Tarlatamab Shows QOL, Symptom Benefits in Previously Treated SCLC

The FDA previously granted accelerated approval to tarlatamab in patients with previously treated extensive-stage SCLC in May 2024 based on data from the DeLLphi-301 study.

Treatment with tarlatamab-dlle (Imdelltra) conferred benefits across various functional and symptom outcomes among patients with previously treated small cell lung cancer (SCLC), according to an analysis of patient-reported outcomes (PROs) from the phase 2 DeLLphi-301 trial (NCT05060016).1

Per European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire (EORTC-QLQ-C30) scores, the most severe symptoms at baseline included fatigue (36.2), insomnia (27.9), and dyspnea (27.5), with low values reported for hemoptysis (2.2), diarrhea (5.8), and sore mouth (5.9). The least square mean change from baseline at cycle 4 for global health status (GHS) or quality of life (QOL) was 3.6 (95% CI, 0.8-6.3) and 12.3 (95% CI, 7.1-16.6) at cycle 12. Additionally, composite dyspnea scores decreased at a mean least square change of –3.9 (95% CI, –6.6 to –1.3) from cycle 4 onwards and –14.4 (95% CI, –20.9 to –7.9) at cycle 12.

Other data showed a trend towards improved emotional and social functioning from baseline. Additionally, investigators noted improvements in alopecia across all cycles, deteriorations in appetite loss, and deteriorating constipation.

The median time to deterioration (TTD) was 7.3 months for cough symptoms and 6.0 months for dyspnea. Treatment produced a median TTD of 1.9 months and 1.4 months for GHS or QOL and physical functioning, respectively. Investigators observed the longest TTD for diarrhea at 12.9 months, arm or shoulder pain at 8.6 months, and pain in other parts at 8.6 months.

Patient Global Impression of Change (PGI-C) scores demonstrated that at least half of patients reported their symptoms becoming “a little better” or “much better” compared with baseline. Additionally, less than 10% of the population rated their symptoms as worse vs baseline, which occurred up to cycles 4 and 6.

“Alongside previously reported antitumor activity, [PROs] show potential benefits across a range of functional and symptom outcomes, including improvements in QOL and reduction in some key symptoms,” lead study author Horst‑Dieter Hummel, MD, from the Translational Oncology/Early Clinical Trial Unit (ECTU) at Bavarian Cancer Research Center, National Center for Tumor Diseases, Comprehensive Cancer Center Mainfranken and University Hospital Würzburg, wrote with coauthors.1 “The demonstration of benefit of tarlatamab with respect to PROs needs confirmation in a comparative phase 3 trial.”

In the dose-selection portion of the phase 2 DeLLphi-301 trial, patients were randomly assigned to receive tarlatamab at 10 mg or 100 mg until disease progression. In the dose-expansion portion, patients received the agent at 10 mg. According to the study authors, the PRO analysis pertained to patients enrolled during the dose-selection and dose-expansion portions of the study.

PROs of interest included the EORTC-QLQ-C30, 13-item lung cancer module (LC13), PRO-CTCAE, and the GP5 question of the Functional Assessment of Cancer Therapy – General Form (FACT-GP5). Investigators collected responses to these items on days 1, 8, and 22 of cycle 1; days 1 and 15 of cycle 2; and every 6 weeks from cycle 3 onwards. The study also included an assessment of median TTD for symptom and functional scales.

Of 100 patients included in the intent-to-treat analysis set, most were male (72%) and from Europe (56%); a majority had metastatic disease (98%) and an ECOG performance status of 1 (74%). Additionally, the median number of prior lines of therapy was 2 (range, 1-6).

Overall, 91% and 92% of patients had evaluable responses for the QLQ-LC13 and QLQ-C3, respectively. Completion rates for these items exceeded 80% for all cycles up to day 1 of cycle 12. Most patients terminated PRO assessments due to progressive disease before death.

During the first 2 cycles of study treatment, up to 6% and 3% reported anxiety and headaches, respectively, occurring “frequently” or “almost constantly.” Severe headaches occurred in up to 15% of patients, although 0% to 8% reported “quite a bit” or “very much” interference.

Up to 1% and 6% of patients, respectively, experienced palpitations and arm or leg swelling “frequently” or “almost constantly.” Additionally, 7% to 21% of patients reported that there was “quite a bit” or “very much” interference regarding overall, arm, or leg swelling.

The incidence of shivering or shaking chills was higher during the first 2 cycles of treatment vs baseline, although less than 5% of patients rated these events as occurring “frequently” or “almost constantly.” The rate of mild or higher severity concentration problems slightly increased from baseline; up to 7% reported severe or very severe concentration issues.

Per FACT-GP5 responses, 92% of patients noted that they were not or a little bit bothered by adverse effects associated with tarlatamab. Within the first 2 cycles, up to 16% reported feeling bothered by toxicities “quite a bit” or “very much”; this rate decreased to less than 8% from cycle 3 onwards.

The FDA previously granted accelerated approval to tarlatamab in patients with previously treated extensive-stage SCLC in May 2024 based on data from the DeLLphi-301 study.2

References

1. Hummel H-D, Ahn M-J, Blackhall F, et al. Patient‑reported outcomes for patients with previously treated small cell lung cancer receiving tarlatamab: results from the DeLLphi‑301 phase 2 trial. Adv Ther. 2025;42:1950-1964. doi:10.1007/s12325-025-03136-4
2. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. May 16, 2024. Accessed April 10, 2025. https://tinyurl.com/48k34rw5