ASCO24: Amgen's Lumakras combo raises OS hopes in mCRC

2024-06-03

临床结果ASCO会议临床3期加速审批上市批准

Combining Amgen's KRAS G12C inhibitor KRAS G12C inhibitor Lumakras (sotorasib) with the EGFR antibody Vectibix (panitumumab) showed a promising overall survival (OS) trend in patients with chemorefractory metastatic colorectal cancer (mCRC) harbouring the KRAS G12C mutation, according to data from the CodeBreaK 300 trial presented Monday at the American Society of Clinical Oncology (ASCO) annual meeting.

The late-breaking presentation provided the final OS analysis from the Phase III study, which had previously met its primary endpoint of improved progression-free survival (PFS) at both tested doses of Lumakras compared to investigator's choice of therapy. Those PFS results were reported last December at the European Society for Medical Oncology (ESMO) conference.

The study included 160 patients randomly assigned to receive Lumakras at doses of either 960mg or 240mg together with Vectibix, or investigator's choice of treatment consisting of either trifluridine/tipiracil or Bayer's Stivarga (regorafenib).

Trial not powered to show OS benefit

In the ASCO update, researchers reported that 82 deaths had occurred as of the December 18 cut-off, after a median follow-up of 13.6 months; 24 were in the higher-dose Lumakras group, 28 in the lower-dose group, and 30 in the investigator's choice arm.

Median OS was not reached with Lumakras 960mg and was 11.9 months for the 240mg dose and 10.3 months for those who received investigator's choice of therapy. The hazard ratios for OS favoured the Lumakras combinations, with a HR of 0.70 for the 960mg dose and 0.83 for the 240mg dose, both in comparison to investigator's choice.

"While CodeBreaK 300 was not powered to detect a statistically significant difference in OS, the study showed a trend toward improved OS" for patients randomised to the higher dose of Lumakras plus Vectibix, researchers concluded.

Other key efficacy data showed a 30.2% objective response rate (ORR) for the higher Lumakras dose combination, including one complete response (CR) and 15 partial responses (PRs). The median duration of response was 10.1 months in this arm. The disease control rate was also highest at 71.7% with the 960mg combination. There was 1 CR and 3 PRs at the lower dose, and 1 PR for investigator's choice.

Criticism of higher dose

Amgen is testing the lower 240mg dose of Lumakras once daily due to the drug's non-linear pharmacokinetic properties. However, the company's decision to maintain the higher 960mg dose in its approved labeling has drawn criticism from US Senator Richard Durbin, who accused Amgen of "putting profits before patients" and disregarding concerns over harsh side effects.

Lumakras won accelerated approval from the FDA in 2021 for KRAS-mutated non-small-cell lung cancer (NSCLC), although the agency recently rejected Amgen's bid for full approval.

In response to Durbin's criticism last month, the company stated that "based on data from several clinical trials across numerous cancer types, as well as real-world evidence, we are confident that patients with lung cancer are benefiting from the once-daily 960mg dose of Lumakras."

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