Fresh findings from ES-SCLC drug trial

The interaction between PD-L1 (red) on the surface of a cancer cell and the immune checkpoint PD-1 (blue) on a T-cell inhibits T-cell killing of tumor cells.

Amgen shared new data from its phase 1b DeLLphi-303 study of Imdelltra (tarlatamab-dlle), a first-in-class, delta-like ligand 3 (DLL3)-targeting Bispecific T-cell Engager (BiTE) molecule. The company shared these recent results at the 2024 World Conference on Lung Cancer (WCLC) in San Diego.

The global, multicenter, open-label study evaluated the efficacy and safety of Imdelltra combined with PD-L1 inhibitors in first-line maintenance for adults who have extensive-stage small cell lung cancer (ES-SCLC). Additional results from phase 2 of the clinical trial (DeLLphi-301), which evaluated the drug’s use in patients with previously treated ES-SCLC, will also be presented at the conference.

“Earlier this year, the FDA approved Imdelltra for patients with extensive-stage small cell lung cancer who progressed on or after platinum-based chemotherapy,” said Jay Bradner, MD, executive vice president, Research and Development, and chief scientific officer at Amgen, in a press release. “We are thrilled to share results showing long-term sustained benefit in this setting as well as initial evidence supporting a combination approach in front-line maintenance therapy. These data support our goal to deliver an effective targeted immunotherapy to more patients living with this aggressive cancer.”

According to Amgen, Imdelltra combined with a PD-L1 inhibitor as first-line maintenance therapy in ES-SCLC demonstrated a manageable safety profile with sustained disease control and positive survival outcomes. Key findings from the phase 1b study include:

  • Imdelltra plus a PD-L1 inhibitor: positive benefit; risk profile with no new or unexpected safety findings
  • Imdelltra plus durvalumab: disease control rate (DCR) of 62.5% (95% CI: 45.8-77.3) and median duration of disease control (DoDC) that was Not Estimable (95% CI: 3.9, NE)
  • Imdelltra plus atezolizumab: DCR of 62.5% (95% CI: 47.4-76.0) and median DoDC of 7.2 months (95% CI: 5.6, NE)
  • Following a median time of three-and-a-half months from first-line chemoimmunotherapy to first-line maintenance:
    • Imdelltra plus durvalumab showed a nine-month overall survival (OS) of 91.8% (95% CI: 76.6-97.3) and median progression-free survival (mPFS) of 5.3 months (95% CI: 3.5-NE)
    • Imdelltra plus atezolizumab showed a nine-month OS of 86.7% (95% CI: 70.3-94.4) and mPFS of 5.6 months (95% CI: 3.5-8.5)

“Tarlatamab has been a major breakthrough for patients with extensive-stage small cell lung cancer, who have had limited options for the past 30 years, and these data are impressive as a potential first-line maintenance treatment as well,” said Sally Lau, MD, oncologist and assistant professor of medicine, Perlmutter Cancer Center, NYU Grossman School of Medicine. “In particular, tarlatamab in combination with a PD-L1 inhibitor showed exciting safety and efficacy, which strongly supports continued evaluation in the ongoing phase 3 DeLLphi-305 trial.”

In patients with ES-SCLC who received Imdelltra plus durvalumab, treatment-related adverse events (TRAEs) resulted in dose interruptions in 15% of cases and discontinuation in 8% of patients. TRAEs in the Imdelltraplus atezolizumab treatment group led to dose interruptions in 17% of cases and discontinuation of Imdelltra in 4% of patients. 

Additionally, cytokine release syndrome (CRS) was mostly grade one to two, occurred primarily in cycle one and was generally manageable with supportive care. Immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent overall, with a lower incidence and severity observed in the Imdelltra plus durvalumab treatment arm compared to Imdelltra plus atezolizumab treatment arm.

Long-term follow-up data from the DeLLphi-301 phase 2 study revealed sustained anticancer activity and a manageable safety profile with IMDELLTRA in patients who previously underwent platinum-based chemotherapy for ES-SCLC.

Among 100 patients treated with Imdelltra 10 mg biweekly, Amgen reported that the objective response rate (ORR) was 40%, with nearly half of the responders maintaining their response at data cutoff. Stable disease was observed in 30% of the patients, and the median duration of disease control was 6.9 months (95% CI, 5.4-8.6). Median OS for this group was 15.2 months and was similar regardless of progression-free interval (<90 days or 90+ days) after first-line platinum-based chemotherapy. 

Researchers verified long-term tolerability of the therapy and identified no new safety concerns. Based on the comprehensive data, Amgen said it supports the continued use of Imdelltra in this patient population, underscoring its clinical significance.

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