Amgen touts early combo data with Sanofi-backed KRAS partner in a bid to lift Lumakras' prospects

Amid pessimism from analysts about future sales, Amgen is touting early data for Lumakras as part of a combo against a host of cancers—including patients with KRAS-mutated non-small cell lung cancer (NSCLC). 

The data, released Tuesday as an early abstract from the upcoming World Conference on Lung Cancer, found that just more than a quarter of NSCLC patients treated with the combo experienced a partial response and nearly two-thirds had disease control. However, the efficacy jumped among four NSCLC patients that had never been treated with a KRAS-inhibitor. Among those patients, three experienced a partial response and all four had stable disease.

The company says dose expansion is "underway" to further define efficacy between the two groups. 

The findings were part of a phase 1 dose-escalation study testing Lumakras with Sanofi and Revolution Medicine’s SHP2 inhibitor. The two companies teamed up to co-develop the inhibitor, coined RMC-4630, four years ago. In November 2019, Revolution partnered with Amgen to test Lumakras (then known as AMG 510) with the SHP2 inhibitor. Now, industry watchers are getting first taste of how the two meds work together. 

The early trial recruited 21 cancer patients who had received at least two lines of prior treatment, 11 of whom had NSCLC. Six patients had colorectal cancer, while one had ovarian cancer and three had other solid tumors. Ten of the patients had been previously treated with a KRAS-inhibitor, most of whom received Lumakras. Two received Mirati Therapeutics’ clinical-stage competitor, adagrasib. 

In addition to the data in NSCLC patients, the early data tease hints at promise for the combo in other cancers. The patient with ovarian cancer achieved a partial response with an 81% reduction in tumor burden. Five out of six patients with colorectal cancer reached disease control, including one patient who had a 26% reduction in tumor burden. 

Investigators reported no life-threatening or disabling side effects, but grade 3 effects occurred in 29% of patients, ranging from high blood pressure to diarrhea. One patient dropped out of the trial due to a treatment-related side effects. 

The data are promising, albeit cherry-picked, but the outstanding question from an investor perspective remains: How do the findings impact future sales of Lumakras? A recent note from SVB Securities said the firm was lowering expectations for the drug, citing IQVIA prescription data, which found “2Q script growth seems to be trending well below levels needed to achieve consensus sales expectations.” 

For Amgen, adding to the pressure is Mirati's adagrasib. So far, durability data slightly favor the Amgen drug against the newcomer but a cancer specialist told Fierce Biotech at the American Society of Clinical Oncology annual meeting in June that the two meds are virtually identical. Regardless, Amgen continues to study Lumakras far and wide, with additional readouts coming over the next year across a number of indications, including a combo med between Lumakras and Boehringer Ingelheim’s SOS1 inhibitor.