A clinical trial now recruiting at Roswell Park Comprehensive Cancer Center aims to redefine therapeutic stratification and improve outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC), a highly aggressive neuroendocrine tumor that is frequently metastatic at presentation. While median overall survival historically has been limited (approximately 7–11 months), in recent years those numbers have begun trending higher with the use of immunotherapy. Conducted through the SWOG Cancer Research Network, this study represents one of the first biomarker-directed, subtype-based clinical trials, matching targeted therapies to tumor-specific molecular and transcriptional features.
Prantesh Jain, MD, FACP, Assistant Professor of Oncology in the Department of Medicine at Roswell Park, serves as Site Principal Investigator of the phase 2 clinical trial, called PRISM (NCT06769126), the PRecIsion in SCLC Via a Multicohort Study.
“Small cell lung cancer has long been treated as a single disease, but biologically it is heterogeneous,” explains Dr. Jain. “PRISM allows us to align therapy with tumor subtype and molecular vulnerability. By integrating biomarker testing into treatment selection, we are moving beyond a one-size-fits-all approach toward a more rational, precision-based strategy for patients with extensive-stage disease.”
The study proceeds in two steps. In Step 1, all patients receive standard induction chemo-immunotherapy with a platinum agent and etoposide, plus durvalumab (brand name Imfinzi), an anti-PDL-1 checkpoint inhibitor. During induction, tumor specimens undergo biomarker testing to determine each patient’s ES-SCLC molecular subtype.
In Step 2, after completing induction, patients are assigned to one of three cohorts based on their subtype and randomized within their cohort to maintenance durvalumab alone or durvalumab in combination with one of these biomarker-directed agents:
- Cohort C (Subtype I): Monalizumab (IPH2201), an anti–NKG2A antibody that enhances natural killer cell–mediated antitumor activity, added to maintenance durvalumab
- Cohort A (Subtypes A or N & SLFN11-positive, or Subtype P): Saruparib (AZD5305), a next-generation PARP inhibitor that exploits defective DNA damage repair in tumor cells, added to maintenance durvalumab
- Cohort B (Subtypes A or N & SLFN11-negative): Ceralasertib (AZD6738), an ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor that targets the DNA damage response and exploits replication stress in tumor cells, added to maintenance durvalumab
Investigators will focus primarily on comparing progression-free survival between treatment arms within each cohort. Secondarily, they will determine what percentage of patients can have their disease subtype identified, track overall survival among the groups and evaluate toxicity of the different regimens.
BROADCASTMED