Phase 3 Randomized Open‑Label Trial of ABBV‑706 versus Standard of Care in Relapsed/Refractory Small Cell Lung Cancer

The primary objective is to demonstrate the superiority of ABBV-706 versus standard of care (topotecan, lurbinectedin, or amrubicin) in adults with relapsed/refractory Small Cell Lung Cancer, as measured by objective response rate assessed by blinded independent central review per RECIST v1.1 and by overall survival; confirming a higher ORR and prolonged OS would substantiate an improved therapeutic benefit in this high‑risk population. Secondary objectives include:

• Evaluation of safety and tolerability of ABBV-706 compared with standard of care.
• Assessment of efficacy through progression‑free survival and duration of response by blinded independent central review.
• Investigation of the impact on patient‑reported physical functioning and quality of life using the EORTC‑QLQ‑C30 questionnaire.

A total of 406 participants were enrolled, comprising both male and female adults. The age distribution encompassed the full adult range, including younger and older adult categories as defined by the study’s age‑range codes. All subjects had a confirmed diagnosis of Small Cell Lung Cancer that was relapsed or refractory after prior systemic therapy. Eligibility required an Eastern Cooperative Oncology Group performance status of 0 to 1, measurable disease per RECIST v1.1, and suitability for receiving the standard‑of‑care comparator (topotecan, lurbinectedin, or amrubicin). Participants must have progressed on previous platinum‑based chemotherapy regimens, with or without checkpoint inhibitor therapy, and, if present, brain metastases had to be treated or asymptomatic and not require steroids exceeding a prednisone equivalent of 10 mg/day. General health status was otherwise required to be adequate for study treatment, and no specific lifestyle restrictions (e.g., diet or physical activity) were stipulated in the selection criteria.

The study is a Phase 3, randomized, open‑label, multicenter trial evaluating intravenous Small Cell Lung Cancer patients who have relapsed or are refractory to prior therapy. Eligible participants are screened for histologic confirmation, ECOG performance status 0‑1, measurable disease per RECIST v1.1, and prior exposure to platinum‑based chemotherapy and tarlatamab; those meeting criteria undergo a screening visit, after which randomization assigns them to receive either the investigational monoclonal antibody ABBV‑706 or a standard‑of‑care comparator (topotecan, lurbinectedin, or amrubicin). Treatment is administered on Day 1 of each 21‑day cycle; study visits occur at baseline (pre‑dose), every 6 weeks for tumor imaging and safety assessments, with patient‑reported outcomes collected at Week 12, and continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoints are objective response rate assessed by blinded independent central review and overall survival; secondary endpoints include progression‑free survival, duration of response, and quality‑of‑life measures. Participants remain in the trial for the duration of treatment and a follow‑up period required for survival assessment, with early discontinuation permitted for adverse events, disease progression, or patient choice. The overall recruitment period spans from August 2026 to September 2030, and individual involvement may extend for several months to years depending on clinical outcomes.

The investigational product ABBV-706 is a humanised IgG1 monoclonal antibody directed against SEZ6 and conjugated to a cytotoxic moiety. It is supplied as a solution for infusion and administered intravenously. The protocol specifies a dose of 00 mg per administration; dosing is performed on a defined schedule (e.g., every 21 days) as outlined in the study treatment plan. Administration is conducted under clinical supervision with infusion parameters recorded, and adherence to the dosing schedule is monitored through treatment logs and source documentation.

The comparator arm utilizes the chemotherapeutic agent topotecan, which may be given either orally or intravenously according to standard‑of‑care practice. Each formulation is administered at a dose of 00 mg per administration, with the route (oral or IV) selected based on investigator discretion and patient suitability. Dosing follows the conventional schedule for relapsed/refractory small cell lung cancer (e.g., daily for five consecutive days in a 21‑day cycle). Compliance with the comparator regimen is assessed by reviewing medication administration records, pill counts for the oral formulation, and infusion documentation for the intravenous formulation.

Efficacy in the study of subjects with Small Cell Lung Cancer will be evaluated using both primary and secondary clinical endpoints. The primary efficacy parameters are objective response, expressed as overall response rate (ORR) assessed by blinded independent central review (BICR) according to RECIST v1.1 criteria, and overall survival (OS). These endpoints will be measured through radiographic imaging reviewed centrally and survival follow‑up until the end of the study.

Secondary efficacy assessments include progression‑free survival (PFS) and duration of response (DoR), both derived from BICR per RECIST v1.1, as well as patient‑reported outcomes at week 12. Physical functioning and global health status/quality of life will be quantified using the physical functioning domain and the GHS/QoL scale of the EORTC QLQ‑C30 questionnaire, respectively. Imaging for response assessments will be performed at protocol‑specified intervals, and the EORTC QLQ‑C30 will be administered at baseline and at week 12 to capture changes from baseline.