KEY TAKEAWAYS
- DeLLphi-301 is a phase 2, open-label study to evaluate tarlatamab in patients with R/R SCLC after two or more lines of prior treatment.
- The trial’s primary aim is to assess the (ORR) per RECIST 1.1 as assessed by a blinded independent central review.
- The trial evaluates the antitumor activity of tarlatamab in SCLC patients based on several secondary measures, including DOR, PFS, DCR, OS, safety and tolerability, immunogenicity, pharmacokinetics.
- The trial is being conducted at sites in North America, Asia, and Europe, with enrolled subjects and ongoing enrollment.
Rapid expansion and early metastasis are hallmarks of SCLC. Platinum-based first-line chemotherapy has a high initial response rate, but the disease often returns. A promising therapeutic target in SCLC is delta-like ligand 3 (DLL3), a Notch ligand that is increased and aberrantly expressed on the cell surface in most SCLC. T cell activation and expansion and T cell-dependent death of tumor cells are induced by the HLE BiTE immuno-oncology medication tarlatamab by binding DLL3 on target cancer cells and CD3 on T cells, producing a cytolytic synapse. Preliminary evidence for tarlatamab efficacy in pretreated individuals with relapsed/refractory SCLC is emerging from an ongoing first-in-human study (NCT03319940), with 20% of patients achieving confirmed partial responses and a duration of response of 8.7 months. Two-and-a-half percent of patients experienced treatment-related adverse events (AEs) of grade ≥ 3 or higher, and 5% discontinued therapy due to AEs. Tarlatamab’s effectiveness and safety profile in SCLC warrants additional research.
Tarlatamab is being tested in individuals with relapsed/refractory SCLC after two or more lines of previous treatment in phase 2, open-label research NCT05060016. Subjects will be randomly assigned to one of two tarlatamab dose groups in Phase 1, the dose characterization phase. Based on the intermediate analysis from Part 1, enrolment in Part 2 will proceed exclusively for the chosen target dose. Adults with histologically or cytologically confirmed SCLC who have had disease progression/recurrence despite two or more lines of prior treatment, including at least one platinum-based regimen (including a PD-L1 inhibitor, if the standard of care, with certain exceptions per protocol), treated brain metastases, ECOG performance status ≤1, and life expectancy ≥ 12 weeks in the investigator’s opinion. For the primary analysis, the gold standard is the objective response rate (ORR) according to RECIST 1.1 as determined by a central, blinded review. Secondary aims include assessing safety and tolerability, immunogenicity, and pharmacokinetics and evaluating anticancer activity by various measures (duration of response, progression-free survival, disease control rate, and duration, and overall survival). The trial is international, with sites in North America, Asia, and Europe recruiting participants.
Source: https://meetings.asco.org/abstracts-presentations/213233
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT05060016
Suresh S. Ramalingam, Myung-Ju Ahn, Hiroaki Akamatsu, Fiona Helen Blackhall, Hossein Borghaei, Horst-Dieter Hummel, Melissa Lynne Johnson, Martin Reck, Yiran Zhang, Danielle Jandial, Sunfa Cheng, Luis G. Paz-Ares/Phase 2 study of tarlatamab, a DLL3-targeting, half life–extended, bispecific T-cell engager (HLE BiTE) immuno-oncology therapy, in relapsed/refractory small cell lung cancer (SCLC)/J Clin Oncol 40, 2022 (suppl 16; abstr TPS8603)DOI10.1200/JCO.2022.40.16_suppl.TPS8603
