- A combination of Amgen’s targeted cancer drug Lumakras with one of two approved immunotherapies shrank lung tumors in a small clinical trial, but led to significant liver toxicity that limited patients’ ability to continue treatment.
- Amgen tested a range of Lumakras doses together with Merck & Co.’s Keytruda or Roche’s Tecentriq in the study, but adjusted the timing of administration in response to the safety data. Among the 58 patients with non-small cell lung cancer given the drugs, 17, or 29%, responded to treatment, which lasted a median of nearly 18 months.
- The highly anticipated results, released by Amgen Sunday and presented at the World Conference on Lung Cancer, fell short of expectations, and could curtail the potential of Lumakras, which in 2021 became the first drug approved to treat tumors driven to growth by mutations in a gene called KRAS.
Lumakras’ approval was a milestone in researchers’ efforts to target KRAS, which is frequently mutated in lung, colon and pancreatic cancers and for decades eluded attempts to block it with drugs.
But the drug’s approval was conditional, and limited to patients whose tumors were locally advanced or metastatic and who had already received at least one prior treatment. While testing had shown Lumakras led to responses nearly double of what typically would be expected from chemotherapy, only a third or so of patients benefited, leaving room for improvement.
Amgen has sought to do that through treatment combinations, hoping to find a regimen that might deliver higher response rates. But results so far have been mixed and, in the case of the immunotherapy pairing, have raised safety red flags.
Amgen executives had last week hinted at the difficulties of finding a balance between safety and higher efficacy, noting combinations with immunotherapy were “challenging.”
The trial results released Sunday showed treatment with Lumakras and either Keytruda or Tecentriq led to higher rates of severe treatment-related adverse reactions than did Lumakras alone. About half of patients given the drugs concurrently discontinued treatment with at least one medicine due to side effects, the data show.
The rates were reduced when Amgen switched to giving Lumakras by itself initially before adding in immunotherapy. Lower doses of Lumakras were also associated with less liver toxicity. Nearly all the cases resolved with steroids, treatment modification or discontinuation, Amgen said.
Dane Leone, an analyst at Raymond Jones, described the liver-related side effects as “substantial” in a note to clients, while Baird’s Brian Skorney said the data “make it all but impossible” to develop concurrent administration of Lumakras and immunotherapies like Keytruda and Tecentriq.
Amgen is continuing to study the drugs together in previously untreated patients with a modified dosing schedule.
But analysts are writing down their estimates for how widely used Lumakras might be in earlier lines of treatment.
“We think prospects for Lumakras to contend in [first-line non-small cell lung cancer] are now very low,” wrote Benjamin Burnett, an analyst at Stifel, in a note to clients.
Burnett views Amgen’s setback as an opportunity for Mirati Therapeutics, which is developing a similar drug to Lumakras and is also exploring immunotherapy combinations. In May, Mirati showed its drug, called adagrasib, delivered similar results as Lumakras in previously treated lung cancer patients, a group for which it hopes to win Food and Drug Administration approval later this year.
Shares in Mirati rose by as much as 10% in Monday morning trading, but later fell back to trade down by nearly 2%.
Both Amgen and Mirati are also studying their drugs head to head versus the chemotherapy docetaxel, trials which would serve as confirmatory studies for conditional approval. Results from Amgen’s are expected in the third quarter.