The FDA on Thursday granted accelerated approval to Amgen’s bispecific T cell engager tarlatamab in small cell lung cancer, an aggressive disease that makes up roughly 10% to 15% of lung cancer cases.
It’s the first bispecific T cell engager to be approved for a major solid tumor, according to Amgen. The FDA approved the treatment for patients with extensive-stage small cell lung cancer whose disease progressed despite chemotherapy.
Jean-Charles SoriaAmgen will market tarlatamab as Imdelltra, and has set a list price of $31,500 for the first cycle of treatment and $30,000 for following cycles.
The treatment comes with boxed warnings around serious immune reactions and neurotoxicity that have been seen with immunotherapies. In clinical trials, 51% of patients who received the approved dose experienced cytokine release syndrome, a serious condition caused by immunotherapies where the immune system overactivates. However, the vast majority of cases were of low severity.
“The journey to get a T cell engager approved in a solid, common cancer, it’s 10 years in the making,” Amgen’s SVP of oncology Jean-Charles Soria told Endpoints News ahead of the approval.
T cell engagers are of growing interest and use in the field of cancer immunotherapy. Previously approved bispecifics have been mostly in blood cancers like lymphoma and multiple myeloma, as well as a rare eye cancer. Last year, the FDA approved four new bispecific T cell engagers.
“If you take in parallel CAR-Ts, they have been having results in hematological malignancies, but they have not cracked the solid tumor field,” Soria said. “This will give an edge to T cell engagers, which are off-the-shelf.”
The antibody-based therapies come with two arms: one that binds a T cell, and another that binds a tumor cell. By bringing the two cells close together, the hope is that the T cell will kill the tumor cell. Imdelltra specifically targets DLL3, a target expressed in most small cell lung cancers.
Deadly disease, poor prognosis
Small cell lung cancer is typically treated with checkpoint inhibitors and chemotherapy, but patients have few options beyond that. Smoking is closely linked to higher risk of the disease, and the five-year survival rate is 7%, according to the American Cancer Society.
In a Phase 2 clinical trial, Amgen studied people whose cancer had progressed following at least two previous treatments — a group where typical survival time is well under a year. The people who received Imdelltra survived for a median of over 14 months.
“The data is fairly impressive,” Dana-Farber Cancer Institute lung cancer doctor Pasi Jänne told Endpoints ahead of the approval. “It’s definitely a welcome therapy to the small cell [lung cancer] armamentarium, where it’s only traditionally been chemotherapy and some modest impact of immune checkpoint inhibitors.”
Jänne was not involved in the clinical study.
The study tested two doses — a 10 mg dose and a 100 mg dose — but the lower dose surprisingly led to a higher response rate of 40%, compared with 32% for the higher dose. Based on these data, the FDA approved the lower 10 mg dose, as well as a 1 mg step-up dose.
The approval comes roughly one month ahead of schedule, as the FDA’s decision deadline was June 12.
As part of the accelerated approval, Amgen must provide confirmatory data showing Imdelltra’s benefit. For that, the company is using the Phase 3 DeLLphi-304 study, where the bispecific will be compared to standard treatment in patients who have already received chemotherapy as their first line of therapy.
Boehringer Ingelheim has a similar bispecific T cell engager in early-stage clinical trials, and Novartis and Legend Biotech are collaborating on a DLL3-targeted CAR-T cell therapy.
Editor’s note: This story was updated with the list price of Imdelltra.