Researchers have published the results of a clinical trial evaluating the efficacy of an immunotherapy drug in treating a particularly aggressive form of lung cancer. Tarlatamab produced promising results, demonstrating antitumor activity and improving survival rates in patients for whom previous treatments hadn’t worked.
Like all cancers, small cell lung cancer (SCLC) begins at the cellular level and causes cancerous cells to reproduce rapidly and uncontrollably. However, its rapid growth makes SCLC the most aggressive form of lung cancer, and not many people with it are still alive five years after diagnosis, making identifying an effective treatment all the more important.
A Phase 2 clinical trial led by researchers at the Karl Landsteiner Private University of Health Sciences, Austria, evaluated an immunotherapy drug, tarlatamab, for antitumor activity and survival in patients with SCLC who’d previously received two lines of treatment.
“[T]he evaluation of this global study with 220 affected people showed that with a dosage of 10 mg tarlatamab, antitumor activity began and persisted in 40% of the affected people treated in this way,” said Sabin Handzhiev, one of the study’s co-authors.
Although most patients with SCLC respond to first- and second-line treatments, the disease usually progresses within a few months. Currently, there’s no approved drug that could be used as a third-line treatment option. The researchers are hopeful that tarlatamab may provide patients with another option.
A monoclonal antibody, tarlatamab works by binding to both the delta-like 3 (DLL3) protein on cancer cells and the CD3 protein on the patient’s own T cells. This brings the T cells into proximity with the cancer cells, leading to lysis – the rupture and disintegration – of the cancer cells.
“DD3 represents an interesting therapeutic target for patients with small cell lung cancer, as over 85% of those affected have this surface molecule on the cancer cells, while its expression in normal cells is minimal,” Handzhiev said.
For the trial, 220 patients received tarlatamab at one of two doses, 10 mg or 100 mg, every two weeks. The median follow-up was a little over 10 months for both groups. The primary endpoint was objective response, defined as the proportion of patients with a complete or partial response to treatment.
An objective response occurred in 40% of patients who received 10 mg and 32% in the 100 mg group. The duration of the objective response was at least six months in 59% of patients. At the time of data cutoff, the objective response was ongoing in 55% of patients in the 10 mg group and 57% in the 100 mg group. The researchers observed a median of 4.9 months for progression-free survival in the 10 mg group and 3.9 months in the 100 mg group. Estimates of overall survival at nine months were 68% and 66%, respectively.
“In order to be able to classify these values, one must understand that those affected have a really poor outlook with the current third-line treatment in clinical trials,” Handzhiev said. “Only around 20% of them even respond to a third-line therapeutic agent – and the median overall survival time is well over six months. Tarlatamab represents a promising alternative, especially since 58% of those treated responded to the 10 mg dose for at least six months.”
The most common adverse event was cytokine-release syndrome (CRS), which was seen in 51% of the 10 mg patients and 61% of the 100 mg patients. CRS is an acute systemic inflammatory syndrome characterized by fever, nausea, fatigue, and body aches. It occurs when the immune system reacts to immunotherapy drugs more aggressively than it should. Decreased appetite (29% and 44%, respectively) and elevated body temperature (35% and 33%) were the other common adverse events. Only 3% of patients discontinued tarlatamab treatment due to adverse events.
Overall, the trial results demonstrate the potential of monoclonal antibodies to link T cells with cancer cells to treat a solid tumor.
The study was published in The New England Journal of Medicine.
Source: PR&D
