or greater TEAEs. Additionally, Grade 3 TRAEs were observed in 7.4% of patients in the 750-mg arm and in 5.0% across all doses.
The most common Grade 3 or greater treatment-emergent adverse events (TEAEs) included dyspnea (3.8%), anemia (2.5%), hypercalcemia (2.5%), pleural effusion (2.5%), pneumonia (2.5%), and respiratory failure (2.5%). At the 750-mg dose, the most frequent treatment-related adverse events (TRAEs) were rash, lipase increases, pyrexia, infusion-related reactions, and fatigue, each occurring in less than 10% of patients.
Serious AEs were observed in 24.1% of patients in the 750-mg dose group and in 25.0% across all doses. Of these, 5.6% and 3.8% of patients in the respective groups had serious AEs considered to be related to the treatment. Four deaths occurred due to serious AEs; however, none of these deaths were considered to be related to rilvegostomig.
KOL insights
“The first-in-human ARTEMIDE-01 study provides promising preliminary evidence on the safety and potential efficacy of rilvegostomig, a bispecific antibody targeting PD-1 and TIGIT. Demonstrating a manageable safety profile and signs of antitumor activity in patients with advanced/metastatic NSCLC, who had previously undergone standard therapy including checkpoint inhibitors, this dual immunotherapy approach may offer a new avenue for enhancing T-cell activity and combating immunosuppression in cancer treatment.” –Expert Opinion.
“This dual immunotherapy approach may offer a new avenue for enhancing T-cell activity and combating immunosuppression in cancer treatment.” –Expert Opinion.
Conclusion
The preliminary findings from the ARTEMIDE-01 trial are undeniably promising, as they reveal both the absence of dose-limiting toxicities and encouraging disease control rates at the 27-week mark. These positive results have set the stage for further evaluation of rilvegostomig in patients with advanced non-small cell lung cancer (NSCLC) who have not previously received checkpoint inhibitors.
The ongoing enrollment of participants in the ARTEMIDE-01 study (NCT04995523) will provide additional insights and information regarding the potential of rilvegostomig as a treatment option for advanced NSCLC. Excitingly, AstraZeneca, the pharmaceutical company behind rilvegostomig, has announced plans to initiate a Phase III study, further highlighting their confidence in the agent's therapeutic potential.
In addition to NSCLC, rilvegostomig is also being explored in combinations for the treatment of gastric cancer (NCT05702229) and in other lung cancer settings (NCT04612751), signifying its potential application in a wider range of cancer types. These ongoing investigations underscore the significant interest and commitment to exploring the potential of rilvegostomig as a groundbreaking treatment option for various cancer patients
