Clinical Trials

New Clinical Trial Evaluating Ivonescimab in Advanced NSCLC

By September 10, 2026September 14th, 2026No Comments

A new clinical trial at Massachusetts General Hospital is testing whether a dual-action immunotherapy can help lung cancer patients whose targeted therapy has stopped working.

A new Phase II clinical trial at Massachusetts General Hospital is evaluating ivonescimab (AK112), a novel immunotherapy, in patients with advanced NSCLC whose tumors harbor actionable genomic alterations. The study is led by Jessica Lin, M.D., at Massachusetts General Hospital, who is the Principal Investigator and responsible party for the trial. Dr. Lin is a member of The Happy Lungs Project’s Scientific Advisory Board and one of the leaders of the recently published RETgistry study.

Key Takeaways

A Phase II trial is testing ivonescimab, a new immunotherapy, alone or combined with chemotherapy, in advanced NSCLC including RET patients
Led by Dr. Jessica Lin at Mass General - leader of the RETgistry study and a member of HLP's Scientific Advisory Board
The drug works by targeting two pathways at once (PD-1 and VEGF-A), making it particularly interesting in tumors where VEGF signaling may contribute to tumor growth and resistance
Open to NSCLC patients who have already tried targeted therapy
The study is open at Mass General and the treatment is given intravenously every three weeks for up to 24 months

Ivonescimab is designed to target two pathways at once: PD-1 and VEGF-A. By combining immune activation with inhibition of tumor blood-vessel growth, the approach aims to help the immune system better recognize and attack cancer cells.

Importantly, this study is enrolling patients with several actionable oncogenic drivers, including RET fusions. While immunotherapy alone has historically shown limited activity in many oncogene-driven lung cancers, ivonescimab’s dual mechanism targets both PD-1 and VEGF-A, making it particularly interesting in tumors where VEGF signaling may contribute to tumor growth, metastasis, and resistance mechanisms.

The trial includes two treatment cohorts:

  • Ivonescimab alone: for patients with actionable genomic alterations who have previously received targeted therapy and platinum/pemetrexed chemotherapy. 
  • Ivonescimab + carboplatin/pemetrexed: for patients with actionable genomic alterations who have received prior targeted therapy but have not previously received chemotherapy. 

Treatment is given intravenously every three weeks for up to 24 months, depending on response and tolerability. The study plans to enroll approximately 46 patients.

Why this trial matters: As patients with actionable alterations such as RET, ALK, ROS1, and others eventually develop resistance to targeted therapies, finding effective treatment strategies after progression remains an important unmet need. This study is exploring whether a next-generation immunotherapy, alone or combined with chemotherapy, can provide another treatment option for these patients.

 

Additional Resources

ClinicalTrials.gov: NCT07405190 — currently recruiting at Massachusetts General Hospital. View the trial on ClinicalTrials.gov

More info here: https://www.dana-farber.org/clinical-trials/26-015

And view the study overview here.

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