Dive Brief:
- A drug combination involving Gilead’s antibody medicine Trodelvy shrank or eliminated tumors in just over half of the lung cancer patients who received it in a closely watched Phase 2 trial, according to data released ahead of a medical meeting next month. The findings suggest Trodelvy, currently approved to treat breast and bladder cancers, may be active against lung tumors as well.
- The study, EVOKE-02, is testing several regimens of Trodelvy and Merck & Co.’s immunotherapy Keytruda with or without chemotherapy in patients newly diagnosed with advanced non-small cell lung cancer. Full results were inadvertently published Wednesday, weeks before the data will be presented at the World Conference on Lung Cancer.
- Wall Street analysts viewed the results as promising, but difficult to interpret, as they come from an “open label” study without a placebo or active comparator. The combination also had higher rates of side effects than the Keytruda and chemotherapy combination often used to treat front-line lung cancer, some analysts said.
Dive Insight:
Keytruda is on its way to becoming the world’s top-selling drug in part because of its widespread use in lung cancer, one of the most common forms of the disease. Gilead, as well as partners AstraZeneca and Daiichi Sankyo, are aiming to break into that market by proving their drugs can supply the chemotherapies typically used alongside Keytruda.
Each company is testing antibody drugs that target TROP2, a protein overexpressed in all types of lung cancer. There are currently no TROP2-targeting therapies for lung tumors; the companies are vying to see who can become the first. Their therapies are “antibody-drug conjugates,” which chemically link a targeting molecule to a tumor-killing toxin.
There are questions as to how meaningful the addition of a TROP2 therapy is, however. AstraZeneca and Daiichi reported success in a Phase 3 study in July, but haven’t presented details. They also disclosed some deaths in the trial from a type of lung scarring associated with their drug and others like it.
The Keytruda-chemotherapy combination has also set a high bar for would-be competitors to clear, as testing has shown a significant impact on survival. Jefferies analyst Akash Tewari wrote Thursday that developers may have to design trials with the right “biomarker strategy” to stand out.
The data released Wednesday don’t settle the debate surrounding the impact of TROP2-targeting drugs on lung cancer. Gilead has a Phase 3 trial underway that tests its drug against chemotherapy and should read out next year. Still, the findings do show Trodelvy “is adding some activity,” though its impact on survival and safety tradeoffs aren’t yet clear, wrote RBC Capital Markets analyst Brian Abrahams.
The study results come from two cohorts of patients with squamous and non-squamous disease. Both groups received Trodelvy and Keytruda. One study cohort enrolled patients with high levels of the protein PD-L1 — a marker associated with immunotherapy response — on their tumors. The other included patients with PD-L1 levels lower than 50%.
A snapshot of data from the trial was made available Wednesday via a study abstract published by the World Conference on Lung Cancer ahead of its meeting next month. But a more complete and up-to-date presentation was also briefly viewable before being taken down.
According to analysts who saw the full data, 69% of the 29 evaluable patients with high levels of PD-L1 responded to treatment. In those with lower levels of PD-L1, 44% of 32 evaluable patients responded. The combined response rate of the two groups was 56%.
More than half of treated patients experienced diarrhea — higher levels than what’s associated with the Keytruda-chemo combination — and 27% of patients had suppressed white blood cell counts. Three patients died from adverse events during treatment, although only one, a fatal case of sepsis, was considered related to the treatment.
The drug so far hasn’t been associated with the lung scarring condition, interstitial lung disease, that’s been observed in testing of AstraZeneca and Daiichi’s rival medicine.
“Overall, a good start, but some ways to go,” RBC’s Abrahams wrote.
