Lung Cancer Treatment Advances from MSK Presented at 2025 ASCO Meeting

Researchers from Memorial Sloan Kettering Cancer Center (MSK) reported important advances in the treatment of lung cancer at the annual meeting of the American Society of Clinical Oncology (ASCO), held May 30 to June 3 in Chicago. Scientists presented promising results on three different targeted therapies — one for small cell lung cancer and two for non-small cell lung cancer.

Tarlatamab is better than chemotherapy for patients with recurrent small cell lung cancer 

A targeted immunotherapy drug developed to treat small cell lung cancer (SCLC) appears to work better than standard chemotherapy in patients whose disease has recurred after initial chemotherapy. Findings from the international phase 3 clinical trial of tarlatamab (Imdelltra^®) were presented at ASCO by MSK scientist and thoracic medical oncologist Charles Rudin, MD, PhD. They were also published in the New England Journal of Medicine. 

Tarlatamab is a type of targeted immunotherapy called a bispecific T cell engager, or BiTE. It works by simultaneously latching on to tumor cells and T cells, a type of immune cell. The drug brings the two cell types close together, which stimulates the T cells to kill the adjacent cancer cells.  

Tarlatamab received accelerated approval from the U.S. Food and Drug Administration (FDA) in May 2024. Its full approval is contingent on subsequent trials to confirm its benefits. The new study specifically confirms the drug’s effectiveness in patients treated with only one prior therapy. Typically, the five-year survival rate for this class of patients has been under 10%. 

All 509 patients in the study had advanced SCLC that recurred or progressed after platinum-based chemotherapy. Some patients had also previously received immunotherapy drugs called checkpoint inhibitors.  

Half were randomized to receive tarlatamab; the other half received a current standard-of-care chemotherapy. 

Analysis showed that patients who received tarlatamab had a 40% reduction in the risk of death compared with those who got chemotherapy. This was true even for patients whose cancer had spread to the brain — an indicator of particularly aggressive disease. 

Importantly, the side effects for patients in the tarlatamab group were less severe than for those who got chemotherapy. Only 19% had to reduce the dose or interrupt treatment due to side effects, compared with 55% of patients in the chemotherapy group. Patients receiving tarlatamab reported significantly reduced symptoms of cough and shortness of breath compared with patients on chemotherapy.  

“We believe this study defines a better option than traditional chemotherapy for patients with recurrent small cell lung cancer,” Dr. Rudin says. “More broadly, the data support a new strategy — bispecific T cell engager immunotherapy — as an approach to treating lung cancer.” 

Oral targeted drug is effective against lung cancers with EGFR exon 20 insertion 

MSK thoracic medical oncologist and early drug development specialist Helena Yu, MD, presented promising preliminary findings at ASCO from an international phase 2 clinical trial that studied a new medicine called zipalertinib. This drug is a targeted therapy developed to treat non-small cell lung cancer (NSCLC) driven by a gene change called an EGFR exon 20 mutation. The exon 20 mutation represents about 10% of all EGFR mutations and is found in about 2% of NSCLC cases overall.  

Another drug called amivantamab (Rybrevant^®) was approved to treat cancers with this mutation in 2021, but it must be given as an IV infusion. By contrast, zipalertinib is a pill, which makes it easier for patients to take. 

The zipalertinib trial enrolled 244 patients with an average age of 65. All patients had an advanced NSCLC with the EGFR exon 20 mutation and had stopped responding to chemotherapy. Some patients had also received amivantamab, and the disease still progressed. They took zipalertinib pills twice a day. 

The researchers reported: 

• Among all patients in the study, 35% had significant shrinkage of their tumors. 
• For patients who had not previously received amivantamab, the response rate was even higher — 40%.
• Even for patients who had taken amivantamab, the response rate was 30%. This is important because it means patients could still benefit from zipalertinib after amivantamab stops working.
• The drug worked an average of about nine months before the cancer started growing again.
• Zipalertinib was effective even in patients whose cancer had spread to the brain. 

The side effects were mostly mild, and included anemia, rash and dry skin, fatigue, and gastrointestinal problems. 

“Zipalertinib appears to help many patients with this type of lung cancer, even when other treatments have stopped working,” Dr. Yu says. “Additionally, the side effects were mostly very manageable. This medicine could be an important new option for patients.” 

Giving osimertinib before surgery appears to benefit patients with EGFR+ lung cancer 

A targeted therapy called osimertinib (Tagrisso^®) is often given to patients after lung cancer surgery to prevent the cancer from coming back. A new clinical trial demonstrates that giving osimertinib before surgery with or without chemotherapy is better than giving chemotherapy alone. Findings from the international, randomized phase 3 were presented at ASCO by MSK thoracic medical oncologist Jamie Chaft, MD. 

Osimertinib is a pill that targets EGFR, a cancer-causing gene mutation found in many cases of non-small cell lung cancer (NSCLC). 

All 358 patients in the trial had stage 2 or stage 3 cancer with an EGFR mutation. They received treatment for at least nine weeks before having surgery.  

The researchers found that patients who got osimertinib with or without chemotherapy had a greater response than patients who received chemotherapy only: 

• 26% of patients who got osimertinib and chemotherapy together had their tumor shrink.
• 25% who got osimertinib alone had their tumor shrink.
• Only 2% who got chemotherapy alone had their tumor shrink. 

There were no unexpected side effects from osimertinib or the combination treatment. Among those receiving osimertinib, fewer patients were prohibited from surgery because their disease had progressed. 

The patients who got osimertinib did better than those who got chemotherapy no matter the patients’ age, sex, stage of disease, or the specific EGFR mutation in the tumor.  

“This study suggests that doctors should consider giving patients with EGFR-driven NSCLC osimertinib with or without chemotherapy before surgery,” Dr. Chaft says. “We plan to continue following these patients to determine the treatments’ impacts on recurrence rates and patterns.”