Dr Puri on Future Research Directions in SCLC

“It’s such an exciting time to be a researcher in small cell lung cancer. We are looking at more personalized treatments, more targets, and more innovative treatment approaches. [This includes] antibody-drug conjugates that have shown promising responses or are in development.”

Sonam Puri, MD, a thoracic oncologist and clinical medical director at Moffitt Cancer Center, discussed future research directions and ongoing developments in small cell lung cancer (SCLC).

Efforts to develop more personalized treatments and identify additional treatment targets are of great interest in SCLC, Puri began. For example, agents targeting delta-like ligand 3 (DLL3) and SEZ6 have shown promise in preclinical and early-phase trials, she noted. Radiopharmaceuticals are also being developed to interact with targets on the surface of SCLC tumor cells, she added. More sophisticated methods to engage T cells are being examined, including trispecific T-cell activating constructs, as well as approaches to engage other immune cells, Puri said.

, multiple studies examining DLL3-targeted agents for the treatment of patients with SCLC were presented. Preliminary data from a phase 1 trial (NCT06179069) demonstrated that patients who received the DLL3-targeted antibody drug conjugate ZL-1310 (n = 28) achieved an overall response rate (ORR) of 68%, including a complete response (CR) rate of 4%. Findings from a phase 2 study (NCT06283719) showed that the DLL3/DLL3/CD3 trispecific T-cell engager alveltamig (ZG006) produced an ORR of 62.5% (95% CI, 40.6%-81.2%) and a disease control rate of 70.8% (95% CI, 48.9%-87.4%) among patients with refractory SCLC who received the agent at a dose of 10 mg every 2 weeks (n = 24).

Additionally, the ongoing phase 1/2 SKYBRIDGE study (NCT05652686) is examining the anti-DLL3/anti-CD47 bispecific antibody peluntamig (PT217) in patients with SCLC and other neuroendocrine carcinomas. The agent is designed to facilitate tumor cell attack via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. The study is presently enrolling patients at 9 sites across the US and comprises both monotherapy and combination cohorts.

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Sonam Puri, MD, discusses future research directions and ongoing developments in small cell lung cancer.


Sonam Puri, MD, assistant professor, Division of Oncology, Department of Medicine at the University of Utah, and active member of the Lung Cancer Disease Center of Excellence at the Huntsman Cancer Institute, discusses recent research on clinically relevant biomarkers in small cell lung cancer (SCLC). 

In a recent study, Puri and colleagues conducted comprehensive molecular profiling of a total of 437 small cell lung neuroendocrine tumors through the use of next-generation sequencing, RNA sequencing, and immunohistochemistry. Tumors were stratified into 5 subgroups based on the relative expression of 4 transcription factors. The objective of the research was to identify clinically relevant biomarkers of response to immunotherapy in different SCLC subtypes.

It has been known that response to treatment in lung cancer differs depending on where the disease is in the body, Puri says. Central nervous system (CNS) response is a significant factor, and it is important to know whether there is subtype variation in tumors that are isolated from the CNS, according to Puri. More research is needed to fully understand this, Puri says.

Data from the study also indicated that most of the 

-sensitizing mutations occurred in the non–small cell lung cancer subtype, Puri adds. This is hypothesis generating, according to Puri, as it is known that certain drugs used to treat patients with 

 mutations can cause small cell lung cancer (SCLC) transformation. However, a limitation of the database used in the study is that it is unclear whether these tumors were adenocarcinomas before or if they transformed to SCLC; it is also unclear whether they were treated with osimertinib (Tagrisso).

The research did reveal insights regarding biomarkers of response to immunotherapy. For example, tumor mutational burden (TMB) is frequently considered to be a universal marker of immunotherapy response across tumor types, and this study did not find any variation in TMB across the SCLC subtypes, concludes Puri. 

Sonam Puri, MD, discusses recent research on clinically relevant biomarkers in small cell lung cancer. 

Dr. Puri on Clinically Relevant Biomarkers in SCLC

Sonam Puri, MD, thoracic oncologist, Huntsman Cancer Institute, assistant professor, Division of Oncology, Department of Medicine, University of Utah, discusses the rationale to evaluate the real-world multiomic characterization of small cell lung cancer (SCLC) subtypes. 

SCLC is an aggressive type of lung cancer that is associated with poor patient outcomes, says Puri. Although non–small cell lung cancer (NSCLC) treatment is largely driven by biomarkers, SCLC is treated as a single disease, Puri explains. However, emerging research is confirming that, like NSCLC, SCLC can be classified into lineage-defined subtypes based on transcription factors, such as 

Although the data are limited, the subtypes appear to have therapeutic vulnerabilities, so a larger study was conducted using the Caris Life Sciences database, Puri concludes.

Sonam Puri, MD, discusses the rationale to evaluate the real-world multiomic characterization of small cell lung cancer subtypes.  



Sonam Puri, MD

Articles

Dr Puri on Future Research Directions in SCLC

Dr. Puri on Clinically Relevant Biomarkers in SCLC

Dr. Puri on the Rationale to Evaluate Real-World Multiomic Characterization of SCLC Subtypes