Cooperative Trial Aims to Bring Precision Medicine to SCLC Subgroups

According to Anne Chiang, MD, PhD, the phase 2 SWOG 2409 (S2409) PRISM trial (NCT06769126) is a large trial aimed at bringing precision medicine to at least 800 patients with personalized regimens based on SCLC subtype and Schlafen 11 status.

Chiang, an associate professor of Medical Oncology and Thoracic Oncology, as well as the Associate Cancer Center Director of Clinical Initiatives at Yale School of Medicine, discussed biomarkers her team is prioritizing among patients enrolled in early phase clinical trials to better select immunotherapies or targeted agents. The discussion was contextualized by a presentation at the Chemotherapy Foundation Symposium (CFS), hosted by Physician’s Education Resource®, LLC, where she spoke about “Cases and Conversations: Transforming Small Cell Lung Cancer Treatment Through Emerging Evidence and Expert Insights (Spotlight CE Session).”1

She began by introducing the S2409 PRISM trial, which she explained was a large trial aimed at integrating biomarkers into precision medicine for patients undergoing treatment for SCLC.2 She explained that as patients undergo induction chemoimmunotherapy, tissue samples will be collected to determine SCLC subtype, SCLC-A, SCLC-N, SCLC-P or SCLC-I, as well as Schlafen 11 protein status.

She continued by expressing that patients will then be randomly assigned to receive durvalumab maintenance with or without a targeted agent determined by the results of the biomarker test. Chiang suggested that the trial her team is undertaking builds upon the work of 2 MD Anderson-based clinicians, Carl M. Gay, MD, PhD and Lauren A. Byers, MD, who published a manuscript proposing that matching baseline tumor subtypes to therapy might exhibit better duration of response and overall response outcomes among those with SCLC.3

Finally, Chiang expressed that the S2409 trial is aiming to enroll patients with brain metastases to undergo treatment off trial before entering the trial to enable them to receive immediate treatment without running the risk of trial exclusion. She concluded in highlighting that this cooperative group trial may help patients being treated in community practices access novel agents for SCLC.

Transcript:

We have a great trial that has opened through the cooperative groups. It’s the phase 2 S2409 PRISM trial. It's going to include over 800 patients, and this is going to integrate biomarkers so that we can offer precision medicine for our patients [with SCLC]. In this trial, the patients will undergo induction chemoimmunotherapy during the first 4 cycles or so, and during that time, we will get tissue from the patients to figure out what subtype they are, if they are subtype SCLC-A, SCLC-N, SCLC-P or SCLC-I, and also biomarker use [including] what status they are for Schlafen 11 protein.

Then, based on these biomarkers, they will be randomized to a targeted agent plus durvalumab and maintenance vs durvalumab maintenance therapy alone. This is exciting, because we are going to be able to see this. This builds on [the work of] Carl M. Gay, MD, PhD, and Lauren A. Byers, MD at MD Anderson, showing that there are subtypes that benefit. For example, [patients with] subtype SCLC-I benefit from the use of immunotherapy.

We are going to try to target the therapy to the patients this trial. In addition, it is going to allow patients with asymptomatic brain metastases to come on and allow them to get their first cycle off trial and then join the trial after that, in case they were [quite] sick and had to get their first trial immediately. We are making the effort to make the trial fit the patient, instead of making the patient for the trial. Ultimately, there are a lot of patients throughout the country, because this is a cooperative group trial, so community patients who are going to be accessing novel agents for SCLC and hopefully we can learn a lot from this.

References

1. Rudin CM, Chiang A, Sands JM. Cases and conversations: transforming small cell lung cancer treatment through emerging evidence and expert insights (Spotlight CE Session). Presented at: 43rd Annual Chemotherapy Foundation Symposium (CFS); November 12-14, 2025; New York, NY.
2. Using biomarker tests to select and test new, personalized treatments for extensive stage small cell lung cancer, PRISM study. ClinicalTrials.gov. Updated November 5, 2025. Accessed November 24, 2025. https://tinyurl.com/yc5kv9vz
3. Gay CM, Stewart CA, Park EM, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021;39(3):346-360. doi:10.1016/j.ccell.2020.12.014