Rilvegostomig Shows Durable Responses in Checkpoint Inhibitor-Resistant NSCLC: ARTEMIDE-01 Phase I/II Results
核心洞察
Rilvegostomig, a bispecific antibody targeting PD-1 (搜索) and TIGIT (搜索), produced a 5.6% objective response rate at the recommended Phase II dose of 750 mg every 3 weeks in checkpoint inhibitor-resistant NSCLC.
The first-in-human ARTEMIDE-01 trial reported a 6-month disease control rate of 31.5% and median progression-free survival of 3.8 months, with several durable responses lasting at least six months.
No dose-limiting toxicities were observed and the maximum tolerated dose was not reached, with Grade 3 treatment-related adverse events occurring in only 8.4% of patients.
A first-in-human study of rilvegostomig, a bispecific antibody designed to simultaneously target PD-1 (搜索) and TIGIT (搜索), has reported preliminary antitumor activity with a manageable safety profile in patients with previously treated, checkpoint inhibitor-resistant advanced or metastatic non-small-cell lung cancer (搜索) (NSCLC). Results from the Phase I/II ARTEMIDE-01 trial, published in Clinical Cancer Research, showed that rilvegostomig at the recommended Phase II dose of 750 mg every 3 weeks produced an objective response rate of 5.6%, a 6-month disease control rate of 31.5%, and a median progression-free survival of 3.8 months.
Importantly, the study involved a difficult-to-treat population. All patients had previously received PD-(L)1 inhibitor therapy, nearly all had received platinum-based chemotherapy, and participants had documented primary or secondary resistance to their previous checkpoint inhibitor regimen (Rohrberg et al., 2026). The findings provide an early clinical test of whether two inhibitory immune pathways, PD-1 (搜索) and TIGIT (搜索), can be targeted within a single bispecific antibody after resistance to conventional checkpoint inhibition has developed.
What Is Rilvegostomig?
Rilvegostomig is an Fc-reduced, monovalent, bispecific humanized IgG1 antibody targeting both PD-1 (搜索) and TIGIT (搜索). PD-1 is an established immune checkpoint and the target of several widely used immunotherapies. TIGIT, or T-cell immunoreceptor with Ig and ITIM domains, is another coinhibitory receptor expressed on activated T cells and natural killer cells. Both pathways can suppress antitumor immune responses, and rilvegostomig is designed to block the two receptors simultaneously within a single antibody construct (Rohrberg et al., 2026).
The drug was built using the DuetMab antibody platform and incorporates reduced Fc activity. According to the investigators, the bispecific structure is intended to provide coordinated inhibition of PD-1 (搜索) and TIGIT (搜索) while its Fc-reduced configuration limits depletion of immune effector cells expressing the targeted receptors. Preclinical work cited in the study showed that rilvegostomig enhanced CD8-positive T-cell activation in patient-derived NSCLC tumor models compared with either individual checkpoint blockade or co-administration of separate PD-1- and TIGIT-targeting antibodies (Rohrberg et al., 2026).
Why Target PD-1 and TIGIT Together?
Checkpoint inhibitors targeting PD-1 (搜索) or PD-L1 have become an important part of treatment for metastatic NSCLC without actionable oncogenic driver alterations. However, not every patient responds, and disease progression eventually occurs in many patients who initially benefit. Treatment options after progression following checkpoint inhibitor-based therapy remain limited, creating interest in strategies capable of overcoming or bypassing immune resistance (Rohrberg et al., 2026).
The biological rationale for combined blockade is that PD-1 (搜索) and TIGIT (搜索) can independently contribute to suppression of antitumor T-cell function. Simultaneously targeting both receptors could therefore produce a broader immune effect than inhibiting only one pathway. Rather than administering separate antibodies, rilvegostomig brings both functions into one molecule. ARTEMIDE-01 was designed to determine whether that concept could be translated into acceptable safety, pharmacodynamic target engagement, and preliminary clinical activity in patients whose tumors had already demonstrated resistance to checkpoint inhibitor therapy.
Trial Design and Patient Population
ARTEMIDE-01 (NCT04995523) is a multicenter, open-label Phase I/II trial evaluating rilvegostomig monotherapy. The analysis reported by Rohrberg and colleagues included Parts A and B, which enrolled checkpoint inhibitor-experienced patients with PD-L1-positive advanced or metastatic NSCLC. Part A was the dose-escalation component and enrolled 51 patients, who received intravenous rilvegostomig at 70 mg, 210 mg, 750 mg, or 1,500 mg every 3 weeks. Part B was the dose-expansion component and enrolled an additional 32 patients after the recommended Phase II dose had been determined. Overall, 83 patients were treated across Parts A and B (Rohrberg et al., 2026).
Eligible patients had unresectable stage III or stage IV squamous or nonsquamous NSCLC, ECOG performance status 0 or 1, measurable disease according to RECIST 1.1, and tumor PD-L1 expression with a tumor proportion score of at least 1%. Patients also had to have received previous checkpoint inhibitor and platinum-based chemotherapy and to have demonstrated primary or secondary resistance to their previous checkpoint inhibitor regimen. Patients with sensitizing EGFR mutations, ALK fusions, or other genomic alterations for which an approved first-line targeted therapy was available were excluded, as were patients with previous anti-TIGIT (搜索) therapy (Rohrberg et al., 2026).
Between September 2021 and March 2023, 83 patients were treated at 15 sites across seven countries. The median age was 63 years, and 47.0% of participants were aged 65 years or older. Histologically, 72.3% had adenocarcinoma and 22.9% had squamous cell carcinoma. Nearly half of the population, 47.0%, had a locally reported PD-L1 tumor proportion score of at least 50%. All patients had previously received a PD-(L)1 inhibitor, while 96.4% had received platinum-based chemotherapy. The median number of previous cancer-treatment lines was two. Resistance to prior checkpoint inhibition was categorized as 37.3% primary resistance and 62.7% secondary resistance (Rohrberg et al., 2026).
Dose Selection: 750 mg Every 3 Weeks
No dose-limiting toxicities were observed during dose escalation, and the maximum tolerated dose was not reached. Instead of selecting the recommended Phase II dose solely on the basis of toxicity, investigators integrated safety, pharmacokinetic, pharmacodynamic, antitumor activity, and receptor-occupancy data. Rilvegostomig produced sustained ≥90% PD-1 (搜索) and TIGIT (搜索) receptor occupancy in peripheral CD4-positive and CD8-positive T cells at doses of at least 210 mg every 3 weeks. Pharmacodynamic modeling further indicated that 750 mg every 3 weeks was the lowest tested dose predicted to achieve ≥90% intratumoral occupancy of both PD-1 and TIGIT. Based on the combined evidence, 750 mg every 3 weeks was selected as the recommended Phase II dose (Rohrberg et al., 2026).
Antitumor Activity and Durable Responses
Clinical activity was modest at the population level but included several durable responses. At the recommended Phase II dose of 750 mg every 3 weeks, the objective response rate was 5.6% (95% CI, 1.2–15.4). The 6-month disease control rate was 31.5% (95% CI, 19.5–45.6), and median progression-free survival was 3.8 months (95% CI, 2.0–4.2). The estimated 12-month progression-free survival rate was 11.9% (95% CI, 4.9–22.2). Across all 83 patients treated at any dose, five patients achieved confirmed partial responses, corresponding to an overall objective response rate of 6.0%. No complete responses were reported (Rohrberg et al., 2026).
The relatively low overall response rate does not fully describe the response pattern observed. Across the overall study population, median duration of response was 14.5 months, and at the recommended Phase II dose, median duration of response was 10.3 months. Four patients had confirmed responses lasting at least six months, with individual duration of response/progression-free survival values of 9.0/25.3 months, 14.5/16.4 months, 32.2/36.1 months, and 10.3/12.4 months. All four durable responders had tumors with PD-L1 TPS ≥50%. Three of the four had adenocarcinoma and one had squamous NSCLC; three had secondary resistance to previous checkpoint inhibition, while one had primary resistance (Rohrberg et al., 2026).
Safety Profile
Across all 83 patients, 90.4% experienced a treatment-emergent adverse event of any grade. Treatment-related adverse events occurred in 54.2% of patients, and Grade 3 treatment-related adverse events occurred in 8.4%. Importantly, no Grade 4 or Grade 5 treatment-related adverse events were reported. The most common treatment-related adverse events were rash (8.4%), pruritus (7.2%), infusion-related reaction (6.0%), and increased lipase (6.0%). Individual Grade 3 treatment-related events included acute hepatitis, increased ALT, increased AST, colitis, diarrhea, fatigue, an immune-system disorder, infusion-related reaction, pneumonitis, and rash, each occurring in one patient (Rohrberg et al., 2026).
Investigator-assessed immune-mediated adverse events occurred in 18.1% of patients, with Grade 3 immune-mediated events in 4.8% and no Grade 4 or 5 immune-mediated events reported. Reported immune-mediated events occurring in more than one patient included pruritus, infusion-related reactions, maculopapular rash, and pneumonitis. Systemic corticosteroids were used to manage immune-mediated adverse events in 7.2% of patients. Treatment-related serious adverse events occurred in 7.2%. Two patients (2.4%) discontinued rilvegostomig because of treatment-related adverse events: one due to Grade 1 myocarditis and another due to Grade 3 acute hepatitis. No treatment-related deaths were reported (Rohrberg et al., 2026).
Pharmacokinetics and Antidrug Antibodies
Rilvegostomig systemic exposure increased in a near dose-proportional manner between 70 and 1,500 mg. Treatment-emergent antidrug antibodies were detected in 41.0% of patients. High-titer treatment-emergent antibodies were associated with approximately a 42% lower steady-state area under the concentration-time curve. However, the investigators reported that the available study data did not demonstrate clear evidence that antidrug antibody development affected safety or clinical efficacy across the evaluated doses (Rohrberg et al., 2026).
Interpretation and Next Steps
ARTEMIDE-01 is an early-phase trial, and its findings require appropriately cautious interpretation. The study was open-label and nonrandomized, and its analyses were descriptive, with no formal statistical comparisons between dose groups performed. The objective response rate at the recommended Phase II dose was 5.6%, meaning most patients did not experience an objective tumor response. At the same time, the population had already been exposed to checkpoint inhibitor therapy, and all patients had documented primary or secondary resistance. The observation that several responses were durable provides a signal for further investigation rather than evidence of established efficacy in this setting (Rohrberg et al., 2026).
The development program has already moved beyond the checkpoint inhibitor-resistant population. Parts C through E of ARTEMIDE-01 are evaluating rilvegostomig in checkpoint inhibitor-naïve NSCLC, including patients with squamous and nonsquamous disease and PD-L1 tumor proportion scores of at least 1% or at least 50%. Rilvegostomig is also being studied in several Phase III programs, including ARTEMIDE-Lung04 (NCT06868277) against pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 expression ≥50%, and ARTEMIDE-Lung02 (NCT06692738) and ARTEMIDE-Lung03 (NCT06627647) against pembrolizumab plus chemotherapy in first-line metastatic squamous and nonsquamous NSCLC, respectively. TROPION-Lung10 (NCT06357533) is evaluating rilvegostomig in combination with datopotamab deruxtecan (Dato-DXd), and TROPION-Lung12 (NCT06564844) is evaluating rilvegostomig with or without Dato-DXd in the adjuvant setting after complete resection of stage I adenocarcinoma NSCLC (Rohrberg et al., 2026).
Mariana Brandao, Medical Oncologist at Jules Bordet Institute and a study author, described the publication as "both professionally and personally rewarding," noting that "what began as an early-phase study has contributed to the development of a drug that is now being evaluated across multiple phase III clinical trials." She highlighted that the trial demonstrated "a favorable safety and tolerability profile, with no dose-limiting toxicities observed and no maximum tolerated dose reached," as well as "evidence of clinical activity in a heavily pretreated population, including durable disease control in a subset of patients."
The central question now moves to randomized development: whether coordinated PD-1 (搜索) and TIGIT (搜索) inhibition can translate from target engagement and isolated durable responses into a clinically meaningful advantage for patients with lung cancer.