New study results for Amgen's KRAS-blocking cancer drug support the therapy's promise as a major advance in treating tumors spurred by a mutant gene that's known as the field's "white whale."
Yet the data, announced Sunday at the World Conference on Lung Cancer in Barcelona, Spain, also hint at the drug's limits, leaving an opportunity for the handful of drugmakers advancing rival treatments.
Among 13 lung cancer patients treated with the highest dose of AMG 510, as the drug's called, seven responded to treatment and saw their tumors shrink. That 54% response rate compares to the 100% mark posted by Amgen in June from the first three patients treated at that dose.
Two patients who appeared to benefit from treatment later relapsed, however, and six of the 10 patients treated since Amgen's first disclosure haven't responded, although their disease is considered stable.
Study participants were sick, with 85% having received treatment with more than two previous cancer therapies. And seeing responses at all is noteworthy for tumors spurred by alterations in the KRAS gene, which has for decades proved resistant to efforts at targeting it.
Researchers and pharma companies have kept trying, because the genetic signature is found in many lung, colorectal and pancreatic tumors. Amgen's drug aims at a specific KRAS mutation known as G12C estimated to be present in 13% of non-small cell lung cancers and between 3% and 5% of colorectal cancers.
"The data provides clear evidence that the drug has significant anti-tumor activity in the G12C population, the first targeted therapy that I think can make this claim," said John Heymach, an oncologist at The University of Texas MD Anderson Cancer Center, in response to questions from BioPharma Dive. MD Anderson is involved in the expansion phase of Amgen's study, and Heymach is collaborating on that effort.
Heymach cautioned that it's not yet clear how durable responses will be, but noted that response rates to chemotherapy and immunotherapy in this setting range between 10% and 20%.
Among all patients treated with AMG 510 and evaluable for efficacy, 11 of 23, or 48%, had their tumors decrease in size. (The trial also tested three lower doses than the 960 mg regimen chosen to advance into further testing.) Some patients treated early on in the trial are still in response six to 10 months later.
Importantly for AMG 510's potential, few serious treatment-related side effects were reported and no adverse events led to study discontinuation by participants. Twenty-seven of the 34 lung cancer patients who've received AMG 510 to date remain on treatment.
Expectations were extremely high for AMG 510 going into the World Lung Conference, raising the risk of disappointment from investors hoping to see a response rate at the higher end of the predicted 50% to 70% range by analysts for the 960 mg dose.
Investors will get another look at AMG 510 later this month, when Amgen will present updated results for AMG 510 in colorectal cancers.
The company has moved quickly to advance the drug and has begun enrolling patients into an expansion phase that combines AMG 510 treatment with PD-1-blocking immunotherapy. A Phase 2 study that could support submission to the Food and Drug Administration for approval is also under way.
"That's enrolling quite briskly," said Amgen's R&D chief David Reese on a Sunday conference call. "We've seen tremendous investigator enthusiasm around the world." Reese suggested data from that study could be available by next year.
While that trial will look at AMG 510 monotherapy, combinations will also be an important part of Amgen's development, given the potential for tumors to develop treatment resistance.
"I wouldn’t be so naive to think that after everything we’ve learned about targeted therapy oncology that resistance will not emerge at least in some tumors," said Reese at an investor conference in June. "That's, I think, a critical question that we need to address in terms of development going forward."
Roy Herbst, chief of medical oncology at the Yale Cancer Center, also puts treatment resistance among his list of still unanswered questions.
"My biggest concern with KRAS is there are many redundant pathways," he said in an interview. Tumors, in other words, may rely on other genetic growth drivers if mutant KRAS signaling is blocked.
While Amgen's out in front with its KRAS efforts, others aren't too far behind.
Small biotech Mirati Therapeutics is expected to present initial data for a rival KRAS-blocking drug later this fall, and others are moving forward with Phase 1 testing.
"Are there room for others in the space? Absolutely," said Herbst. "It's not a home run yet."