A new approach to a pressing challenge in lung cancer is delivering real-world benefits for patients as much as it advances science. A study led by Stanford Cancer Institute Clinical Trials Office medical director Joel Neal, MD, PhD, professor of medicine, tested a two-pronged attack on epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This approach recently received FDA approval, providing a critical new option for patients living with this form of cancer.
“EGFR-mutant lung cancer primarily affects patients without a smoking history. At Stanford, perhaps 30 to 40% of our clinic patients have non-small cell lung cancer with an EGFR-mutation,” Neal said. “So we're always eager to investigate new therapies for this cancer.”
The team paired amivantamab, a drug that blocks cancer growth signals from outside the cancer cell, with lazertinib, a pill-based targeted therapy that stops those signals from inside the cell. However, instead of the traditional method of administering amivantamab via a lengthy intravenous multi-hour infusion, the team gave the drug as a short subcutaneous, or under the skin, injection.
NSCLC is the most common type of lung cancer, and many tumors carry EGFR mutations that activate cell growth and proliferation. Drugs that disrupt the EGFR pathway can induce a strong response in EGFR-associated cancers, but tumor cells that are less sensitive can still continue to grow and lead to disease progression, making it paramount to discover strategies to overcome this resistance.
“Unfortunately, often, despite treatments that we use, many tumors eventually demonstrate resistance in the metastatic setting, and so we're trying to overcome that resistance by doing clinical trials that are more directed,” Neal said.
In this study, Neal and his team combined two complementary strategies. Amivantamab is a bispecific antibody, meaning it can bind to two targets simultaneously. In this case, it binds to EGFR and a receptor protein known as MET.
By attacking the cancer from outside of the cell, amivantamab helps shut down the signals the tumor uses to grow. Lazertinib, a third-generation EGFR tyrosine kinase inhibitor, acts intracellularly to directly block the EGFR pathway. A tyrosine kinase inhibitor is a targeted therapy that blocks the specific signals that tell cancer cells to grow and divide.
The team hoped that combining the two would deliver a one-two punch to the cancer: strike at the surface, then disable the internal signaling that fuels growth and resistance.
One of the study’s most noteworthy features was how amivantamab was administered. The traditional IV form requires full days in an infusion clinic, frequent visits during the early weeks of treatment, and can provoke infusion-related reactions like low blood pressure, fast heart rate, or rashes. The new subcutaneous formulation of amivantamab is given as a quick injection, taking less than five minutes to administer.
In this mode, patients receive the drug less often and with far less time spent in the clinic. The sub-Q version delivers the same anti-cancer effect with a more convenient and tolerable dosing schedule.
From a patient experience standpoint, the shift from intravenous to subcutaneous is a big deal. Neal emphasized that the shorter, simpler administration can translate into more time at home with family and friends and fewer disruptions to daily life. The data suggest that the subcutaneous formulation is as effective as the intravenous version.
I can't see any reason that we would continue intravenous amivantamab in anybody after this.
“What’s exciting is that we observed the efficacy to be the same or better than the intravenous version,” Neal said. “We want the best treatment with the lowest toxicity that's easiest for the patient. I can't see any reason that we would continue intravenous amivantamab in anybody after this.”
The key takeaway is that patients can achieve meaningful cancer control without bearing a heavier treatment burden.
FDA approval
The path to bringing this therapy into routine care involved a series of studies known as the Paloma trials. These trials collectively evaluated the subcutaneous amivantamab approach and its combination with lazertinib, leading to FDA approval.
The process was a collaboration among the drug sponsor, regulators, and multiple research centers, with Stanford contributing by enrolling patients and coordinating care in a real-world setting. The end result is a treatment option now integrated into standard practice at Stanford and, increasingly, across the United States.
A central thread running through this work is the vital role of patients and the care teams that support them. Neal strongly emphasized that progress depends on participants who participate in clinical trials, the clinical research coordinators who organize day-to-day activities, and the donors and philanthropists who sustain this work.
Neal’s work with subcutaneous amivantamab plus lazertinib is a significant step forward in lung cancer care. By pairing a precise, dual-action strategy against the EGFR pathway with a delivery method that respects patients’ time and comfort, this work advances the promise of precision medicine: powerful treatments that are also practical and person-centered.
