AACR: 2 years in, Amgen fortifies Lumakras lung cancer data fortress for upcoming Mirati, Novartis KRAS battle

Amgen is busy building Lumakras’ case, taking advantage of an unexpectedly longer lead over KRAS rival Mirati Therapeutics.

Two years in, Lumakras’ data in previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC) continued to look solid. The first-in-class KRAS inhibitor shrunk tumors in 40.7% of patients, with the response lasting a median of 12.3 months, according to data presented at the American Association for Cancer Research (AACR) annual meeting.

The results improved upon data from the previous interim analysis, which showed a 37.1% response rate and 10-month duration recorded after 15.3 months of follow-up. The latest two-year update from the phase 1/2 CodeBreaK 100 trial also found that Lumakras takers went 6.3 months without their disease progressing and lived a median of 12.5 months.

“We want to ensure that with this prolonged follow-up, we continue to see this durability of response and this ultimate impact on overall survival, which was confirmed in this trial,” P.K. Morrow, M.D., Amgen’s vice president of global development, said in an interview with Fierce Pharma.

After two years, 32.5% of the patients were still alive, which the investigators noted compared favorably to historical data from Bristol Myers Squibb’s PD-1 inhibitor Opdivo in a broader, previously treated NSCLC population across two phase 3 trials.

Lumakras also conferred a “consistent benefit” across patient subgroups, including those with brain metastases and those whose tumors had low PD-L1 expression levels and STK11 co-mutations, Morrow said.

Of the 40 patients—out of a total 174—who lived at least 12 months without disease progression, nine had brain metastases, 28 had previously received both chemotherapy and PD-1/L1 immunotherapy and 16 tested negative for PD-L1.

Amgen hopes the new data will help Lumakras establish a stronger foothold as rival KRAS inhibitors draw near. Despite being the first drug approved against KRAS, a historically undruggable target, Lumakras suffered a rough start, which Amgen has attributed to COVID-19. After an FDA accelerated approval in May 2021, the drug reeled in $45 million in sales that fourth quarter, below Wall Street’s expectation of $62 million.

Amgen recently cut Lumakras’ addressable U.S. patient population in previously treated NSCLC to 7,000 from the previous 13,000 laid out last June, Piper Sandler analyst Christopher Raymond noted this February. The 7,000 actually covers only the second-line population, an Amgen spokesperson told Fierce Pharma. The later-line settings represent a one-time market opportunity during the initial launch phase, as new patients would start the med in the second line.

The focus remains on moving Lumakras to earlier treatment lines and expanding into other indications, and Amgen is exploring different combination strategies.

Lumakras’ confirmatory phase 3 trial, CodeBreaK 200, which compares the Amgen drug to chemotherapy docetaxel in previously treated KRAS G12-mutant NSCLC, is expected to read out in the second half of this year.

The timeline puts some pressure on rival Mirati’s KRAS inhibitor, adagrasib, after the FDA pushed back its decision date for a potential accelerated approval in the same NSCLC setting to Dec. 14. Adagrasib’s and Lumakras’ tumor response rates in NSCLC don’t look too different, but the Mirati drug’s early efficacy results in colorectal cancer appeared stronger than those the Amgen rival achieved in its own trial.

Meanwhile, Novartis is also reporting phase 1/2 NSCLC data for its KRAS candidate, coded JDQ443, at this year’s AACR meeting and is prepping to launch a phase 3 trial soon.

On the combination front, later this year Amgen will report initial data on Lumakras coupled with Merck & Co.’s PD-1 inhibitor, Keytruda, and with Revolution Medicines’ SHP2 inhibitor, RMC-4630.

Amgen recently signed on another SHP2 inhibitor, BridgeBio Pharma’s BBP-398, to pair with Lumakras. With two SHP2 partners, Amgen is looking at ways to “optimize the benefit-risk profile” of a Lumakras combo, Morrow said. Morrow wouldn’t say whether Amgen is moving forward with either of the two compounds but said the company is monitoring data, especially potential differences in safety profiles.