| Drug Name |
IMDELLTRA™ (tarlatamab-dlle) |
| Active Ingredient |
tarlatamab |
| Date of Approval |
5/16/24 |
| Manufacturer |
Amgen, Inc |
| Approval Pathways and Indications |
Approval Pathway: BLA
Indication:
IMDELLTRA™ is a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager indicated for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). |
| Therapeutic Class |
Immunotherapy |
| Formulation |
Injection for Intravenous Infusion |
| MoA |
Tarlatamab-dlle is a bispecific T-cell engager that binds to DLL3 expressed on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. Tarlatamab-dlle causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells. Tarlatamab-dlle had anti-tumor activity in mouse models of SCLC. |
| Dosing and Administration |
For injection: 1 mg or 10 mg of lyophilized powder in a single-dose vial for reconstitution and further dilution.
• Administer as an intravenous infusion over 1-hour.
• Administer IMDELLTRA™ according to a step-up dosing schedule to reduce the risk of cytokine release syndrome.
• Administer concomitant medications as recommended.
• Monitor patients from the start of the IMDELLTRA™ infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.
• Recommend patients to remain within 1-hour of an appropriate healthcare setting for a total of 48 hours from the start of the infusion with IMDELLTRA™ following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver. |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
Small cell lung cancer (SCLC) is one of the most aggressive solid tumor malignancies, with a median survival of approximately 12 months following initial therapy and a 3% five-year relative survival rate for ES-SCLC. Current second-line treatments impart a short duration of response (median DoR: 3.3–5.3 months) and limited survival (median OS: 5.8-9.3 months), while current third-line treatments for SCLC, which consist primarily of chemotherapy, yield a short median DoR of 2.6 months and a median OS of 4.4-5.3 months. Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.
Tarlatamab-dlle is a bispecific T-cell engager (BiTE) for the treatment of SCLC that has progressed on or after platinum-based chemotherapy. It marks the first BiTE therapy approved for a major solid tumor and the first therapeutic option for extensive-stage SCLC. As the first and only DLL3-targeting BiTE, Tarlatamab-dlle activates the patient's own T cells to attack DLL3-expressing tumor cells.
IMDELLTRA™ is Amgen’s second BiTE on the market. Over the last decade, the FDA has approved Blincyto for five types of acute lymphoblastic leukemia (ALL) (Last year, sales for the treatment were up 48% to $861 million).
The IMDELLTRA™ label includes a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), in addition to warnings and precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity. The most common (> 20%) adverse reactions reported among patients were CRS (55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%), and nausea (22%). |
| Expected Market Launch Date |
Unavailable |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Amgen has priced IMDELLTRA™ at $31,500 for the first cycle and $30,000 for subsequent cycles. With a cycle of treatment lasting 28 days and the median duration of treatment extending for 5.5 cycles, the average cost per patient would come to $166,500. |
| Product Discontinuation |
N/A |
| Clinical Trials |
The efficacy of IMDELLTRA™ was evaluated in Study DeLLphi-301 [NCT05060016], an open-label, multicenter, multi-cohort clinical trial. Eligible patients were required to have relapsed/refractory SCLC with disease progression after receiving previous treatment with platinum-based chemotherapy and at least one other line of prior therapy, an ECOG Performance Status of 0 or 1, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
A total of 99 patients received IMDELLTRA™ intravenously at an initial dose of 1 mg on Cycle 1 Day 1 followed by 10 mg on Days 8, 15, and every 2 weeks thereafter until disease progression or unacceptable toxicity. All patients received prior platinum-based chemotherapy (median two lines); 74% received prior anti-PD-(L)1 therapy (including 59% who received anti-PD[L]1 therapy in combination with platinum based chemotherapy in the frontline setting); 51% received prior topoisomerase I inhibitor (including 20% who received topotecan). Platinum sensitivity status, defined by time to progression after first line platinum therapy, was known for 69/99 patients. Twenty-seven patients (27%) had platinum-resistant SCLC, defined as time to progression < 90 days after first line platinum therapy, while 42 patients (42%) had platinum-sensitive SCLC. Tumor assessments were performed every 6 weeks for the first 48 weeks and every 12 weeks thereafter.
The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) as evaluated by Blinded Independent Central Review (BICR) according to RECIST v1.1. Of the 69 patients with available data regarding platinum sensitivity status, the ORR was 52% (95% CI 32, 71) in 27 patients with platinum-resistant SCLC and 31% (95% CI 18, 47) in 42 patients with platinum-sensitive SCLC.
The most common treatment-emergent adverse event (TEAE) associated with tarlatamab-dlle administration was cytokine release syndrome (CRS), which occurred in 49% of patients in the 10-mg group and 61% in the 100-mg group. CRS primarily occurred during the first cycle and was mostly grade 1 or 2. Grade 3 CRS was seen in 5.7% of patients treated with the 100 mg dose.
TEAEs that led to either dose interruption or reduction were reported in 14% of patients treated with the 10 mg dose and 29% in those treated with the 100 mg dose. |
| Sources |
1. Dunleavy K. Amgen’s “Watershed” Lung Cancer Drug Nabs FDA Nod in deadly, tough-to-treat form of the disease. Fierce Pharma. May 17, 2024. Accessed May 17, 2024. https://www.fiercepharma.com/pharma/fda-nod-amgens-watershed-lung-cancer-drug-could-make-it-rain.
2. FDA APPROVES IMDELLTRA™ (TARLATAMAB-DLLE), THE FIRST AND ONLY T-CELL ENGAGER THERAPY FOR THE TREATMENT OF EXTENSIVE-STAGE SMALL CELL LUNG CANCER. Amgen. May 16, 2024. Accessed May 16, 2024. https://wwwext.amgen.com/newsroom/press-releases/2024/05/fda-approves-imdelltra-tarlatamabdlle-the-first-and-only-tcell-engager-therapy-for-the-treatment-of-extensivestage-small-cell-lung-cancer
3. FDA grants accelerated approval for Imdelltra (tarlatamab-dlle) for the treatment of extensive-stage small cell lung cancer. Drugs.com. Accessed May 17, 2024. https://www.drugs.com/newdrugs/fda-grants-accelerated-approval-imdelltra-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer-6271.html. |