THE FOOD AND DRUG ADMINISTRATION (FDA) approved an immunotherapy drug called tarlatamab—sold under the name Imdelltra and made by drug company Amgen—for extensive stage small cell lung cancer (SCLC). Extensive stage refers to SCLC that has spread throughout the lung, to the other lung, or to distant parts of the body, according to the American Cancer Society.
The FDA’s accelerated approval of Imdelltra was based on data from a phase II trial called DeLLphi-301, published in the Nov. 30, 2023, issue of the New England Journal of Medicine. The approval is specifically for patients with advanced SCLC who had disease progression during or after receiving platinum-based chemotherapy.
In the trial, 220 patients were assigned to receive either 10 or 100 milligrams (mg) of Imdelltra. Researchers found response rates, noting how many people had tumors shrink in response to treatment, of 40% in the group getting the 10-mg dose and 32% in the 100-mg group. This led them to recommend the lower dose for future use and research. The median overall survival for the 10-mg group was 14.3 months.
“The most impressive thing is that this major shrinkage [of tumors] was associated with a very durable response so that the shrinkage stayed that way for many months, or even years in some patients,” says David Carbone, a medical oncologist specializing in lung cancer at Ohio State University Comprehensive Cancer Center in Columbus, who had patients enrolled in the trial.
“That durability is something that I have never seen in my entire 30 years of lung cancer therapy,” Carbone says.
Much of the progress in treating lung cancer in recent years has been for the more common non-small cell lung cancer, which accounts for about 80% to 85% of all lung cancer cases, according to the American Cancer Society. The less common small cell type has been notoriously difficult to treat, Carbone says. While finding a chemotherapy regimen that worked for many patients with SCLC was one of the early successes in lung cancer therapy, patient responses were almost always temporary.
“Once the cancer came back after chemotherapy, it was usually very resistant to other types of therapies and these patients often recurred and rapidly died,” Carbone explains, adding these therapies would “only cause temporary remissions that last just a few months.”
Imdelltra, a type of cancer therapy known as a bispecific T-cell engager, uses a different approach.
According to Carbone, it is “one molecule that has two binding domains.” It binds to a protein called delta-like ligand 3 (DLL3) and another called CD3. DLL3 is expressed on the surface of lung cancer cells and connected to the function of small cell tumors, he explains, while CD3 is expressed on T cells or immune cells.
Imdellta “links the cancer to the immune cell and activates the T cell right next to the cancer cell,” ultimately causing its death, Carbone explains.
The study results indicate progress for a disease that had previously not had many great treatment options, but more data are needed to understand the long-term benefits of Imdelltra.
“While these results are encouraging, we know from experience that enthusiasm needs to be curbed until data is available from a randomized study with an appropriate control arm,” Michael Menefee, an oncologist at Cleveland Clinic Cancer Institute in Ohio, who was not associated with the study, explains. Until then, Menefee says, Imdelltra will be a “welcome addition” to the toolbox doctors have to treat extensive stage SCLC.
One concern with immunotherapies is that activating the immune system against cancer can cause side effects like cytokine-release syndrome, which was the most common side effect reported with Imdelltra.
Cytokine-release syndrome is “a common type of toxicity seen with immunotherapies. It’s mostly flu-like symptoms and some low-grade fever,” Carbone explains. He says his patients who were enrolled in phase I of the DeLLphi-301 trial tended to have these side effects after the first few doses, but they cleared up as treatment continued.
Imdelltra is currently approved only for very advanced SCLC, but there is hope to use it with earlier stage disease in the future.
Menefee says that it’s currently being compared to the standard chemotherapy as a second-line treatment for patients with relapsed SCLC, as a first-line therapy in combination with chemotherapy and another immunotherapy, and “in the potentially curative setting” as an additional therapy given to patients with earlier stage disease after treatment with chemotherapy and radiation.
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