The combination of pumitamig (BNT327/BMS986545) and chemotherapy elicited responses when used in the first-line treatment of patients with non–small cell lung cancer (NSCLC), showing efficacy in both histologies and at each PD-L1 expression level, according to findings from the phase 2 ROSETTA Lung-02 study (NCT06712316) presented at the 2026 ASCO Annual Meeting.1
The regimen was found to have an acceptable toxicity profile in both histologies with no new safety signals observed. Two grade 3 VEGF-related events were reported, which included a bleeding event that had resolved; no grade 4 or 5 events occurred. Moreover, 2 grade 3 immune-related adverse effects (irAEs) were reported with the combination.
In all patients (n = 40), the combination elicited an unconfirmed overall response rate (uORR) of 72.5% (95% CI, 56.1%-85.4%) and a confirmed ORR (cORR) of 62.5% (95% CI, 45.8%-77.3%). The confirmed best overall responses (BORs) were complete response (CR) for 2.5% of patients, partial response (PR) for 60.0% of patients, and stable disease (SD) for 37.5% of patients.
In those with nonsquamous NSCLC (n = 21), the overall uORR was 71.4% (95% CI, 47.8%-88.7%) and the cORR was 57.1% (95% CI, 34.0%-78.2%). The cBORs were PR for 57.1% of patients, and SD for 42.9% of patients. The confirmed disease control rate (cDCR) was 100.0% (95% CI, 83.9%-100.0%). Those within this group who received the 1400-mg dose of pumitamig (n = 11), the uORR, cORR, and cDCRs were 81.8% (95% CI, 48.2%-97.7%), 63.6% (95% CI, 30.8%-89.1%), and 100.0% (95% CI, 71.5%-100.0%), respectively. The cBOR was PR for 63.6% of patients and SD for 36.4% of patients. In those given the 2000-mg dose (n = 10), the uORR was 60.0% (95% CI, 26.2%-87.8%), the cORR was 50.0% (95% CI, 18.7%-81.3%), and the cDCR was 100.0% (95% CI, 69.2%-100.0%). Half of patients had a PR as their cBOR and the other half had SD.
In patients with squamous disease (n = 19), the overall uORR with the regimen was 73.7% (95% CI, 48.8%-90.9%) and the cORR was 68.4% (95% CI, 43.4%-87.4%). In this group, 5.3% of patients had a CR as their cBOR, 63.2% had a PR, and 31.6% had SD. The cDCR was 100.0% (95% CI, 82.4%-100.0%). In those who received pumitamig at 1400 mg (n = 11), the uORR, cORR, and cDCRs were 81.8% (95% CI, 48.2%-97.7%), 72.7% (95% CI, 39.0%-94.0%), and 100.0% (95% CI, 71.5%-100.0%), respectively. Here, 72.7% of patients had a PR as their cBOR and 27.3% had SD. Lastly, in those who were given the 2000-mg dose (n = 8), the uORR was 62.5% (95% CI, 24.5%-91.5%) and the cORR was 62.5% (95% CI, 24.5%-91.5%); cBORs were CR for 12.5% of patients, PR for 50.0% of patients, and SD for 37.5% of patients. The cDCR in this group was also 100.0% (95% CI, 63.1%-100.0%).
When broken down by PD-L1 expression levels, those with a tumor proportion score (TPS) below 1% (n = 21) experienced an uORR of 61.9% (95% CI, 38.4%-81.9%) and a cORR of 47.6% (95% CI, 25.7%-70.2%). Those with a PD-L1 TPS ranging from 1% to 49% (n = 9), experienced a uORR of 77.8% (95% CI, 40.0%-97.2%) and a cORR of 77.8% (95% CI, 40.0%-97.2%); those with a TPS of 50% or higher experienced a uORR of 100.0% (95% CI, 54.1%-100.0%) and a cORR of 100.0% (95% CI, 54.1%-100.0%). For those who had missing PD-L1 information (n = 4), the uORR was 75.0% (95% CI, 19.4%-99.4%) and the cORR was 50.0% (95% CI, 6.8%-93.2%).
“Pumitamig combined with chemotherapy showed encouraging results in patients with both major types of NSCLC, squamous or nonsquamous, including patients whose cancer is usually harder to treat,” Solange Peters, MD, PhD, and co-authors, noted in a presentation of the data. “These early results support moving this treatment into a larger phase 3 trial to better understand how well it works when combined with traditional chemotherapy in comparison to current standard treatment and to further assess its safety profile in patients with advanced NSCLC.”
Peters is a full professor, and chair of medical oncology and the thoracic malignancies programme in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland.
Pumitamig Shows Early Promise Across NSCLC Subtypes
- Pumitamig plus chemotherapy produced encouraging response rates in first-line advanced NSCLC, achieving a confirmed ORR of 62.5% and disease control rates of 100% across both squamous and nonsquamous histologies.
- Clinical activity was observed regardless of PD-L1 expression, including patients with PD-L1 tumor proportion scores below 1%, a population with significant unmet need.
- The anti–PD-L1/VEGF-A bispecific antibody demonstrated a manageable safety profile, with low rates of severe VEGF-related and immune-related toxicities and no new safety signals reported.
What is the current unmet need in the first-line setting for advanced NSCLC?
The emergence of immune checkpoint inhibition in the first-line setting has led to prolonged survival for patients with NSCLC, but long-term outcomes are suboptimal.2 As such, “more efficacious first-line treatment options are needed for [patients with] advanced NSCLC, particularly in [those] with a PD-L1 TPS [of less than] 1%,” Peters noted.1
The anti–PD-L1 AND VEGF-A bispecific antibody, pumitamig, is hypothesized to localize and concentrate dual blockade within the tumor microenvironment, relieve immunosuppression, and normalize tumor vasculature. Prior findings have revealed that pumitamig monotherapy has led to a uORR of 47.1% and a DCR of 100% in patients with advanced nonsquamous NSCLC with a PD-L1 TPS below 1%; the median progression-free survival in these patients was 13.6 months.2 In patients with advanced squamous NSCLC, the agent induced a uORR of 61.5% and a DCR of 92.3%.
What was the trial design of ROSETTA Lung-02?
The multicenter, open-label, randomized, phase 2/3 study included patients with histologically or cytologically confirmed stage IIIB/IIIC or IV NSCLC who did not have actionable genomic alterations.1 They were required to have at least 1 measurable lesion by RECIST v1.1 and an ECOG performance status no higher than 1. They could not have previously received systemic therapy for NSCLC but they could have any PD-L1 status.
The phase 2 portion of the research broke patients out into two subgroups: those with nonsquamous (n = 23) and squamous (n = 21) disease. Patients were randomly assigned 1:1 to receive pumitamig at 1400 mg or 2000 mg plus carboplatin at area under the curve 5 and pemetrexed at 500 mg/m2 given for 4 cycles every 3 weeks followed by maintenance. The primary end points for this phase were safety, ORR, and best percentage change in tumor size.
The median age in all patients included (n = 44) was 66.0 years (range, 41-87). About one-third (34.1%) were female and more than half were White (63.6%); most were former smokers (84.1%) and had an ECOG performance status of 1 (61.4%). In terms of histology, 52.3% of patients had nonsquamous disease and 47.7% had squamous disease. Brain metastases were present in 9.1% of patients and 13.6% of patients had liver metastasis.
When looking at PD-L1 TPS, overall, 58.3% of patients had a TPS below 1%, 25.0% had a TPS of 1% to 49%, and 16.7% had a TPS of 50% or higher. In the nonsquamous subgroup, 78.9% had a PD-L1 TPS below 1%, 5.3% had a TPS ranging from 1% to 49%, and 15.8% had a TPS of at least 50%. In the squamous subgroup, 35.3% of patients had a TPS under 1%, 47.1% had a TPS of 1% to 49%, and 17.6% had a TPS of 50% or higher. “[There was] a high number of patients with a PD-L1 [TPS of less than] 1%, particularly in nonsquamous histology,” Peters noted.
The data cutoff date for the analysis was April 13, 2026, and the overall median follow-up was 9.0 months (range, 0.0-12.8).
What biomarker data were reported from the analysis?
In evaluable patients with nonsquamous NSCLC (n = 20), the baseline circulating tumor DNA (ctDNA) detection rate was 60% (n = 12); in evaluable patients with squamous disease (n = 16), this rate was 87.5% (n = 14). Peters reported that at day 1 of cycle 3, all evaluable patients, which included 11 patients with nonsquamous disease and 14 patients with squamous disease, had experienced a ctDNA reduction from baseline with comparable molecular response (MR) rate observed between the histologies.
In the nonsquamous group, 64% of patients achieved MR100 clearance, 73% had MR90, and 100% had MR50. In the squamous group, these rates were 71%, 93%, and 100%, respectively.
What additional safety results were reported with pumitamig?
Any treatment-related adverse effects (TRAEs) occurred in 93.0% of patients overall (n = 43); they were grade 3 or higher for 48.8% of patients. TRAEs determined to be related to pumitamig occurred in 76.7% of patients and 23.3% were grade 3 or higher. TRAEs led to discontinuation for 18.6% of patients and proved fatal for 1 patient. Moreover, immune-related treatment-emergent adverse effects (TEAEs) occurred in 37.2% of patients, VEGF-related TEAEs were reported in 55.8% of patients, and hemorrhage/bleeding TEAEs occurred in 20.9% of patients.
Any TRAEs related to pumitamig that were experienced by at least 10% of patients were hypertension (1400 mg: 22.7%; 2000 mg: 23.8%), proteinuria (13.6%; 23.8%), anemia (13.6%; 19.0%), hypothyroidism (13.6%; 9.5%), fatigue (13.6%; 9.5%), diarrhea (13.6%; 0%), and rash (9.1%; 14.3%).
“[There was a] manageable safety profile at each dose, and bleeding events were low with only 1 [case being] grade 3,” Peters noted.
What is next for pumitamig?
“Based on the overall trial data, a pumitamig 1500-mg every-3-week flat dose was chosen for the phase 3 part,” Peters concluded. ROSETTA Lung-02 is recruiting in first-line nonsquamous and squamous NSCLC.
The agent is also being explored in combination with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC) as part of a phase 1b/2 trial (NCT05918133). At a median follow-up of 19.5 months (95% CI, 18.0-20.6), pumitamig plus nab-paclitaxel (Abraxane) elicited an ORR of 78.6% (95% CI, 63.2%-89.7%) in patients with previously untreated, locally advanced or metastatic TNBC, irrespective of PD-L1 status (n = 42).3
“In this study, the ORRs were identical for the PD-L1–positive and PD-L1–negative populations, showing that we have hope for an immunotherapeutic strategy for our PD-L1–negative patients, who have not had that before,” Sarah Sammons, MD,4 of Dana-Farber Cancer Institute and Harvard Medical School, told OncLive® in an exclusive interview:5
