{"id":59578,"date":"2024-06-22T04:04:39","date_gmt":"2024-06-22T02:04:39","guid":{"rendered":"https:\/\/pharma-trend.com\/en\/bristol-myers-squibb-announces-u-s-fda-accelerated-approval-of-krazati-adagrasib-in-combination-with-cetuximab-for-adult-patients-with-previously-treated-kras-g12c-mutated-locally-advanced-or\/"},"modified":"2024-06-22T04:04:39","modified_gmt":"2024-06-22T02:04:39","slug":"bristol-myers-squibb-announces-u-s-fda-accelerated-approval-of-krazati-adagrasib-in-combination-with-cetuximab-for-adult-patients-with-previously-treated-kras-g12c-mutated-locally-advanced-or","status":"publish","type":"post","link":"https:\/\/pharma-trend.com\/en\/bristol-myers-squibb-announces-u-s-fda-accelerated-approval-of-krazati-adagrasib-in-combination-with-cetuximab-for-adult-patients-with-previously-treated-kras-g12c-mutated-locally-advanced-or\/","title":{"rendered":"Bristol Myers Squibb Announces U.S. FDA Accelerated Approval of KRAZATI\u00ae (adagrasib) in Combination with Cetuximab for Adult Patients with Previously Treated KRAS G12C-Mutated Locally Advanced or Metastatic Colorectal Cancer (CRC)"},"content":{"rendered":"
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\nApproval based on results from the Phase 1\/2 KRYSTAL-1 study where KRAZATI in combination<\/i> with cetuximab showed an objective response rate of 34% in pretreated patients with locally advanced or metastatic CRC harboring a KRASG12C<\/sup> mutation1<\/sup><\/i><\/p>\n

\nSecond FDA approval for KRAZATI – reinforcing its potential across tumor types<\/i><\/p>\n

PRINCETON, N.J.–(BUSINESS WIRE)–$BMY<\/a> #BristolMyersSquibb<\/a>—Bristol Myers Squibb<\/a>\u00a0(NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for KRAZATI<\/i>\u00ae<\/sup> (adagrasib) in combination with cetuximab as a targeted treatment option for adult patients with KRASG12C<\/sup><\/i>-mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) results. Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.\u00a0<\/p>\n

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\n\u201cCRC with a KRASG12C<\/sup><\/i> <\/sup>mutation occurs in approximately 3-4% of CRC patients and has historically been challenging to treat,\u201d2<\/sup> said Rona Yaeger, MD, Gastrointestinal Oncologist & Early Drug Development Specialist, Memorial Sloan Kettering Cancer Center. \u201cThe FDA approval of KRAZATI<\/i> combined with cetuximab now provides a new treatment option to these patients when their tumors do not respond well to prior therapies.\u201d<\/p>\n

\nThe approval is based on results from cohorts of the Phase 1\/2 KRYSTAL-1 open-label study which evaluated KRAZATI<\/i> (600 mg tablets administered orally twice daily) in combination with cetuximab in 94 patients with heavily pretreated CRC harboring a KRASG12C<\/sup><\/i> mutation. The study met its primary endpoint, with a confirmed ORR of 34% (n=94, 95% CI: 25-45) for KRAZATI<\/i> with cetuximab, all of which were partial responses. The median DOR, one of the secondary endpoints, was 5.8 months (95% CI: 4.2-7.6).1<\/sup> Current late-line standard of care options result in limited response rates (ORR 1-6%) after progression on chemotherapy \u00b1 VEGF\/VEGFR inhibitors.3,4<\/sup><\/p>\n

\nKRAZATI<\/i> is associated with the following Warnings & Precautions: Gastrointestinal adverse reactions including diarrhea, nausea, and vomiting, QTc interval prolongation, hepatotoxicity, and interstitial lung disease (ILD)\/pneumonitis.1<\/sup> Please see Important Safety Information below.<\/p>\n

\n\u201cToday\u2019s approval of KRAZATI<\/i> in CRC is the second in the U.S. for this therapy and the first for BMS’ recently expanded oncology portfolio. This is an important milestone for BMS and the patients we serve as we deliver on our commitment to provide innovative medicines for cancer,\u201d said Wendy Short Bartie, senior vice president, U.S. Oncology and Hematology at Bristol Myers Squibb. \u201cWe are proud to make KRAZATI<\/i> – the first KRASG12C<\/sup><\/i> inhibitor to be FDA approved beyond non-small cell lung cancer – available to CRC patients, and look forward to further evaluating KRAZATI <\/i>through our ongoing development program.\u201d<\/p>\n

\nIn 2022, the FDA granted breakthrough therapy designation for KRAZATI<\/i> in combination with cetuximab for patients with KRASG12C<\/sup><\/i>-mutated advanced CRC whose cancer has progressed following prior treatment with certain chemotherapy and an anti-VEGF therapy.<\/p>\n

\nKRAZATI<\/i> is an irreversible inhibitor of KRASG12C<\/sup><\/i> with a long half-life (23 hours), dose-dependent pharmacokinetics (PK), and central nervous system (CNS) penetration, which, in combination with cetuximab may enhance inhibition of KRAS-dependent signaling or overcome adaptive feedback.<\/p>\n

\nThe company partnered with QIAGEN to develop a tissue-based companion diagnostic (CDx) for KRAZATI<\/i> that is now available.<\/p>\n

\nKRAZATI<\/i> is a registered trademark of Mirati Therapeutics, Inc., a Bristol Myers Squibb company.<\/p>\n

\nAbout KRYSTAL-1<\/span><\/b><\/p>\n

\nKRYSTAL-1 is an open-label, multicenter, multiple expansion cohort Phase 1\/2 trial to determine the safety and efficacy of KRAZATI<\/i> in patients with advanced colorectal cancer (CRC) that harbor a KRASG12C<\/sup> <\/i>mutation. The primary endpoint for the Phase 2 cohort of the KRYSTAL-1 study was objective response rate (ORR). Secondary endpoints included duration of response (DOR).<\/p>\n

\nThe KRYSTAL-1 study was funded by Mirati Therapeutics, Inc., a Bristol Myers Squibb company.<\/p>\n

\nSelect Safety Profile from KRYSTAL-1<\/span><\/b><\/p>\n

\nThe safety profile for KRAZATI<\/i> plus cetuximab was evaluated in patients with KRASG12C<\/sup><\/i>-mutated, locally advanced or metastatic CRC, and is consistent with previous reports and known safety profile of each drug individually. Serious adverse reactions occurred in 30% of 94 patients who received KRAZATI<\/i> in combination with cetuximab. The most common adverse reactions (\u226520%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, dizziness, cough, constipation, and peripheral neuropathy.1<\/sup><\/p>\n

\nAbout Colorectal Cancer<\/span><\/b><\/p>\n

\nColorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body\u2019s digestive, or gastrointestinal, system.5<\/sup> CRC is the third most commonly diagnosed cancer in the world.6<\/sup> In 2024, it is estimated that there will be approximately 106,590 new cases of the disease in the U.S.; it is the second leading cause of cancer-related deaths in the U.S. among men and women combined.7<\/sup><\/p>\n

\nKRAS is the most frequently mutated oncogene in human cancer and is one that drives oncogenesis in up to 50% of patients with CRC.2<\/sup> The KRASG12C<\/sup><\/i> <\/sup>mutation occurs in approximately 3-4% of CRC cases.2<\/sup><\/p>\n

\nAbout KRAZATI<\/i>\u00ae<\/sup> (adagrasib)<\/span><\/b><\/p>\n

\nKRAZATI<\/i> (adagrasib) is a highly selective and potent oral small-molecule inhibitor of KRASG12C<\/sup><\/i> that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12<\/sup><\/i>C<\/sup>-mutated cancers, as the KRASG12C<\/sup><\/i> protein regenerates every 24-48 hours.8<\/sup> KRASG12C<\/sup><\/i> mutations act as oncogenic drivers and occur in approximately 14% of non-small cell lung cancer (NSCLC; adenocarcinoma) and 3% of several other cancers.9,10<\/sup><\/p>\n

\nIn 2022, KRAZATI<\/i> was granted accelerated approval for treatment of adult patients with KRASG12C<\/sup><\/i>-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.<\/p>\n

\nKRAZATI<\/i> continues to be evaluated as a monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C<\/sup><\/i>-mutated solid tumors, including NSCLC and CRC.<\/p>\n

\nPlease see U.S. Full Prescribing Information for KRAZATI<\/i><\/a>.<\/p>\n

\nINDICATIONS<\/span><\/b><\/p>\n

\nKRAZATI<\/i> in combination with cetuximab is indicated for the treatment of adult patients with KRASG12C<\/sup><\/i>-mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.<\/p>\n

\nKRAZATI<\/i>, as a single agent, is indicated for the treatment of adult patients with KRASG12C<\/sup><\/i>-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.<\/p>\n

\nThese indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of a clinical benefit in confirmatory trials.<\/p>\n

\nIMPORTANT SAFETY INFORMATION<\/span><\/b><\/p>\n

\nIMPORTANT SAFETY INFORMATION<\/b><\/p>\n

\nWARNINGS AND PRECAUTIONS<\/b><\/p>\n

\nGastrointestinal Adverse Reactions<\/b><\/p>\n