Tarlatamab: A New Therapy Approved for Small-Cell Lung Cancer

There is a new agent shown to increase progression-free survival and median overall survival in patients with relapsed or refractory small-cell lung cancer (SCLC). Tarlatamab (brand name: Imdelltra) is the first bispecific T-cell engager approved for solid tumors. 

Tarlatamab has been granted accelerated approval due to the promising response rate and duration of response demonstrated in clinical trials. Ongoing approval for this indication may depend on the confirmation and further characterization of clinical benefits in one or more confirmatory studies.

This new advancement reinforces the clinical practice of knowing your patient’s cancer in all aspects to offer the best available therapy. 

Dr. Mark Kris, a leading thoracic oncologist at Memorial Sloan Kettering Cancer Center, asserts that biomarker testing in lung cancer should be the standard of care for every patient before beginning treatment. 

“We have a test that says if the drugs will work or not, and we just can’t get over this hump of making it a standard of care for everybody … You should use the best tests we have available, get the most precise information, and deliver the best treatment on day one,” Dr. Kris tells SurvivorNet Connect. 

Dr. Greg Riely, an attending physician at Memorial Sloan Kettering Cancer Center, echoed this stance: “Understanding those results is key to picking first-line therapy and is important for our patient’s understanding of their potential disease outcomes. How we get molecular testing, and how we get biomarker testing is critical.”

The Data 

The FDA granted accelerated approval to tarlatamab based on data from the Phase 2 DeLLphi-301 clinical trial. This study evaluated the drug in patients with SCLC who had failed two or more previous treatments and received a 10 mg dose every two weeks. 

“We’ve seen amazing new drugs brought forward in small cell lung cancer … Now, tarlatamab is an interesting drug that brings together the T-cell and a marker on small cell lung cancer cells, the DLL3 target,” Dr. Riely explains.

The trial results showed that tarlatamab at the 10 mg dosage (N=99) achieved a significant objective response rate (ORR) of 40% (95% Confidence Interval [CI]: 31–51) and a median duration of response (DoR) of 9.7 months (CI: 2.7–20.7+). The median overall survival (mOS) was 14.3 months, with final survival data yet to be fully matured.

“We see that this compound can bring those things together (T-cell and DLL3) and activate the immune system to help target and wipe out small cell lung cancer cells. It’s a totally new category of agent for patients with lung cancer and one we look forward to using in the clinic,” Dr. Riely affirms. 

Dosage Administration: Key Considerations

Tarlatamab should be administered as a one-hour intravenous infusion, following a step-up dosing schedule as outlined in the prescribing information, to minimize cytokine release syndrome (CRS) risk and severity. During the first treatment cycle, patients should receive recommended medications before and after the administration infusions to reduce the risk of CRS, as detailed in the prescribing information. 

Administration should only be carried out by a qualified healthcare professional who is equipped to manage severe reactions such as CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). Due to the potential for these serious side effects, patients should be closely monitored for 22 to 24 hours after starting the medication on Cycle 1, Day 1, and Cycle 1, Day 8. This monitoring must take place in a suitable healthcare setting to ensure immediate response to any adverse reactions. 

Additionally, it is recommended that patients stay within one hour of a healthcare facility for a total of 48 hours following the start of the infusion on Cycle 1, Day 1, and Day 8. Patients should be accompanied by a caregiver during this time. Prior to each dose, healthcare providers should evaluate complete blood count, liver enzymes, and bilirubin levels to ensure patient safety. Hydration is also advised prior to each administration of tarlatamab to support patient tolerance of the treatment.

Safety Alerts: What to Know

Cytokine release syndrome (CRS), including severe or life-threatening reactions, may occur in patients treated with tarlatamab. To minimize the risk and severity of CRS, initiate therapy with the step-up dosing regimen. Tarlatamab should be withheld until CRS resolves or permanently discontinued, depending on the severity of the reaction.

Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may also be severe or life-threatening, has been reported in patients receiving tarlatamab. Patients should be closely monitored for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Prompt management is essential, and treatment should be withheld until symptoms resolve or permanently discontinued based on the severity of the toxicity.

Given its potential benefits and manageable adverse effects, tarlatamab presents a viable treatment option for patients who have experienced progression after frontline chemotherapy. In the absence of contraindications, it should be considered for any patient with small cell lung cancer (SCLC) who has not responded to initial platinum-based therapies. The choice to pursue tarlatamab or explore other therapeutic options should be made collaboratively between the patient and their physician, considering the patient’s overall health, prior treatments, and individual preferences.