IMM2510 Induces Early Efficacy in Advanced, Immunotherapy-Exposed Squamous NSCLC

IMM2510 led to responses in approximately one-third of patients with advanced squamous non–small cell lung cancer (NSCLC) who had previously received both chemotherapy and immunotherapy, according to data from the dose-escalation and cohort-expansion portions of the phase 1 IMM2510-01 trial (NCT05972460) presented during the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.1

As of August 6, 2025, the median follow-up was 3.75 months in efficacy-evaluable patients with squamous NSCLC (n = 17). The objective response rate (ORR) was 35.3% (n = 6; 95% CI, 14.21%-61.67%), all of which were partial responses (PRs). Seven (41.2%) cases of stable disease (SD) and 4 (23.5%) cases of progressive disease (PD) also occurred.

The disease control rate (DCR) was 76.5% (n = 13 of 17; 95% CI, 50.10%-93.19%), and the median duration of response was 7.59 months (95% CI, 4.07-not available [NA]). The median progression-free survival was 9.4 months (95% CI, 1.87-NA).

“Based on these findings, a phase 2 study evaluating IMM2510 in combination with chemotherapy in advanced NSCLC is in progress to further assess its therapeutic potential,” lead study author Zhengbo Song, MD, of Zhejiang Cancer Hospital in Hangzhou, China, and coauthors wrote in a poster presentation.

What Was the Basis for the IMM2510-01Trial, and What Is IMM2510?

Preclinical and clinical research has shown that the addition of anti-VEGF antibodies to immune checkpoint inhibitors can result in improved antitumor activity compared with either modality alone. Bispecific antibodies targeting PD-L1 and VEGF have also shown higher efficacy compared with either agent alone or the combination of the two.

IMM2510 is a novel bispecific antibody fusion protein targeting both PD-L1 and VEGF that is under evaluation in IMM2510-01, an ongoing, multicenter, open-label trial. The study is evaluating the agent’s safety, efficacy, recommended phase 2 dose (RP2D), and pharmacokinetic activity in patients with advanced solid tumors.

During the dose-escalation portion of the trial, 9 dose levels were tested. No dose-limiting toxicities occurred, and 20 mg/kg of IMM2510 administered every 2 weeks was selected as the RP2D. The dose-expansion portion of the trial is underway and is enrolling patients with relapsed/refractory soft tissue sarcoma (STS), NSCLC, and other solid tumors. Per the trial design, tumor assessments will be performed every 8 weeks per RECIST 1.1 criteria, and safety will be evaluated according to CTCAE 5.0 criteria.

Data from the dose-escalation phase and STS cohort were previously presented at the 2025 ASCO Annual Meeting.2

What Were the Baseline Characteristics of the Squamous NSCLC Population?

As of June 13, 2025, 23 patients with squamous NSCLC had been treated with IMM2510.1 All patients had received prior immunotherapy and chemotherapy. Seven patients received the agent during dose escalation (3 mg, n = 2; 6 mg, n = 1; 10 mg, n = 4), and 16 patients received the agent in cohort expansion at the RP2D.

The median age was 61 years, and 17 patients (73.9%) had an ECOG performance status of 1. All patients had metastatic sites in the lung (n = 10; 43.5%), liver (n = 4; 17.4%), bone (n = 7; 30.4%), or brain (n = 2; 8.7%). The median number of prior lines of systemic therapy was 2 (range, 1-5). Tumor PD-L1 tumor proportion scores (TPS) were less than 1%, between 1% and 49%, and 50% or greater in 7 (30.4%), 8 (34.8%), and 3 (13.0%) patients, respectively. All patients had received prior PD-(L)1 therapy plus chemotherapy, and 6 (26.1%) patients had received prior anti-VEGF therapy.

How Did the Agent Fare According to PD-L1 TPS Category?

Additional efficacy data were presented according to PD-L1 TPS. In evaluable patients in the PD-L1 TPS less than 1% group (n = 5), the ORR was 20% (n = 1; 95% CI, 0.51%-71.64%); this response was a PR. One case (20%) of SD and 3 cases (60%) of PD were also reported. The DCR was 40% (n = 2; 95% CI, 5.27%-85.34%).

Among evaluable patients in the PD-L1 TPS between 1% and 49% group (n = 6), the ORR was 50% (n = 3; 95% CI, 11.81%-88.19%); all responses were PRs. Three cases (50%) of SD also occurred. The DCR rate was 100% (n = 6; 95% CI, 54.07%-100%).

Of evaluable patients in the PD-L1 TPS 50% or greater group (n = 3), the ORR was 33.3% (n = 1; 95% CI, 0.84%-90.57%); this response was a PR. One case (33.3%) each of SD and PD was also reported. The DCR rate was 66.7% (n = 2; 95% CI, 9.43%-99.16%).

Among the 3 patients with unknown PD-L1 TPS, the ORR was 33.3% (n = 1; 95% CI, 0.84%-90.57%); this response was a PR. Two cases (66.7%) of SD were also reported. The DCR was 100% (n = 3; 95% CI, 29.24%-100%).

What Was the Safety Profile of the Bispecific Antibody?

With respect to safety, all patients experienced treatment-emergent adverse effects (TEAEs). Thirteen patients (56.5%) experienced grade 3 or greater TEAEs, and 10 patients (43.5%) experienced grade 3 or greater treatment-related adverse effects (TRAEs). One patient (4.3%) experienced a TEAE that led to treatment discontinuation.

Grade 3 or greater TRAEs included decreased platelet count (8.7%), decreased lymphocyte count (8.7%), and infusion-related reaction (8.7%), all of which were clinically manageable, Song noted.

The incidence of VEGF-related TRAEs was low. No grade 3 or greater hypertension occurred, and 1 case (4.3%) each of grade 3 proteinuria and pulmonary hemorrhage occurred. There were no cases of treatment-related deaths.

Enrollment for the cohort of patients with squamous NSCLC is ongoing, from which additional pharmacodynamic and pharmacokinetic analyses will be performed.

Disclosures: No disclosures were listed for Song.

References

1. Song Z, Wang P, Zhang Y, et al. IMM2510, an anti-PD-L1/VEGF bispecific antibody fusion protein for advanced IO-pretreated SQ-NSCLC: a phase I study. Presented at: International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract 4792.
2. Xu H, Gao S, Jia R, et al. IMM2510, an anti-PD-L1/VEGF bispecific antibody fusion protein, in patients with R/R STS: a phase Ib expansion study. J Clin Oncol. 2025;43(suppl 16):11545. doi:10.1200/JCO.2025.43.16_suppl.1154