FDA Grants Accelerated Approval to Tarlatamab-Dlle for Extensive-Stage Small Cell Lung Cancer

Efficacy was evaluated in 99 patients with relapsed or refractory extensive-stage small cell lung cancer with disease progression following platinum-based chemotherapy who were enrolled in DeLLphi-301 [NCT05060016], an open-label, multicenter, multicohort study. Patients with symptomatic brain metastases, interstitial lung disease or non-infectious pneumonitis, and active immunodeficiency were excluded. Patients received tarlatamab-dlle until they experienced disease progression or unacceptable toxicity.

The major efficacy outcome measures were overall response rate (ORR) per RECIST 1.1 and duration of response (DOR), as assessed by blinded independent central review. ORR was 40% (95% CI = 31, 51), and median DOR was 9.7 months (range = 2.7, 20.7+). 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 (defined as progression less than 90 days after their last dose of platinum therapy) and 31% (95% CI = 18, 47) in 42 patients with platinum-sensitive SCLC (defined as progression 90 days or later after their last dose of platinum therapy).

The prescribing information for tarlatamab-dlle includes a boxed warning for serious or life-threatening cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). The most common adverse reactions reported in more than 20% of patients were CRS, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. The most common grade 3 or 4 laboratory abnormalities reported in at least 5% of patients were decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.

The recommended tarlatamab-dlle schedule is an initial dose of 1 mg administered as an IV infusion over 1 hour on cycle 1, day 1, followed by 10 mg on cycle 1, days 8 and 15, then every 2 weeks thereafter until patients experience disease progression or unacceptable toxicity. View the full prescribing information for tarlatamab-dlle (https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761344s000lbl.pdf).

FDA’s review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Brazilian Health Regulatory Agency, Health Canada, Israel’s Ministry of Health, and United Kingdom’s Medicines and Healthcare Products Regulatory Agency. The application reviews are ongoing at the other agencies.

Tarlatamab-dlle was granted accelerated approval based on overall response rate and duration of response. Continued approval may be contingent on verification of clinical benefit.

The application and review used the Real-Time Oncology Review (https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid). FDA approved the application one month ahead of its goal date.

The application was granted priority review, breakthrough designation, and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).