Your treatment journey for non-small-cell lung cancer (NSCLC) may vary from that of others with the same diagnosis. But you’ll likely start with some of the same treatments. You’ll have lots of options, especially if your cancer cells have an epidermal growth factor receptor (EGFR) mutation.
Having EGFR-mutated NSCLC is actually good news. That’s because your doctor will likely suggest a combination treatment.
“Treatment combinations have improved the outlook for EGFR-mutated NSCLC,” says Pasi Jänne, MD, a medical oncologist at the Dana-Farber Cancer Institute in Boston.
Understanding more about the lung cancer drug pipeline — which new medicines are being tested — can better prepare you for what’s next. You may also feel empowered to ask questions and make shared decisions with your cancer care team.
Learn more about combining medications for lung cancer, new therapies, and what type of treatments are on the horizon for EGFR-mutated NSCLC.
Progress in Treating EGFR-Mutated NSCLC
Targeted therapies can block the EGFR signal to slow or stop your cancer from growing. There are options that treat:
- The two most common EGFR mutations, called EGFR exon 19 deletions and L858R point mutations
- The most common NSCLC mutation that causes treatment resistance, called the EGFR T790M mutation
Combined treatment for EGFR-mutated NSCLC
Your doctor may suggest an EGFR inhibitor, sometimes called a tyrosine kinase inhibitor (TKI), added to chemotherapy or a bispecific antibody — a treatment that can grab two different targets at the same time. Combining medicines can help your:
- Treatment last longer
- Prevent the cancer cells from changing the DNA code to resist the treatment
- Delay a second cancer cell DNA change, such as a MET mutation
“Everyone can benefit from getting a combination compared to just one medicine — which was the prior way to treat this disease,” Jänne says.
What’s the Treatment Pipeline?
The treatment pipeline refers to the way scientists, doctors, and people with lung cancer work together to test new medicines. Before getting approved, the new treatment goes through many steps to make sure it is safe and works to kill lung cancer.
Lung cancer is smart, and it often finds ways to grow despite your treatment. This can make treating lung cancer, even with breakthrough treatments, a challenge in the long run. “Even with these therapies, we’re unfortunately not curing anyone with advanced EGFR-mutant lung cancer,” Jänne says. “So, there remains a need to identify new treatment approaches.”
What’s in the pipeline for EGFR-mutated NSCLC?
Researchers are working to develop new medicines that can treat:
- Rare EGFR mutations
- Common mutations more effectively
Many new medicines are being tested, such as:
- Fourth-generation EGFR inhibitors or TKIs
- Antibody-drug conjugates (ADCs)
- Bispecific antibodies
“There’s a lot of enthusiasm and interest in developing new therapies for [people with EGFR-mutated NSCLC],” Jänne says. “This space is rapidly evolving over time and evolving in a good way, as new therapies are being tested alone or in combination.”
What are Next-Generation EGFR Inhibitors?
The next-generation EGFR inhibitors might improve outcomes. These are sometimes called fourth-generation TKIs. The current EGFR inhibitors work to:
- Destroy any lung cancer cells sensitive to treatment
- Leave behind any resistant cancer cells
Over time, any resistant lung cancer cells left behind can grow or spread to new places inside your body. To help prevent resistance and spread of cancer cells, next-generation EGFR inhibitors might silence the EGFR signal permanently.
“There are a few different companies working on these drugs,” says Collin Blakely, MD, a medical oncologist who specializes in lung cancer at the University of California, San Francisco (UCSF). “The idea is that they’re potentially even more specific for EGFR and have better binding activity or can target resistance mechanisms that come up.”
JIN-A02 for EGFR-mutated NSCLC
This novel next-generation EGFR inhibitor targets mutated EGFR signals in NSCLC, including two common mutations called C797S and T790M. These mutations are a major cause of treatment resistance after taking other standard EGFR inhibitors.
Here are some things to know about:
How do you take it? JIN-A02 comes in a pill form that people in the studies take by mouth once a day.
Who is JIN-A02 for? It’s being studied for people with EGFR-resistant mutations whose disease has progressed after taking an EGFR inhibitor or chemotherapy.
Where is JIN-A02 in the pipeline? A phase 1/2 clinical trial is currently underway to test if the medicine works and is safe.
How well does it work? It’s still early, but studies suggest that this medicine can cross into the brain (called the blood-brain barrier) to treat NSCLC spots in the brain. More study is needed to know how well it works to help improve outcomes or survival.
How Next-Generation Antibody-Drug Conjugates (ADCs) Work
ADCs are linked to another medicine, most often a chemotherapy drug, to deliver it straight to your cancer cells. This helps kill cancer cells while sparing healthy ones. There are some ADCs already approved to treat lung cancer, including:
- Datopotamab deruxtecan-dlnk (Datroway), which targets a protein called TROP-2
- Telisotuzumab vedotin (Emrelis), which targets MET mutations in lung cancer cells
- Trastuzumab deruxtecan (Enhertu), which targets HER2-mutated NSCLC
Patritumab deruxtecan (HER3-Dxd)
This ADC works to lower the mutated signal called HER3. Lung cancer cells make more of (overexpress) this mutated signal, which is commonly found in EGFR-mutated lung cancer.
How do you take it? You receive this ADC by IV infusion at regular intervals.
Who is patritumab deruxtecan for? The ADC is being studied for people with advanced EGFR-mutated NSCLC and certain mutations, such as exon 19 deletions and L858R, whose disease has progressed after another therapy.
Where is patritumab deruxtecan in the pipeline? This ADC made it into phase 3 clinical trials following promising results in earlier studies.
How well does it work? Studies are looking at adding patritumab deruxtecan with osimertinib (Tagrisso). The ADC works by targeting HER3, directly delivering chemotherapy to kill lung cancer cells.
Sacituzumab tirumotecan (sac-TMT)
In advanced EGFR-mutated NSCLC, this ADC targets a protein on cancer cells called TROP2, which may help kill lung cancer cells.
How do you take it? Clinical studies are testing a fixed dose given by infusion every few weeks.
Who is it for? People with advanced EGFR-mutated NSCLC with certain EGFR mutations or other common NSCLC gene changes are enrolled in trials.
Where is it in the pipeline? Testing in a phase 3 trial compared this ADC to chemotherapy in people who already had treatment for advanced EGFR-mutated NSCLC or whose cancer has spread to other body parts. Studies showed that sac-TMT may improve overall survival in EGFR-mutated NSCLC after earlier treatments.
How well does it work? It’s still early, but compared to standard treatment with chemotherapy, this ADC might help you live longer.
Telisotuzumab vedotin (Emrelis) for EGFR mutations
This ADC targets a protein called MET, delivering chemotherapy to block microtubules, which stops lung tumor growth. The FDA approved Emrelis to treat NSCLC with MET mutations, but it’s being studied to treat EGFR mutations.
How do you take it? You receive this ADC through IV infusion every two weeks.
Who is it for? It’s currently approved for NSCLC with high levels of MET protein. Emrelis is also in clinical testing for EGFR-mutated NSCLC with MET mutations. If you aren’t sure, ask your doctor if this ADC is right for you.
Where is it in the pipeline? It’s already approved for MET-mutated NSCLC, but studies are ongoing for people with EGFR mutations, too. A phase 2 clinical trial, which combines telisotuzumab vedotin with osimertinib for NSCLC with an EGFR-mutation that has progressed, is ongoing.
How well does it work? More study is needed to know how this ADC works and if adding it to other treatments such as EGFR inhibitors can help improve outcomes. The FDA already says the medicine is safe and effective to treat NSCLC with high levels of MET.
What Are Bispecific Antibodies for EGFR-Mutated NSCLC?
This medicine can grab two different targets, so it’s called a bispecific antibody. The already approved ones to treat NSCLC include:
- Amivantamab (Rybrevant) for certain changes in EGFR and MET, sometimes combined with chemotherapy or another EGFR-targeted medicine called lazertinib (Lazcluze)
- Zenocutuzumab (Bizengri) for NRG1 gene fusions in lung cancer
Ivonescimab (AK112)
This bispecific antibody targets two proteins:
- PD-1, which plays an important role in using immunotherapy medicines against cancer
- VEGF, which is a protein that normally helps new blood vessels grow
How do you take it? In studies, people take ivonescimab as an infusion every three weeks.
Who is it for? It is for people with EGFR-mutated NSCLC in whom earlier treatments didn’t work and for certain other cancers.
Where is it in the pipeline? A phase 1/2 trial is ongoing to test ivonescimab with datopotamab deruxtecan or osimertinib in people with EGFR-positive lung cancer.
How well does it work? Studies are still in the early phases, so it’s too soon to know how well AK112 works against NSCLC compared to other options.
MCLA-129
This bispecific antibody targets EGFR and MET mutations.
How do you take it? In early trials, people got this medicine as an infusion every two weeks.
Who is it for? Researchers are testing MCLA-129 in trials alone or in combination for people with advanced NSCLC and other types of solid cancers.
Where is it in the pipeline? An early phase 1/2 clinical trial is underway in the U.S.
How well does it work? It’s too soon to know how well this treatment works for EGFR-mutated NSCLC.
What to Expect
The landscape for EGFR-mutated NSCLC treatment has changed quickly with new medicines and combination therapies. Scientists continue to make more drugs, so your doctor may offer many new ways to treat your lung cancer.
In the future, hopefully, lung cancer will be treated earlier. “I think we’ll be moving combinations sooner and sooner in the disease course for patients,” Blakely says. “I do think the strategy of trying to use our best therapies earlier tends to result in the biggest long-term gains for patients.”
