How New Therapies Are Changing the Game for Small Cell Lung Cancer

Dr. Charles M. Rudin highlighted new small cell lung cancer therapies, including T cell engagers, antibody-drug conjugates, as well as emerging cell, radiotherapy and combination approaches, during an oral presentation at the CURE Educated Patient® Lung Cancer Summit, held in tandem with the 2025 PER® New York Lung Cancer Symposium.

Rudin is the deputy director at Memorial Sloan Kettering Cancer Center in New York.

He noted, “If we take a step back and look globally at how many people in the United States are getting this disease, what do things look like over time? These [numbers] actually look substantially better than they did 20 to 30, years ago.”

How T-cell engagers are changing the standard of care for small cell lung cancer

T cell engagers are generating a lot of interest in cancer treatment, according to Rudin. One drug, Imdelltra (tarlatamab), has already become part of standard care, and while it may not be the most effective in the class, these therapies are showing real activity and could play an important role in the future of cancer care.

“The way these work is they bind to the cancer cell, and they bind to the immune cell and they bring it to them,” Rudin stated during his presentation. “When the immune cell gets in contact with the cancer cell in this way, it activates and it kills tumor cells.”

A clinical trial with 509 patients tested Imdeltra as a second-line treatment against standard chemotherapy. Patients were randomly assigned to receive Imdelltra or one of three chemotherapy options: topotecan, lurbinectedin or amrubicin.

The results, published in The New England Journal of Medicine in 2025, showed that Imdelltra outperformed chemotherapy. More patients on Imdelltra stayed free of disease progression over time, and more were alive at 21 months compared with those receiving chemotherapy.

“I think this is very early data,” Rudin continued. “The median follow up on this trial was less than a year, 11 months. There's already a clear benefit, but I think the real benefit would be again, in the tail, for long term survivors here. This has changed the standard of care, and I would consider this to be the drug to use, if at all possible, in the context of recurrent, small cell lung cancer.”

In addition, Rudin noted that while the results are not yet FDA-approved, moving treatment earlier into the maintenance phase is showing positive outcomes.

Early results from a study presented by at the 2025 World Conference on Lung Cancer looked at adding Imdelltra to standard maintenance immunotherapy. Patients received either Imdelltra with Tecentriq (atezolizumab) or Imdelltra with Imfinzi (durvalumab). Overall, the combinations showed strong outcomes: 82% of patients were alive at one year, the median overall survival was 25.3 months and 34% were free from disease progression at 12 months.

How antibody-drug conjugates are changing the standard of care for small cell lung cancer

Antibody-drug conjugates are also changing the standard of care for small cell lung cancer according to Rudin. A study by Rudin, published in the Journal of Clinical Oncology in 2025, evaluated I-DXd (datopotamab deruxtecan) in patients with recurrent small cell lung cancer.

“These are sort of smart approaches,” Rudin explains. “They're an antibody that's directed against the tumor, so the antibody binds to the cancer, and it's bringing a chemotherapy drug to the tumor. And the idea here is that with this sort of smart approach, you're FedExing the chemo to the tumor. You're basically directing chemo where it needs to be, avoiding some of the systemic toxicities of chemotherapy by concentrating it in the tumor.”

The results showed that many patients experienced a reduction in tumor size, with the overall median survival reported at 10.3 months. Patients in the second line of therapy and those in the third line or later both saw benefits, regardless of prior treatments or the presence of brain metastases.

Another antibody-drug conjugate that Rudin highlighted was ABBV-706.

In 2020, research presented at WCLC evaluated the investigational agent ABBV-706 in patients diagnosed with recurrent small cell lung cancer. The study involved two distinct dosing cohorts: one group of 40 patients received a dose of 1.8 milligram per kilogram (mg/kg), and a second group of 38 patients received a higher dose of 2.5 mg/kg.

The clinical findings indicated that the majority of treated patients experienced a reduction in their overall tumor burden. Specifically, many individuals across both dose levels achieved substantial decreases in tumor size during the trial period. While a broad trend toward tumor shrinkage was observed, a minority of patients showed either minor changes or, in some cases, experienced tumor growth.

“Almost every single patient is having tumor shrinkage,” Rudin stated. “Really good to see — we haven't had drugs like this before for patients with small cell lung cancer, neither of these is yet FDA approved. Neither one of these is yet prescribable. I think I-DXd is on the cusp, and we're sort of awaiting word for the FDA of whether this is going to make the bar.”

Other positive trends in small cell lung cancer

A phase 3 study, known as the IMforte study, investigated the addition of Zepzelca (lurbinectedin) to immunotherapy maintenance therapy. Patients were randomized to receive either Tecentriq plus Zepzelca or Tecentriq alone.

The primary endpoint of progression-free survival was significantly improved in the combination arm, with a median of 5.4 months versus 2.1 months with Tecentriq alone. Overall survival also showed a positive trend, with a median of 13.2 months for the combination versus 10.6 months for Tecentriq alone. These results were published in The Lancet in 2025.

“I think this is a win, but it's a small win for me, as we don't really raise the tail on the curve here,” Rudin stated during the presentation. “The large majority of patients are still not really benefiting the long term from this. We buy a few months. I'm looking for more than a few months here.”

Reference

1. “Advances in the treatment of small cell lung cancer,” by Dr. Charles M. Rudin. CURE EP Lung Cancer Summit.

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