WCLC 2026, day 1: extended-interval and subcutaneous dosing in SCLC, and a 70% early response

Tarlatamab every three or four weeks: lower response rates, median survival not yet reached

DeLLphi-309 (NCT06745323) is a randomised, open-label phase 2 study of tarlatamab, the DLL3-targeting bispecific T-cell engager, in 252 patients with small cell lung cancer that had progressed after first-line platinum chemotherapy. Patients were randomised 1:1:1 to the approved 10 mg every two weeks (n=83), 20 mg every three weeks (n=84) or 30 mg every four weeks (n=85). The primary endpoint was confirmed objective response by blinded independent central review; the analysis is descriptive, with no hypotheses tested.

At the 7 May 2026 cut-off, response rates were 40%, 31% and 27%, median durations of response 8.3 months, 5.6 months and not estimable, and median progression-free survival 4.2, 4.1 and 2.7 months. Six-month overall survival was 72%, 85% and 69%; median overall survival was not reached in the extended-interval arms. Treatment-related cytokine release syndrome occurred in 60–70% of patients across regimens, predominantly grade 1–2, and ICANS of any grade in 6–12%. One death in the 30 mg arm, during a grade 3 ICANS event, was attributed by the investigator to probable cardiac arrhythmia. Dr. Jonathan Goldman (University of California Los Angeles, USA) and colleagues note a baseline imbalance towards higher-risk disease in the 30 mg arm.

Iza-bren at 2.5 mg/kg: a 33% response rate after failure of a third-generation EGFR inhibitor

Iza-bren (izalontamab brenitecan, BL-B01D1) is an antibody-drug conjugate that pairs an EGFR x HER3 bispecific antibody with a topoisomerase 1 inhibitor payload. The randomised dose-expansion cohort of its global phase 1 study (NCT05983432) assigned patients with metastatic EGFR-mutated NSCLC, all previously treated with a third-generation EGFR inhibitor and about two-thirds with platinum chemotherapy, to 1.5, 2.0 or 2.5 mg/kg on days 1 and 8 of a three-week cycle, with mandatory G-CSF prophylaxis.

At 2.5 mg/kg, the chosen phase 3 dose, the objective response rate was 33.3%, the confirmed rate 29.6% and median progression-free survival 6.9 months, figures that agree between the abstract (9 February 2026 cut-off) and the presentation (5 June 2026); median duration of response at that dose was 9.7 months. Grade 3 or higher treatment-related events were mainly anaemia and neutropenia; there were no treatment-related deaths, and pneumonitis occurred in three patients (3.7%). Dr. Alexander Spira (NEXT Oncology Virginia and Virginia Cancer Specialists, Fairfax, USA) said: “These findings support continued development of iza-bren and provide the rationale for advancing the 2.5 mg/kg regimen into the global Phase 3 IZABRIGHT-Lung01 trial for patients with previously treated EGFR-mutated NSCLC.” Median overall survival was not reached at any dose, and the cohort has no comparator arm; the talk is on Monday 14 September.

Pumitamig plus elfetabart drozuntecan: a 70% unconfirmed response rate in small cell lung cancer

BNT324-01 (NCT06892548) is an ongoing global phase 1b/2 study of pumitamig, an investigational PD-L1 x VEGF-A bispecific antibody, combined with elfetabart drozuntecan (elfe-D), a B7H3-directed antibody-drug conjugate, in advanced or metastatic NSCLC or SCLC. By the 7 July 2026 cut-off in the presentation, 279 patients had been treated (201 with NSCLC, 78 with SCLC), with no dose-limiting toxicities.

Among 71 efficacy-evaluable patients with SCLC, the unconfirmed objective response rate across all doses was 70.4% (95% CI 58.4–80.7) and the disease control rate 93.0%. By line of therapy it was 92.3% in first-line (n=13) and 52.4% in third-line or later (n=21). In the whole population treatment-related adverse events occurred in 82.4% of patients and were grade 3 or higher in 26.5%, and two deaths (0.7%; cardiac failure and pulmonary haemorrhage) were judged possibly related to treatment. Of 23 patients with paired ctDNA samples, 96% showed a reduction by cycle 3 and 39% clearance. Dr. Adam Schoenfeld (Memorial Sloan Kettering Cancer Center, New York, USA) said: “The early activity observed with pumitamig plus elfetabart drozuntecan is encouraging, including responses across multiple lines of therapy in small cell lung cancer.” Responses are unconfirmed, median follow-up in SCLC is 3.2 months, no survival endpoint is reported, and NSCLC efficacy is held for a separate presentation.

Local consolidation after nivolumab plus ipilimumab did not extend survival in LONESTAR

LONESTAR (NCT03391869) was an open-label, single-centre randomised phase III trial at MD Anderson Cancer Center, Houston, USA. Immunotherapy-naive patients with stage IV EGFR/ALK wild-type NSCLC received 12 weeks of nivolumab plus ipilimumab; those without progression were randomised to continue the two drugs alone or to receive local consolidation (radiation, with surgery where feasible). The co-primary endpoints were overall survival in all patients and in the oligometastatic subgroup. The trial planned 216 patients but closed after 166 (83 per arm) when the monitoring board found a probability below 0.001 that it would favour consolidation.

At the 15 June 2026 cut-off, median overall survival was 52.8 months without consolidation against 43.2 months with it (HR 1.14; 95% CI 0.75–1.74; P=0.54), and median progression-free survival 24.3 against 31.3 months (HR 0.79; 95% CI 0.54–1.15; P=0.22). In the oligometastatic subgroup medians were 75.8 against 42 months for overall survival and 44.0 against 35.7 for progression-free survival, without hazard ratios. Grade 3 or higher treatment-related events were not increased, but pneumonitis was more frequent (9.5% against 4.9%). Dr. Mehmet Altan (MD Anderson) said: “In this randomized trial, adding local consolidative therapy after induction dual checkpoint blockade was feasible, but it did not improve overall survival or progression-free survival in the overall population or among patients with oligometastatic disease.”

Subcutaneous tarlatamab at 15 mg matched intravenous exposure, with cytokine release syndrome only at grade 1–2

DeLLphi-308 (NCT06598306) is an open-label, multicentre phase 1b study, the first to test tarlatamab by subcutaneous injection, in extensive-stage SCLC that had progressed after at least one platinum-based regimen. Part 1 compared 10 mg and 15 mg every two weeks after a 1 mg step dose; the 15 mg dose, which produced exposure comparable to the approved 10 mg intravenous regimen, went into Part 2, where post-dose monitoring was shortened and then dropped.

The presentation, scheduled for Tuesday 15 September with a 10 June 2026 cut-off, covers 60 patients, 40 of them at 15 mg. In that group cytokine release syndrome occurred in 38% (grade 1 in 28%, grade 2 in 10%, none higher), injection-site reactions in 50%, and no ICANS; across all 60 patients grade 3 or higher treatment-related events occurred in 13%, with no fatal events. The objective response rate at 15 mg was 30%, median progression-free survival 3.7 months (95% CI 1.9–7.0) and median overall survival 11.7 months (95% CI 5.4–not estimable). Dr. Pedro Rocha (Hospital Universitari Vall d’Hebron, Barcelona, Spain) said: “The predominantly low-grade CRS events and preliminary antitumor activity support continued investigation of this more convenient route of administration.” The intravenous comparison is historical, not randomised; the phase 3 DeLLphi-315 study is comparing the two routes directly.

IMpower030: perioperative atezolizumab lengthened event-free survival, but the trial missed its significance threshold

IMpower030 (NCT03456063) is a phase 3 trial of perioperative atezolizumab in resectable stage II to select IIIB NSCLC without EGFR or ALK alterations. Patients were randomised 1:1 to four cycles of neoadjuvant atezolizumab 1200 mg or placebo every three weeks with platinum chemotherapy, then surgery, then 16 cycles of adjuvant atezolizumab or best supportive care. The primary endpoint was event-free survival by independent review in the stage IIB–IIIB population (397 patients).

After a median follow-up of 69.3 months, median event-free survival was 62.8 months with atezolizumab against 34.9 months with placebo; pathological complete response was 29.6% against 8.5% and major pathological response 53.6% against 24.4%. Surgery was cancelled in 11.1% and 10.3% of patients. The abstract states that statistical significance was not reached and that the control arm performed better than historical controls; no new safety signals were seen. Dr. Benjamin Solomon (Peter MacCallum Cancer Centre, Melbourne, Australia) said: “These long-term findings demonstrate clinically meaningful improvements across several important outcomes and further support the role of perioperative immunotherapy for patients with resectable NSCLC.” No hazard ratio, confidence interval or P value for event-free survival is given in the press materials, nor any overall survival figure; the trial’s geography and session code are not stated.

Written by the Lung Summit editorial team.