The combination of tarlatamab (Imdelltra, Amgen) and a PD-L1 inhibitor after first-line chemo-immunotherapy showed promise as a maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC), with a manageable safety profile, according to the phase Ib DeLLphi-303 trial.
Among 88 patients, the median overall survival (OS) was 25.3 months, with a 12-month OS rate of 82% and an 18-month rate of 75%, reported Kelly G. Paulson, MD, PhD, of the Providence-Swedish Cancer Institute in Seattle.
Paulson called the OS results "unprecedented," noting they are "truly exciting and compared very favorably to the 10 to 15 months in prior reported studies," during the World Conference on Lung Cancer (WCLC) in Barcelona.
The study was also published in Lancet Oncology.
"Wow," said invited discussant Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City. "I think this looks really good. Even in maintenance, a 2-year survival plus is really striking. We have not seen that before, ever, in our patients with small cell lung cancer."
"We need to see phase III, we need all that data, and it will be coming," he added. "I know I'm supposed to be critical, but it's a wow. There are caveats ... and all of those caveats are relevant. We shouldn't compare [these data] to phase III data ... but, bottom line, I'm pretty impressed, and these curves look better than I thought they would."
Of note, the most common grade 3-4 adverse events were hyponatremia (10%), anemia (8%), and neutropenia (7%). Serious adverse events occurred in 57% of patients, with the most common being cytokine release syndrome (24%), pyrexia (7%), immune effector cell-associated neurotoxicity syndrome (5%), and pneumonia (5%). There were no deaths due to treatment-related adverse events.
In explaining the study's background, Paulson noted that current clinical practice guidelines recommend continuation of maintenance anti-PD-L1 therapy -- atezolizumab (Tecentriq) or durvalumab (Imfinzi) -- following first-line chemo-immunotherapy until disease progression or intolerable toxicity.
In the maintenance setting, median OS with atezolizumab was 12.5 months in the IMpower133 trial, and 13.2 months with atezolizumab and lurbinectedin (Zepzelca) in the IMforte trial.
Tarlatamab -- a delta-like ligand 3-directed bispecific T-cell engager -- has improved survival in patients with previously treated SCLC. In the initial report of this study presented at last year's WCLC, the 9-month OS rate was 89% with tarlatamab plus anti-PD-L1 therapy as first-line maintenance.
In the current analysis, median progression-free survival (PFS) was 5.6 months, with a 12-month PFS rate of 34%. The objective response rate was 24%, and the disease control rate was 60%. Median duration of response was 16.6 months.
Paulson and colleagues pointed out that the objective response and disease control rates were notable given that the baseline scans were obtained after completion of standard-of-care first-line chemo-immunotherapy.
"Thus, responses in this context represented an additional tumor response beyond that observed after platinum-etoposide chemotherapy plus a PD-L1 inhibitor," they wrote, adding that 36% of patients maintained disease control for at least 1 year.
"The activity demonstrated in the DeLLphi-303 study, including sustained disease control and overall survival surpassing that reported with current and emerging standards of care, supports ongoing evaluation of tarlatamab plus PD-L1 inhibitor therapy as first-line maintenance therapy in ES-SCLC," they concluded, noting that the randomized phase III DeLLphi-305 study, which will assess this regimen versus standard of care, "has the potential to change the first-line ES-SCLC treatment landscape."
For this study, 88 patients from 30 centers in 13 countries with histologically or cytologically confirmed ES-SCLC and no previous systemic treatment for ES-SCLC were enrolled after four to six cycles of first-line platinum-etoposide chemotherapy and a PD-L1 inhibitor (unless they had no access to PD-L1 inhibitors).
Mean age was 64, 63% were men, 70% were white, and 19% were Asian. All patients had an Eastern Cooperative Oncology Group performance status score of 0 or 1, 72% were former smokers, and 24% were current smokers.
From August 2022 through January 2024, they received tarlatamab 10 mg intravenously once every 2 weeks, after an initial tarlatamab 1-mg dose, with atezolizumab or durvalumab intravenously as maintenance until disease progression.
The median time from start of standard-of-care first-line chemo-immunotherapy to start of tarlatamab maintenance was 3.6 months. The median follow-up from the start of maintenance was 18.4 months, and the median exposure to tarlatamab was 35 weeks.
Disclosures
The study was funded by Amgen.
Paulson reported research funding to their institution from Amgen, Bristol Myers Squibb, Merck, Iovance Biotherapeutics, and Immunocore, and consulting fees from Bristol Myers Squibb.
Rudin had no disclosures.
