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Small cell lung cancer (SCLC) research continues to progress at an unprecedented rate. Exciting news emerged from the 2025 World Congress on Lung Cancer, with six studies showing how innovative therapies have the potential to give people with lung cancer better outcomes and longer survival than ever before.
After decades with little treatment progress, it was remarkable to see an entire session dedicated to the treatment of newly diagnosed extensive-stage SCLC (ES-SCLC) (also known as first-line treatment). Below, we are pleased to highlight these new treatment approaches.
Combining Drugs to Increase Effectiveness
Lurbinectedin + Atezolizumab (IMforte Study): This is really a one-two punch: lurbinectedin damages cancer cell DNA while atezolizumab (immunotherapy) removes the "brakes" that stop our immune system from attacking tumors. A phase 3 study tested this combination as first-line maintenance therapy (treatment given after initial chemotherapy + immunotherapy to keep cancer away longer).
The combination kept working for about four months on average with manageable side effects when patients proactively received medications to take care of the side effects.
Using Bispecifics
Bispecifics are interesting medicines. They are typically antibodies that can target two proteins at the same time.
Tarlatamab, a T-cell recruiter: This bispecific acts like a cellular matchmaker, binding immune T-cells on one side and cancer cells (via a protein called DLL3) on the other, which forces them together so the T-cells destroy the cancer. Used as first-line maintenance in a phase 1b study, it provided a survival benefit of 25.3 months on average. Most patients experienced flu-like symptoms initially, but these decreased over time as their bodies adjusted.
Pumitamig, a tumor-microenvironment modifier: This bispecific antibody simultaneously blocks two cancer survival mechanisms—immune system suppression (by blocking the PD-L1 protein) and blood vessel growth (by blocking the VEGF protein that feeds tumors). Combined with chemotherapy as first-line treatment in a phase 2 study, 87% of patients responded, with tumors shrinking an average of 47%.
Making Radiation More Precise
It is well-known that SCLC is extremely sensitive to radiation treatment. Now, scientists have combined the cancer-killing potential of radiation with the ability of antibodies to target cancer cells—creating radioligand therapy (RLT).
RYZ101: This first-of-its-kind RLT uses a radioactive element (actinium-225) attached to an antibody that seeks out somatostatin receptor-expressing (SSTR2+) solid tumors. Once it finds its target, it delivers powerful, short-range radiation that kills cancer cells while sparing healthy tissue nearby. A phase 1b study in newly diagnosed extensive-stage SCLC shows promising early safety results and continues to be tested in clinical trials.
Options for ES-SCLC that have stopped responding to available treatments are also being explored. Antibody drug conjugates (or ADCs) are a new class of medicines being developed. ADCs can precisely identify a cancer cell and deliver a toxic chemotherapy in a targeted manner.
I-DXd: I-DXd is an ADC that finds a protein called B7-H3 on the surface of SCLC cells, latches onto the cancer cells, and then releases a powerful toxin directly into the tumor. A phase 2 study tested this treatment in people who had already tried 1-2 previous treatments. Nearly half of patients (48%) saw their tumors shrink, and the treatment provided an average of 10.3 months of survival. The main concern was lung inflammation in about 12% of patients, but doctors are getting better at managing these side effects.
ABBV-706: This drug works in a similar way to I-DXd, but it binds to a different target, SEZ6, on the surface of the cancer cell and then delivers a DNA-damaging payload. In a phase 1 study of patients whose previous treatments had stopped working, the best dose (1.8 mg/kg) worked especially well in 62% of people enrolled in the trial who hadn't previously received certain chemotherapy drugs.
These treatments represent fundamentally different ways to fight SCLC - from recruiting one’s own immune system to delivering precision radiation. This diverse range of options offers tremendous hope for progress in the coming months and years for treating people who are living with SCLC.