Enrollment Open for a Trial of Novel Drug-Chemo Combo for Lung Cancer

The phase 3 HARMONi clinical trial recently kicked off, evaluating the novel drug ivonescimab in combination with chemotherapy for patients with EGFR-mutant, locally advanced or metastatic non-squamous non-small cell lung cancer who experienced disease progression after treatment with a third-generation tyrosine kinase inhibitor (TKI) drug, such as Tagrisso (osimertinib).

According to a statement from Summit Therapeutics (the manufacturer of ivonescimab), the first patient has been dosed in HARMONi. Eligible patients can also still sign up for participation in the trial, which will take place in cancer centers in the United States, Canada, Europe and China.

Researchers plan on enrolling approximately 470 patients who will be randomly assigned to receive ivonescimab plus pemetrexed, followed by maintenance therapy with pemetrexed or plaebo with pemetrexed.

The main goals of the trial are to see if adding ivonescimab to chemotherapy improves two-year progression-free survival (time from treatment until death or disease worsening) and overall survival (time from treatment until death from any cause) rates. The researchers will also look at the percentage of patients whose disease responds to treatment, disease control rates, duration of response, time to response and side effects.

“Advanced or metastatic non-small cell lung cancer is such a devastating diagnosis for patients,” said Dr. Ian Anderson, a medical oncologist at Providence Medical Foundation, in Santa Rosa, California, who treated the first patient in HARMONi. “While we are making great strides as a medical community to improve the quality and duration of patients’ lives, there remains significant room for improvement in the treatment options available for these patients. In particular, for patients with an EGFR-mutated tumor whose tumor has progressed after their initial TKI therapy, there are limited options. We are particularly excited to evaluate the potential of ivonescimab in the HARMONi study to make a meaningful impact on the lives of these patients facing this difficult disease.”

Prior research showed that the standard treatment for non-small cell lung cancer may not be the best option for patients with an exon 20 insertion-mutant (a type of EGFR mutation) disease.

READ MORE: Standard Treatment May Not Be Best for Exon 20-Mutant Lung Cancer

Ivonescimab, which is also known as SMT12 and AK112, works in two ways. First, the drug is a PD-1 inhibitor, meaning that it blocks a protein that helps cancer cells hide from the immune system, thereby helping the immune system to recognize and attack cancer. Additionally, the drug also acts as a VEGF inhibitor, blocking the VEGF protein that stimulates the growth of new blood vessels. In doing so, the blood supply needed for tumor cells to grow becomes unavailable.

Based on the design of the drug, researchers predict that ivonescimab will mainly attack cancer cells, largely leaving healthy tissue alone, thereby reducing side effects.

“Team Summit is committed to our mission to improve the quality of lives and potential duration of lives of patients suffering from serious unmet medical needs, starting with lung cancer,” stated Dr. Maky Zanganeh, Co-CEO and president of Summit.

Researchers plan on completing the study in January 2026.

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