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After Amgen's stumble, BMS touts KRAS confirmatory trial win for newly bought Krazati

2024-03-29

临床3期并购临床结果上市批准加速审批

Krazati came to Bristol Myers Squibb as part of the New Jersey pharma's recent acquisition of Mirati Therapeutics.

Bristol Myers SqBristol Myers Squibbto overtake Amgen as the KRAS leader in lung cancer after Mirati Therapeuticsval’s FDA setback with a positive confirmatory trial readout.

Bristol Myers Squibbcantly reduced the risk of tAmgenprogression or death colung cancer chemotherapy in patients with pretreated KRAS G12C-mutated non-small cell lung cancer (NSCLC), the company said Thursday. The KRAS inhibitor came to the New Jersey pharma as part of its recent acquisition of Mirati Therapeutics.

The aKrazatint was made by a blinded central retumorcommittee of the pivotal phase 3 KRYSTAL-12 study, which serves as the confirKRAS G12C-mutated non-small cell lung cancer (NSCLC)KRAS G12Cial for Krazati’s accelerated approval as a second-line therapy. BMS said itKRAS inhibitor KRASinishing a full evaluation of the data and will share results with regulators.Mirati Therapeutics

Besides declaring that the trial met its primary endpoint of progression-free survival, the independent data reviewers noted that Krazati was bettKrazati chemo at shrinking tumors, which was one of the trial’s secondary endpoints. The improvements on both endpoints were statistically significant and clinically meaningful, according to BMS.

The trial remains ongoing to evaluate whether Krazati can extend patients’ lives. BMS didn’t specify which direction Krazati’s surKrazatiutcomes are trending right now. Progtumorsn-free survival has typically been an approval-worthy endpoint in second-line NSCLC, unless there’s a negative trend in overall survival.

As for Amgen, the California drugmaker recentlKrazatied for full approval of its first-to-market KRAS inhibitor, Lumakras, based on progression-free survival data from the phase 3 CodeBreaK 200 trial. The study would have served its purpose had it been doneNSCLCerly. But the FDA figured its results couldn’t be reliably interpreted, and a group of external advisers agreed.

The ageAmgennd its advisory committee experts voiced concerns about disproportionate patient dropKRAS inhibitor KRASrates betweeLumakraso trial arms in Lumakras’ CodeBreaK 200 study as well as a bias for investigators to be more likely to call tumor progression early for patients on chemo sFDAhat they could cross over to receive Lumakras.

Both problems were chalked up to the enthusiasm around Lumakras as the first FDA-approved KRAS inhibitor.tumor Lumakras

By comparison, Krazati’s KRYSTAL-12 requires confirmatiLumakrasa blinded central review toKRAS inhibitor KRASermine tumor progression before crossover.

Despite the compromised trial results, the FDA has let Lumakras stay on the market while Amgen runs atumorr confirmatory trial to be completed no later than February 2028. The recently launched phase 3 CodeBreaK 202 trial is comparing Lumakras against Merck’s Keytruda in their respective combinations with chemotherapy for patients with newly diagnosed, advanced, PD-L1-negative, KRAS G12C-positive nonsquamous NSCLC.

Lumakras’ setback gives Krazati an opportunFDA to catchLumakrasore the BMS buyout, KrazatAmgenthe third quarter posted $16.4 million in sales, coming in below analysts’ expectations. Lumakras generated $52 million sales during the sameLumakras Merck Keytruda PD-L1-negative KRAS G12C-positive nonsquamous NSCLC KRAS G12C

BMS' Krazati also appears to hold more potential in the first-line setting. While AKrazatis forced to combine Lumakras with chemo alone, a better liver toxicity profile has allowed BMLumakrasr Krazati with drugs in the PD-1 inhibitor class. A phase 3 trial is testing the Krazati-Keytruda combo in first-line KRAS G12C-mutated PD-L1-high NSCLC. And the company expects phase 2 results this year to guide its development path in PD-L1-low disease.

Both Krazati Amgen are also gunning for approvals in colorectal cancer, which is aAmgenler market than NSCLC. Lumakrascently reported that Lumakras, at its currently approved 960-mg dose and usKrazatiombination with VecPD-1x, extended the median progression-free survival to 5.6 months versus 2.2 months for sKRAS G12C-mutated KRAS G12CreatmentsPD-L1-high NSCLC PD-L1-hights with chemo-refractory KRAS G12C colorectal cancer. The result came from the phase 3 CodeBreaK 300 trial.

A regBMStory Amgenssion based on the study was plannecolorectal cancerlf of 2024, Amgen said during itsNSCLCthAmgenter report. The company Lumakras also launched a phase 3 trial for Lumakras in combination with VectiVectibixchemo in first-line colorectal cancer.chemo-refractory KRAS G12C colorectal cancer

For its part, BMS has the phase 3 KRYSTAL-10 study for Krazati and Eli Lilly’s ErbAmgenin second-line colorectal cancer, with a readout expected this year.Lumakras Vectibix colorectal cancer